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=20251203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel in-frame duplication variant of SOD1 in a Japanese family with familial amyotrophic lateral sclerosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: To analyze the cases of a family with a novel in-frame duplication variant (NM_000454.5:c.357_357 + 2dup, p.Val120dup) of SOD1 and a structural model of the mutated SOD1 protein. Methods: The clinical profiles of three patients in the family were analyzed, including the neuropathological findings of the proband’s mother. Genetic analyses were conducted for three patients. cDNA and in silico structural analyses were performed to evaluate the effects of duplication variants on the structure of SOD1. Results: The clinical features of the patients included predominant involvement of the lower motor neurons, asymmetric onset of motor symptoms in the lower limbs, and a relatively rapid progression of muscular weakness and respiratory insufficiency. Neuropathological findings revealed severe loss of spinal cord motor neurons, and immunohistochemistry using an anti-misfolded SOD1 antibody revealed aggregates in the spinal cord. Genetic analyses revealed a c.357_357 + 2dup at the exon 4–intron 4 boundary of SOD1 in three patients. cDNA analysis of the proband suggested the presence of a valine (p.Val120dup) duplication in the heterozygous state, and the SOD1 transcript level showed no significant differences from those of healthy controls. In silico structural analyses predicted that p.Val120dup could affect the structure of the β-barrels and copper ion binding site of SOD1, suggesting an abnormal conformation of SOD1 that is predicted to interfere with the binding of copper ions. Conclusion: We identified a novel in-frame duplication variant in the C-terminus of β7 of SOD1. This genotype–structure–phenotype study of SOD1 provides valuable insights into disease-causing mechanisms. en-copyright= kn-copyright= en-aut-name=NakajimaMasanori en-aut-sei=Nakajima en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaruseHiroya en-aut-sei=Naruse en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RikuYuichi en-aut-sei=Riku en-aut-mei=Yuichi 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=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamuraYoshitsugu en-aut-sei=Nakamura en-aut-mei=Yoshitsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IshidaShimon en-aut-sei=Ishida en-aut-mei=Shimon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamadaTakashi en-aut-sei=Yamada en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MoroNaoki en-aut-sei=Moro en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KotsukiNaoki en-aut-sei=Kotsuki en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NagaiKentaro en-aut-sei=Nagai en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TokushigeShin-ichi en-aut-sei=Tokushige en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UchiboriAyumi en-aut-sei=Uchibori en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OishiChizuko en-aut-sei=Oishi en-aut-mei=Chizuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YabataHiroyuki en-aut-sei=Yabata en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=UrushitaniMakoto en-aut-sei=Urushitani en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IwasakiYasushi en-aut-sei=Iwasaki en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=19 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=20 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=21 ORCID= en-aut-name=IchikawaYaeko en-aut-sei=Ichikawa en-aut-mei=Yaeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Neurology, Kyorin University School of Medicine kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University 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, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Division of Neurology, Department of Internal Medicine IV, Osaka Medical and Pharmaceutical University kn-affil= affil-num=8 en-affil=Division of Neurology, Department of Internal Medicine IV, Osaka Medical and Pharmaceutical University kn-affil= affil-num=9 en-affil=Department of Pathology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=10 en-affil=Department of Neurology, Kyorin University School of Medicine kn-affil= affil-num=11 en-affil=Department of Neurology, Kyorin University School of Medicine kn-affil= affil-num=12 en-affil=Department of Neurology, Kyorin University School of Medicine kn-affil= affil-num=13 en-affil=Department of Neurology, Kyorin University School of Medicine kn-affil= affil-num=14 en-affil=Department of Neurology, Kyorin University School of Medicine kn-affil= affil-num=15 en-affil=Department of Neurology, Kyorin University School of Medicine kn-affil= affil-num=16 en-affil=Department of Neurology, Shiga University of Medical Science kn-affil= affil-num=17 en-affil=Department of Neurology, Shiga University of Medical Science kn-affil= affil-num=18 en-affil=Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University kn-affil= affil-num=19 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=21 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=22 en-affil=Department of Neurology, Kyorin University School of Medicine kn-affil= en-keyword=Familial amyotrophic lateral sclerosis kn-keyword=Familial amyotrophic lateral sclerosis en-keyword=SOD1 kn-keyword=SOD1 en-keyword=in-frame duplication kn-keyword=in-frame duplication en-keyword=protein structure kn-keyword=protein structure en-keyword=misfolded protein kn-keyword=misfolded protein 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=106 cd-vols= no-issue=12 article-no= start-page=002177 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251217 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Thorough characterization of a new curvulavirid from a Japanese strain of Cryphonectria nitschkei en-subtitle= kn-subtitle= en-abstract= kn-abstract=A new curvulavirid was isolated from a Japanese strain of the filamentous ascomycete Cryphonectria nitschkei and thoroughly characterized. The virus termed Cryphonectria nitschkei curvulavirus 1 (CnCvV1) has a bi-segmented dsRNA genome. CnCvV1 dsRNA1 encodes an RNA-dependent RNA polymerase (592 amino acids), while dsRNA2 possesses two ORFs, one that encodes a protein associated with the genomic dsRNA and the other that encodes a hypothetical protein of unknown function. CnCvV1 could be experimentally introduced into another virus-free strain of C. nitschkei and two strains of different fungal species within the genus Cryphonectria (Cryphonectria parasitica and Cryphonectria carpinicola). Based on phenotypic comparison, the virus caused asymptomatic infection in the three newly established fungal strains. However, there was a reduced colony growth rate and increased CnCvV1 accumulation in an RNA silencing-deficient mutant (Δdcl2), relative to the wt strain EP155 of a model virus host fungus (C. parasitica). These findings suggest that CnCvV1 is targeted by RNA silencing in C. parasitica. This study provides a foundation for further exploration of curvulavirids that have been biologically understudied. en-copyright= kn-copyright= en-aut-name=ShahiSabitree en-aut-sei=Shahi en-aut-mei=Sabitree kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisanoSakae en-aut-sei=Hisano en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Sa'diyahWasiatus en-aut-sei=Sa'diyah en-aut-mei=Wasiatus kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakakiYoshihiro en-aut-sei=Takaki en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=​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 for Extra-cutting-edge Science and Technology Avant-garde Research (X-star), Japan Agency for Marine-Earth Science and Technology (JAMSTEC) kn-affil= affil-num=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=curvulavirus kn-keyword=curvulavirus en-keyword=Cryphonectria carpinicola kn-keyword=Cryphonectria carpinicola en-keyword=Cryphonectria nitschkei kn-keyword=Cryphonectria nitschkei en-keyword=Cryphonectria parasitica kn-keyword=Cryphonectria parasitica en-keyword=fungal dsRNA virus kn-keyword=fungal dsRNA virus en-keyword=host range kn-keyword=host range en-keyword=RNA silencing kn-keyword=RNA silencing END start-ver=1.4 cd-journal=joma no-vol=37 cd-vols= no-issue=6 article-no= start-page=1392 end-page=1399 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Directed Poisoning Attacks on FRIT in Adaptive Cruise Control en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent advances in connected-vehicle technologies have enabled the large-scale collection of driving data, facilitating the deployment of data-driven control schemes. Although these methods offer advantages by eliminating the need for explicit modeling, they also introduce vulnerabilities due to their reliance on stored data. This study investigates a class of targeted data poisoning attacks on fictitious reference iterative tuning, a widely used data-driven controller tuning approach. We present a method that allows an adversary to influence closed-loop dynamics by manipulating the training data so that the resulting controller behavior matches a maliciously defined reference response. This strategy differs from conventional poisoning attacks, which aim only to the degrade control performance. Instead, it enables deliberate alteration of control characteristics such as overshoot and convergence time. The proposed attack is formulated as a constrained optimization problem under bounded tampering signals. Through a numerical study involving adaptive cruise control with stop functionality, we show that minor data modifications, indistinguishable from sensor noise, can cause significant degradation in control behavior. These findings highlight the need for robust security mechanisms in data-driven control implementation. en-copyright= kn-copyright= en-aut-name=IkezakiTaichi en-aut-sei=Ikezaki en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SawadaKenji en-aut-sei=Sawada en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanekoOsamu en-aut-sei=Kaneko en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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 Mechanical Engineering, The University of Osaka kn-affil= affil-num=3 en-affil=Graduate School of Informatics and Engineering, The University of Electro-Communications kn-affil= en-keyword=cyberattack kn-keyword=cyberattack en-keyword=data-driven control kn-keyword=data-driven control en-keyword=cruise control kn-keyword=cruise control en-keyword=FRIT kn-keyword=FRIT en-keyword=poisoning attack kn-keyword=poisoning attack 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=NakazatoKen’ichiro en-aut-sei=Nakazato en-aut-mei=Ken’ichiro 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=11 cd-vols= no-issue= article-no= start-page=100998 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Robustness of the RGB image-based estimation for rice above-ground biomass by utilizing the dataset collected across multiple locations en-subtitle= kn-subtitle= en-abstract= kn-abstract=Above-ground biomass (AGB) is a critical phenotype representing crop growth. Non-invasive evaluations of AGB, including deep-learning-based red-green-blue (RGB) image analyses, are often specific to the training data. The robustness of the estimation model across untrained conditions is essential to monitor crop productivity globally, but it has yet to be fully assessed. This study aims to assess the robustness of a convolutional neural network (CNN) model for rice AGB estimation across five locations in three countries, and to demonstrate the feasibility of robust model via a practical approach. From transplanting to heading, 1957 RGB images were captured vertically downward over the rice canopy, covering approximately 1 m2. First, a base model was established using data collected from a single location. Then, its robustness was assessed using test datasets taken from the other four locations. The CNN model showed a significant variation in estimation accuracy across the untrained four locations, indicating insufficient robustness of the base model. Subsequently, we quantitatively tested the impact of improving training data diversity on model robustness by adding data from each of the four locations to the base model's training data. Adding at most 48 data points from a location achieved practical accuracy for the added location, with R2Ad above 0.8. Interestingly, adding data from one location sometimes improved the accuracy for other untrained locations as well. These findings suggest that collecting diverse training data for RGB-based estimation, combined with evaluation of robustness paves the way for on-site and instant AGB monitoring of rice. en-copyright= kn-copyright= en-aut-name=NakajimaKota en-aut-sei=Nakajima en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaitoKazuki en-aut-sei=Saito en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsujimotoYasuhiro en-aut-sei=Tsujimoto en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakaiToshiyuki en-aut-sei=Takai en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MochizukiAtsushi en-aut-sei=Mochizuki en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamaguchiTomoaki en-aut-sei=Yamaguchi en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IbrahimAli en-aut-sei=Ibrahim en-aut-mei=Ali kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MairouaSalifou Goube en-aut-sei=Mairoua en-aut-mei=Salifou Goube kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AndrianaryBruce Haja en-aut-sei=Andrianary en-aut-mei=Bruce Haja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatsuraKeisuke en-aut-sei=Katsura en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TanakaYu en-aut-sei=Tanaka en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=2 en-affil=International Rice Research Institute (IRRI) kn-affil= affil-num=3 en-affil=Japan International Research Center for Agricultural Sciences kn-affil= affil-num=4 en-affil=Japan International Research Center for Agricultural Sciences kn-affil= affil-num=5 en-affil=CHIBA Prefectural Agriculture and Forestry Research Center kn-affil= affil-num=6 en-affil=Faculty of Applied Biological Sciences, Gifu University kn-affil= affil-num=7 en-affil= Africa Rice Center (AfricaRice), Regional Station for the Sahel kn-affil= affil-num=8 en-affil=Africa Rice Center (AfricaRice) kn-affil= affil-num=9 en-affil=Laboratoire des Radioisotopes, Université d′Antananarivo kn-affil= affil-num=10 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=11 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Robustness kn-keyword=Robustness en-keyword=RGB image kn-keyword=RGB image en-keyword=Rice, Above-ground biomass kn-keyword=Rice, Above-ground biomass en-keyword=Convolutional neural network kn-keyword=Convolutional neural network END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=6 article-no= start-page=457 end-page=461 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=Exacerbation of Proteinuria in a Patient with Behçet’s Disease and IgA Nephropathy Following Colchicine Discontinuation en-subtitle= kn-subtitle= en-abstract= kn-abstract=This case involves a 23-year-old male who was diagnosed with Behçet’s disease 5 years ago and managed with colchicine. Two months ago, he underwent renal biopsy due to abnormal urinalysis and kidney dysfunction, leading to a diagnosis of IgA nephropathy. He subsequently underwent tonsillectomy followed by glucocorticoid pulse therapy. However, after the tonsillectomy, discontinuing colchicine led to increased proteinuria, despite the glucocorticoid pulse therapy. Upon reintroducing colchicine, urinary protein excretion decreased, achieving incomplete remission. These findings suggest that colchicine may be effective in decreasing proteinuria in patients with Behçet’s disease complicated by IgA nephropathy. en-copyright= kn-copyright= en-aut-name=AsakawaTomohiko en-aut-sei=Asakawa en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatayamaYu en-aut-sei=Katayama en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakurabuYoshimasa en-aut-sei=Sakurabu en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatayamaKatsuyoshi en-aut-sei=Katayama en-aut-mei=Katsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OnishiYasuhiro en-aut-sei=Onishi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Matsuoka-UchiyamaNatsumi en-aut-sei=Matsuoka-Uchiyama en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiHidemi en-aut-sei=Takeuchi en-aut-mei=Hidemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaKeiko en-aut-sei=Tanaka en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=UmebayashiRyoko en-aut-sei=Umebayashi en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakemotoRika en-aut-sei=Takemoto en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Behçet’s disease kn-keyword=Behçet’s disease en-keyword=IgA nephropathy kn-keyword=IgA nephropathy en-keyword=colchicine kn-keyword=colchicine 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=445 end-page=449 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=Perioperative Team Management Was Beneficially Associated with Prolonged Postoperative Hospital Stays after Long Lower-Abdominal Surgeries en-subtitle= kn-subtitle= en-abstract= kn-abstract=Our hospital began a PERIO program (perioperative patient management by a multi-disciplinary team from multiple departments) in 2016 to improve patient outcomes. We retrospectively analyzed the clinical effects of the PERIO program regarding the postoperative hospital stay (PHS) in the patients aged ≥ 18 years who underwent long lower-abdominal surgery at our hospital during the period April 2019 to March 2023. We excluded the cases of patients whose general anesthesia use was < 8 h, those for whom another surgery was performed simultaneously at another site, and emergency surgeries. The outcome was prolonged PHS, defined as exceeding the scheduled number of days specified in the patient’s clinical pathway. Among the 480 patients, prolonged PHS was observed for 270 patients (56.3%). In a multivariate logistic regression using advanced age, sex, high-risk general state, surgery requiring colon resection, serious adverse events (SAEs), and PERIO use, the following were associated with prolonged PHS: advance age (odds ratio [OR] 4.91, 95% confidence interval [CI]: 2.68-8.99, p=0.01), surgery requiring colon resection (OR 4.91, 95%CI: 2.68-8.99, p<0.001), SAE (OR 18.7, 95%CI: 7.22-48.2, p<0.001), and PERIO (OR 0.25, 95%CI: 0.13-0.47, p<0.001). The use of the PERIO program was thus beneficially associated with PHS after long lower-abdominal surgery. 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= affil-num=1 en-affil=Department of Anesthesiology and Intensive Care Medicine, National Cancer Center Hospital kn-affil= en-keyword=hospital stay kn-keyword=hospital stay en-keyword=ERAS kn-keyword=ERAS en-keyword=surgery kn-keyword=surgery en-keyword=cancer kn-keyword=cancer en-keyword=perioperative management kn-keyword=perioperative management END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=6 article-no= start-page=431 end-page=436 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=Association of Weekend Admission and In-Hospital Mortality in Adult Patients with Acute Myeloid Leukemia in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=The effect of weekend admission on patient mortality has been investigated in several therapeutic areas, including acute myeloid leukemia (AML), but the investigations’ results are controversial. We evaluated the relationship between in-hospital mortality and weekend admission in adult patients with AML in Japan by conducting a retrospective observational study using administrative data from 144 acute care hospitals from which patients were discharged between April 2014 and March 2019. The primary endpoint was in-hospital mortality, compared between weekend and weekday admissions. Among the 1,340 eligible patients, 11% (150) were admitted during a weekend. The in-hospital mortality rates of the patients admitted during weekends and those admitted on a weekday were 28% (42/150) and 17% (204/1190), respectively. After an adjustment for covariates, weekend admission was associated with a significantly higher risk of in-hospital mortality than weekday admission (HR 1.70, 95%CI: 1.20-2.40; p=0.003). However, such an association was not observed in patients treated in a bio-clean room (HR 1.26, 95%CI: 0.65-2.42). Our results demonstrate that for patients with AML, weekend admission was independently associated with a higher risk of death during hospitalization. An appropriate system is necessary for these patients. en-copyright= kn-copyright= en-aut-name=InoueTakahiro en-aut-sei=Inoue en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuwabaraHiroyo en-aut-sei=Kuwabara en-aut-mei=Hiroyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoKoh en-aut-sei=Yamamoto en-aut-mei=Koh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Healthcare Management Research Center, Chiba University Hospital kn-affil= affil-num=2 en-affil=Healthcare Management Research Center, Chiba University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology, Yokohama City Minato Red Cross Hospital kn-affil= en-keyword=acute leukemia kn-keyword=acute leukemia en-keyword=weekend admission kn-keyword=weekend admission en-keyword=in-hospital mortality kn-keyword=in-hospital mortality en-keyword=bio-clean room kn-keyword=bio-clean room 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 start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=6 article-no= start-page=413 end-page=419 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=COVID-19 and the Risks of Migraine and Headache: A Mendelian Randomization Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Several observational studies suggested that migraine headache attacks were associated with coronavirus disease 2019 (COVID-19). We investigated genetic causal links between COVID-19 phenotypes and the development of headache and migraine, including migraine with aura (MA) and migraine without aura (MO). We conducted a two-sample Mendelian randomization (MR) analysis to estimate the genetic association in European populations. The inverse-variance weighted (IVW) method was used as the main approach in the MR analyses, together with weighted median and MR-Egger methods. We also performed a series of sensitivity tests to assess the robustness of the MR results. The MR results demonstrated that COVID-19 severity, hospitalization, and susceptibility had no causal effect on the risks of headache, migraine, MA, or MO. No horizontal pleiotropy was detected, and the results were robust as supported by the sensitivity analysis findings. Our analyses identified no casual effect of COVID-19 severity, hospitalization, or susceptibility on the risks of headache or migraine in European populations. en-copyright= kn-copyright= en-aut-name=JiangZhiyun en-aut-sei=Jiang en-aut-mei=Zhiyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=XiYing en-aut-sei=Xi en-aut-mei=Ying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University kn-affil= affil-num=2 en-affil=Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University kn-affil= en-keyword=headache kn-keyword=headache en-keyword=migraine kn-keyword=migraine en-keyword=Mendelian randomization kn-keyword=Mendelian randomization en-keyword=COVID-19 kn-keyword=COVID-19 END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=6 article-no= start-page=405 end-page=412 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=Real-World Outcomes of Anti-Vascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration in Patients Aged 85 or Older en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigated the treatment outcomes of patients aged ≥85 years with neovascular age-related macular degeneration (nAMD) who received anti-vascular endothelial growth factor (anti-VEGF) therapy using either treat-and-extend (TAE) or pro re nata (PRN) regimens for 1 year in real-world clinical practice. Eighty-five eyes from 85 patients were included. Among them, types 1, 2, and 3 macular neovascularization and polypoidal choroidal vasculopathy were present in 27.1%, 17.6%, 18.8%, and 36.5%, respectively. TAE and PRN regimens were used in 43.5% and 56.5% of patients, respectively. At baseline, the PRN group was older and had worse best-corrected visual acuity (BCVA), greater central retinal thickness, and more intraretinal fluid than the TAE group. In the TAE group, the mean number of injections was 7.6, BCVA improved significantly, and all retinal fluid rates decreased. In the PRN group, the mean number of injections was 3.9, BCVA remained unchanged, and the rates of macular fibrosis and atrophy increased. No serious adverse events were observed in either group. Anti-VEGF therapy was safe for patients aged ≥ 85 years with nAMD, and the TAE regimen effectively improved BCVA in this population. BCVA remained unchanged in the PRN-treated patients, with baseline disease severity and/or undertreatment potentially influencing the outcomes. en-copyright= kn-copyright= en-aut-name=OuchiChihiro en-aut-sei=Ouchi en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Morizane HosokawaMio en-aut-sei=Morizane Hosokawa en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraShuhei en-aut-sei=Kimura en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShiodeYusuke en-aut-sei=Shiode en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoritaTetsuro en-aut-sei=Morita en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=anti-vascular endothelial growth factor therapy kn-keyword=anti-vascular endothelial growth factor therapy en-keyword=neovascular age-related macular degeneration kn-keyword=neovascular age-related macular degeneration en-keyword=age kn-keyword=age en-keyword=treat-and-extend kn-keyword=treat-and-extend en-keyword=pro re nata kn-keyword=pro re nata END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=4 article-no= start-page=104195 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Factors affecting the development of hypokalemia during apheresis in healthy donors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Despite being generally safe, apheresis for peripheral blood stem cell collection potentially disrupts electrolyte balance owing to the use of citric acid as an anticoagulant. As prior research has primarily studied hypocalcemia, information on the kinetics of potassium levels during apheresis in healthy donors is scarce. We investigated the fluctuation in potassium levels during apheresis and the risk factors for hypokalemia. This subanalysis used data from an open-label, randomized controlled trial of “oral calcium supplementation versus placebo in mitigating citrate toxicity” conducted between January 2021 and July 2022, at Okayama University Hospital. Potassium levels were significantly reduced after 5-day granulocyte colony-stimulating factor (G-CSF) administration (p < 0.0001), with seven patients (16.7 %) given oral potassium administration before apheresis because the treating physician deemed potassium levels potentially unsafe and three (7.1 %) presenting with hypokalemia at apheresis. Potassium levels after apheresis were significantly lower than those before apheresis (baseline; p < 0.0001), and 28 of 42 donors (66.7 %) experienced biochemical, clinically unapparent hypokalemia immediately after the completion of apheresis. A > 15 % reduction in potassium levels from baseline was associated with age and the acid citrate dextrose solution A (ACD-A) volume in univariate analysis. In the multivariable analysis, both factors were associated (hazard ratio [HR], 11.60; 95 % confidence interval [CI], 1.60–83.70; p = 0.02 and HR, 17.50; 95 % CI, 1.07–136.00; p = 0.04). In conclusion, G-CSF administration and apheresis ultimately induced hypokalemia in two-thirds of the donors. Older age and higher ACD-A volume may affect potassium levels during apheresis in healthy donors. en-copyright= kn-copyright= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbeMasaya en-aut-sei=Abe en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukumiTakuya en-aut-sei=Fukumi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Division of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=Allogeneic kn-keyword=Allogeneic en-keyword=Peripheral blood stem cells kn-keyword=Peripheral blood stem cells en-keyword=Hypokalemia kn-keyword=Hypokalemia en-keyword=Acid citrate dextrose solution A kn-keyword=Acid citrate dextrose solution A en-keyword=Healthy donors kn-keyword=Healthy donors END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=8 article-no= start-page=1537 end-page=1544 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250528 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phase-Ib dose-finding and pharmacokinetic trial of metformin combined with nivolumab for refractory/recurrent solid tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Our previous findings showed that the addition of metformin to nivolumab resulted in remarkable tumor regression and increased the number of tumor-infiltrating T cells in mouse models. Therefore, we conducted a phase Ib study using combination therapy with nivolumab and metformin in patients with refractory/recurrent solid tumors.
Methods This study consisted of two parts: 1, evaluating the maximum tolerated dose (MTD), safety, pharmacokinetics in solid tumors, and 2, principally investigating the safety at the recommended dose limited to thoracic and pancreatic cancers. Metformin and nivolumab were administered orally at doses of 750–2,250 mg/day and biweekly at a fixed intravenous dose of 3 mg/kg, respectively. Dose-limiting toxicity was evaluated within the first 4 weeks. Both metformin and nivolumab were continued until disease progression or discontinued because of toxicity.
Results In total, 17 and 24 patients were enrolled in parts 1 and 2, respectively. One patient experienced increased pancreatic enzyme levels (grade 4) and lactic acidosis (grade 3). No Grade 5 adverse events were observed. MTD was not reached up to 2,250 mg/day of metformin, 2,250 mg/day was selected for part 2. An objective response was observed in 4 of 41 patients. One-year progression-free and overall survival rates were 9.8% and 56.8%, respectively. Two patients remained alive without disease progression for more than three years.
Conclusions Nivolumab and metformin combination therapy was well-tolerated and showed preliminary signals of efficacy in a subset of patients. Further verification of the underlying mechanism in cases where treatment is effective is required.
Trial registration numbers UMIN registration number 000028405 https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000031915. en-copyright= kn-copyright= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio 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=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KozukiToshiyuki en-aut-sei=Kozuki en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AsagiAkinori en-aut-sei=Asagi en-aut-mei=Akinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaMichihiro en-aut-sei=Yoshida en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=9 ORCID= affil-num=1 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Gastrointestinal Medical Oncology, NHO Shikoku Cancer Center kn-affil= affil-num=6 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=Pancreatic cancer kn-keyword=Pancreatic cancer en-keyword=Thoracic tumors kn-keyword=Thoracic tumors en-keyword=Phase Ib kn-keyword=Phase Ib en-keyword=Anti-PD-1 antibody kn-keyword=Anti-PD-1 antibody en-keyword=Nivolumab kn-keyword=Nivolumab en-keyword=Metformin kn-keyword=Metformin END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=6 article-no= start-page=dsaf030 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251022 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=MedakaBase as a unified genomic resource platform for medaka fish biology en-subtitle= kn-subtitle= en-abstract= kn-abstract=Medaka, a group of small, mostly freshwater fishes in the teleost order Beloniformes, includes the rice fish Oryzias latipes, a useful model organism studied in diverse biological fields. Chromosome-scale genome sequences of the Hd-rR strain of this species were obtained in 2007, and its improved version has facilitated various genome-wide studies. However, despite its widespread utility, omics data for O. latipes are dispersed across various public databases and lack a unified platform. To address this, the medaka section of the National Bioresource Project (NBRP) of Japan established a genome informatics team in 2022 tasked with providing various in silico solutions for bench biologists. This initiative led to the launch of MedakaBase (https://medakabase.nbrp.jp), a web server that enables gene-oriented analysis including exhaustive sequence similarity searches. MedakaBase also provides on-demand browsing of diverse genome-wide datasets, including tissue-specific transcriptomes and intraspecific genomic variations, integrated with gene models from different sources. Additionally, the platform offers gene models optimized for single-cell transcriptome analysis, which often requires coverage of the 3′ untranslated region (UTR) of transcripts. Currently, MedakaBase provides genome-wide data for seven Oryzias species, including original data for O. mekongensis and O. luzonensis produced by the NBRP team. This article outlines technical details behind the data provided by MedakaBase. en-copyright= kn-copyright= en-aut-name=MorikamiKenji en-aut-sei=Morikami en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanizawaYasuhiro en-aut-sei=Tanizawa en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YaguraMasaru en-aut-sei=Yagura en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoMika en-aut-sei=Sakamoto en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawamotoShoko en-aut-sei=Kawamoto en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraYasukazu en-aut-sei=Nakamura en-aut-mei=Yasukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamaguchiKatsushi en-aut-sei=Yamaguchi en-aut-mei=Katsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShigenobuShuji en-aut-sei=Shigenobu en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=11 ORCID= affil-num=1 en-affil=Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems kn-affil= affil-num=2 en-affil=Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems kn-affil= affil-num=3 en-affil=Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems kn-affil= affil-num=4 en-affil=Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems kn-affil= affil-num=5 en-affil=Department of Genetics, Sokendai (Graduate University for Advanced Studies) kn-affil= affil-num=6 en-affil=Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems kn-affil= affil-num=7 en-affil=Trans-Omics Facility, National Institute for Basic Biology kn-affil= affil-num=8 en-affil=Trans-Omics Facility, National Institute for Basic Biology kn-affil= affil-num=9 en-affil=Laboratory of Bioresources, National Institute for Basic Biology, National Institutes of Natural Sciences kn-affil= affil-num=10 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=11 en-affil=Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems kn-affil= en-keyword=medaka kn-keyword=medaka en-keyword=comparative genomics kn-keyword=comparative genomics en-keyword=genome browser kn-keyword=genome browser en-keyword=MedakaBase kn-keyword=MedakaBase en-keyword=Beloniformes kn-keyword=Beloniformes END start-ver=1.4 cd-journal=joma no-vol=55 cd-vols= no-issue=5 article-no= start-page=547 end-page=555 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250223 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Multicenter, open-label, randomized, controlled study to test the utility of electronic patient-reported outcome monitoring in patients with unresectable advanced cancers or metastatic/recurrent solid tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Electronic patient-reported outcome (ePRO) monitoring for patients undergoing cancer chemotherapy may provide qualified and early detection of adverse events or disease-related symptoms, leading to improved patient care. The aim of this study is to examine whether addition of ePRO monitoring to routine medical care contributes to improved overall survival and quality of life of cancer patients undergoing chemotherapy. Patients with unresectable advanced cancers or metastatic/recurrent solid tumors receiving systemic chemotherapy will be randomized to an ePRO monitoring group and a usual care group. The ePRO group will conduct weekly symptom monitoring using an electronic device after study enrollment until the end of the study. Monitoring results will be returned to medical personnel and used as information for patient care. The primary endpoints are overall survival and health related quality of life. The initial target sample size for the study was 1500 patients. However, due to delays in enrollment, the target was readjusted to 500 patients. Enrollment has been completed, and the study is now in the follow-up phase. en-copyright= kn-copyright= en-aut-name=TairaNaruto en-aut-sei=Taira en-aut-mei=Naruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KiyotaNaomi en-aut-sei=Kiyota en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikawaYuichiro en-aut-sei=Kikawa en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoKyoko en-aut-sei=Kato en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KubotaKaoru en-aut-sei=Kubota en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TateishiRyosuke en-aut-sei=Tateishi en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakataAkinobu en-aut-sei=Nakata en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaritaYukiya en-aut-sei=Narita en-aut-mei=Yukiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=IwataHiroji en-aut-sei=Iwata en-aut-mei=Hiroji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=ShimozumaKojiro en-aut-sei=Shimozuma en-aut-mei=Kojiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MuroKei en-aut-sei=Muro en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IwamotoTetsuya en-aut-sei=Iwamoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakumotoYuki en-aut-sei=Takumoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ShiroiwaTakeru en-aut-sei=Shiroiwa en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FukudaTakashi en-aut-sei=Fukuda en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YamaguchiTakuhiro en-aut-sei=Yamaguchi en-aut-mei=Takuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HagiwaraYasuhiro en-aut-sei=Hagiwara en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MinamiHironobu en-aut-sei=Minami en-aut-mei=Hironobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Breast and Thyroid Surgery, Kawasaki Medical School kn-affil= affil-num=2 en-affil=Department of Medical Oncology and Hematology, Cancer Center, Kobe University Hospital kn-affil= affil-num=3 en-affil=Department of Breast Surgery, Kansai Medical University kn-affil= affil-num=4 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Medical Oncology, National Hospital Organization Nagoya Medical Center kn-affil= affil-num=6 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Advanced Clinical Research and Development, Nagoya City University kn-affil= affil-num=13 en-affil=Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School kn-affil= affil-num=14 en-affil=Department of Biomed Sciences, College of Life Sciences, Ritsumeikan University kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health kn-affil= affil-num=17 en-affil=Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health kn-affil= affil-num=18 en-affil=Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health kn-affil= affil-num=19 en-affil=Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health kn-affil= affil-num=20 en-affil=Division of Biostatistics, Tohoku University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Biostatistics, Division of Health Sciences and Nursing, The University of Tokyo Graduate School of Medicine kn-affil= affil-num=22 en-affil=Division of Medical Oncology and Hematology, Department of Medicine, Kobe University Graduate School of Medicine kn-affil= en-keyword=electronic patient-reported outcomes monitoring kn-keyword=electronic patient-reported outcomes monitoring en-keyword=advanced cancers kn-keyword=advanced cancers en-keyword=systemic chemotherapy kn-keyword=systemic chemotherapy en-keyword=randomized controlled study kn-keyword=randomized controlled study en-keyword=quality of life kn-keyword=quality of life en-keyword=overall survival kn-keyword=overall survival END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=1 article-no= start-page=1387 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=Tumor marker–guided precision BNCT for CA19-9–positive cancers: a new paradigm in molecularly targeted chemoradiation therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Boron neutron capture therapy (BNCT) is a molecularly targeted chemoradiation modality that relies on boron delivery agents such as p-borophenylalanine (BPA), which require LAT1 (L-type amino acid transporter 1) for tumor uptake. However, the limited efficacy of BPA in LAT1-low tumors restricts its therapeutic scope. To address this limitation, we developed a tumor marker–guided BNCT strategy targeting cancers overexpressing the clinically validated glycan biomarker CA19-9.
Methods: We conducted transcriptomic analyses using The Cancer Genome Atlas (TCGA) datasets to identify LAT1-low cancers with high CA19-9 expression. These analyses revealed elevated expression of fucosyltransferase 3 (FUT3), which underlies CA19-9 biosynthesis, in pancreatic, biliary, and ovarian malignancies. Based on this, we synthesized a novel boron compound, fucose-BSH, designed to selectively accumulate in CA19-9–positive tumors. We evaluated its physicochemical properties, pharmacokinetics, biodistribution, and antitumor efficacy in cell lines and xenograft models, comparing its performance to that of BPA.
Results: Fucose-BSH demonstrated significantly greater boron uptake in CA19-9–positive cell lines (AsPC-1, Panc 04.03, HuCCT-1, HSKTC, OVISE) compared to CA19-9–negative PANC-1. In HuCCT-1 xenografts, boron accumulation reached 36.2 ppm with a tumor/normal tissue ratio of 2.1, outperforming BPA. Upon neutron irradiation, fucose-BSH–mediated BNCT achieved > 80% tumor growth inhibition. Notably, fucose-BSH retained therapeutic efficacy in LAT1-deficient models where BPA was ineffective, confirming LAT1-independent targeting.
Conclusions: This study establishes a novel precision BNCT approach by leveraging CA19-9 as a tumor-selective glycan marker for boron delivery. Fucose-BSH offers a promising platform for expanding BNCT to previously inaccessible LAT1-low malignancies, including pancreatic, biliary, and ovarian cancers. These findings provide a clinically actionable strategy for tumor marker–driven chemoradiation and lay the foundation for translational application in BNCT. This strategy has the potential to support companion diagnostic development and precision stratification in ongoing and future BNCT clinical trials.
Translational Relevance: Malignancies with elevated CA19-9 expression, such as pancreatic, biliary, and ovarian cancers, are associated with poor prognosis and limited response to current therapies. This study presents a tumor marker–guided strategy for boron neutron capture therapy (BNCT) by leveraging CA19-9 glycan biology to enable selective tumor targeting via fucose-BSH, a novel boron compound. Through transcriptomic data mining and preclinical validation, fucose-BSH demonstrated LAT1-independent boron delivery, potent BNCT-mediated cytotoxicity, and tumor-specific accumulation in CA19-9–positive models. These findings support a precision chemoradiation approach that addresses a critical gap in BNCT applicability, offering a clinically actionable pathway for patient stratification and therapeutic development in CA19-9–expressing cancers. en-copyright= kn-copyright= en-aut-name=KanehiraNoriyuki en-aut-sei=Kanehira en-aut-mei=Noriyuki 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=TajimaTomoyuki en-aut-sei=Tajima en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OsoneTatsunori en-aut-sei=Osone en-aut-mei=Tatsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=FujimotoTakuya en-aut-sei=Fujimoto en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakuraiYoshinori en-aut-sei=Sakurai en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KondoNatsuko en-aut-sei=Kondo en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagahisaNarikazu en-aut-sei=Nagahisa en-aut-mei=Narikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KameiKaoru en-aut-sei=Kamei en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujitaTaiga en-aut-sei=Fujita en-aut-mei=Taiga kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MoriharaAkira en-aut-sei=Morihara en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakaguchiYutaka en-aut-sei=Takaguchi en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= en-aut-name=TakaradaTakeshi en-aut-sei=Takarada en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 ORCID= en-aut-name=SuzukiMinoru en-aut-sei=Suzuki en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health 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=Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=8 en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=12 en-affil=Graduate School of Environmental, Life Science, Okayama University kn-affil= affil-num=13 en-affil=Faculty of Sustainable Design, Department of Material Design and Engineering, University of Toyama kn-affil= affil-num=14 en-affil=Department of Applied Chemistry, Kindai University kn-affil= affil-num=15 en-affil=Department of Regenerative Science, 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=Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= en-keyword=Boron neutron capture therapy (BNCT) kn-keyword=Boron neutron capture therapy (BNCT) en-keyword=Precision BNCT kn-keyword=Precision BNCT en-keyword=Fucose-conjugated medicine kn-keyword=Fucose-conjugated medicine en-keyword=CA19-9 kn-keyword=CA19-9 en-keyword=Drug discovery kn-keyword=Drug discovery END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=12 article-no= start-page=577 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of miR-128-3p on Renal Inflammation in a Rat Periodontitis Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: The study aim was to investigate the effects of extracellular vesicles (EVs) derived miR-128-3p on renal inflammation using a rat periodontitis model. Methods: Ten-week-old male Wistar rats were divided into two groups: a control (n = 8) and a lipopolysaccharides (LPS) group (n = 8). The LPS group received LPS (Porphyromonas gingivalis) injection in the gingiva for 7 days. At the end of the experiment, plasma, gingival tissue, and kidney samples were collected. Hematoxylin and eosin staining was performed to evaluate the glomerular tissue injury score. Bioinformatic analysis was conducted to identify potential target genes of miR-128-3p. The reverse transcription-quantitative polymerase chain reaction was performed to evaluate miR-128-3p, inflammatory, pro-inflammatory cytokine, chemokine and predicting gene’s expression. The control and LPS groups were compared using Welch’s t-test. p-values < 0.05 were considered to indicate statistical significance. Results: The kidney glomerular tissue injury score was significantly higher in the LPS than in the control group. miR-128-3p expression in the LPS group was significantly higher in the gingival tissue and plasma. mRNAs (interleukin [IL]-1β, tumor necrosis factor [TNF]-α, C-X3-C motif chemokine ligand 1 [CX3CL1], and C-X-C motif chemokine ligand 7 [CXCL7]) expression was higher in the kidney of the LPS group. The potential target genes of activin A receptor type I (Acvr1), ribosomal protein S6 kinase B1 (Rps6kb1), and transforming growth factor beta receptor type 1 (Tgfbr1) were significantly lower in the kidneys of the LPS group. Conclusions: EVs-derived miR-128-3p in LPS induced periodontitis may cause kidney inflammation which may be mediated by, Rps6kb1, Tgfbr1, and Acvr1. en-copyright= kn-copyright= en-aut-name=NurhamimMohammad en-aut-sei=Nurhamim en-aut-mei=Mohammad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ZhangYixuan en-aut-sei=Zhang en-aut-mei=Yixuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakaharaMomoko en-aut-sei=Nakahara en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukuharaDaiki en-aut-sei=Fukuhara en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagashimaYosei en-aut-sei=Nagashima en-aut-mei=Yosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaruyamaTakayuki en-aut-sei=Maruyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Health, Takarazuka University of Medical and Health Care kn-affil= affil-num=8 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=extracellular vesicles kn-keyword=extracellular vesicles en-keyword=miR-128-3p kn-keyword=miR-128-3p en-keyword=mRNA kn-keyword=mRNA en-keyword=inflammation kn-keyword=inflammation en-keyword=periodontitis kn-keyword=periodontitis en-keyword=renal inflammation kn-keyword=renal inflammation en-keyword=lipopolysaccharide kn-keyword=lipopolysaccharide END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=EUS-Guided Versus Percutaneous Transhepatic Drainage of Liver Abscesses: A Multicenter Endohepatology Study in Western Japan (EPIC-LA Study) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: Percutaneous transhepatic liver abscess drainage (PTAD) and endoscopic ultrasound-guided liver abscess drainage (EUS-LAD) have several limitations. Recently, because of technical improvements in echoendoscope maneuvers, EUS-guided access for the right hepatic lobe has been reported. The aim of this multicenter, retrospective study was to compare clinical outcomes of PTAD and EUS-LAD including the right hepatic lobe in West Japan.
Method: This retrospective, multicenter study included consecutive patients with liver abscesses between January 2019 and November 2024. The primary outcome in this study was the clinical success rate compared between EUS-LAD and PTAD.
Results: During the study period, 1012 consecutive patients developed liver abscesses. Of them, 734 patients were excluded, 43 underwent EUS-LAD and 235 patients underwent PTAD. After propensity score-matched analysis, the clinical success rate was significantly higher in the EUS-LAD group (97.7%, 42/43) than in the PTAD group (79.1%, 34/43) (p = 0.007). After a propensity score-matched analysis, 25 patients were included in each group. The clinical success rate was significantly higher in the EUS-LAD group (100%, 25/25) than in the PTAD group (84%, 21/25) (p = 0.037). Adverse events were also significantly higher in the PTAD group (16%, 5/25) than in the EUS-LAD group (p = 0.025). In addition, the median length of hospital stay was significantly shorter in the EUS-LAD group (15 days) than in the PTAD group (22 days) (p = 0.005).
Conclusions: EUS-LAD using a metal stent might be one of the options, but further randomized, controlled trials are needed. en-copyright= kn-copyright= en-aut-name=OguraTakeshi en-aut-sei=Ogura en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaTaira en-aut-sei=Kuroda en-aut-mei=Taira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuuraTakanori en-aut-sei=Matsuura en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitadaiJun en-aut-sei=Kitadai en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KitagawaKoh en-aut-sei=Kitagawa en-aut-mei=Koh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItonagaMasahiro en-aut-sei=Itonaga en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeshitaKotaro en-aut-sei=Takeshita en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsumoriTomoaki en-aut-sei=Matsumori en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=EmoriTomoya en-aut-sei=Emori en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakenakaMamoru en-aut-sei=Takenaka en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ImaiHajime en-aut-sei=Imai en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MandaiKoichiro en-aut-sei=Mandai en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShintaniShuhei en-aut-sei=Shintani en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujimoriNao en-aut-sei=Fujimori en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShiomiHideyuki en-aut-sei=Shiomi en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=AsadaMasanori en-aut-sei=Asada en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SagamiRyota en-aut-sei=Sagami en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MaruyamaHirotsugu en-aut-sei=Maruyama en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IkeuraTsukasa en-aut-sei=Ikeura en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ShimataniMasaaki en-aut-sei=Shimatani en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=NishikioriHidefumi en-aut-sei=Nishikiori en-aut-mei=Hidefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 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=22 ORCID= en-aut-name=KokubuMasahito en-aut-sei=Kokubu en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KamadaHideki en-aut-sei=Kamada en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=IshidaYusuke en-aut-sei=Ishida en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=HakodaAkitoshi en-aut-sei=Hakoda en-aut-mei=Akitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KitanoMasayuki en-aut-sei=Kitano en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= affil-num=1 en-affil=Pancreatobiliary Advanced Medical Center, Osaka Medical and Pharmaceutical University Hospital kn-affil= affil-num=2 en-affil=Gastroenterology Center, Ehime Prefectural Hospital kn-affil= affil-num=3 en-affil=Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Nara Medical University kn-affil= affil-num=6 en-affil=Second Department of Internal Medicine, Wakayama Medical University kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Tane General Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Gastroenterology, Wakayama Rosai Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine Graduate School of Medical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Okanami General Hospital kn-affil= affil-num=12 en-affil=Department of Gastroenterology, Kyoto Second Red Cross Hospital kn-affil= affil-num=13 en-affil=Department of Gastroenterology, Shiga University of Medical Science kn-affil= affil-num=14 en-affil=Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=15 en-affil=Division of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo Medical University kn-affil= affil-num=16 en-affil=Department of Gastroenterology and Hepatology, Japanese Red Cross Osaka Hospital kn-affil= affil-num=17 en-affil=Department of Gastroenterology, Faculty of Medicine, Oita University kn-affil= affil-num=18 en-affil=Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University kn-affil= affil-num=19 en-affil=Division of Gastroenterology and Hepatology, Kansai Medical University Hospital kn-affil= affil-num=20 en-affil=Department of Gastroenterology and Hepatology, Kansai Medical University Medical Center kn-affil= affil-num=21 en-affil=Department of Gastroenterology, Oita San-ai Medical Center kn-affil= affil-num=22 en-affil=Department of Endoscopy, Okayama University Hospital kn-affil= affil-num=23 en-affil=Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine kn-affil= affil-num=24 en-affil=Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University kn-affil= affil-num=25 en-affil=Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University kn-affil= affil-num=26 en-affil=2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University kn-affil= affil-num=27 en-affil=Second Department of Internal Medicine, Wakayama Medical University kn-affil= en-keyword=drainage kn-keyword=drainage en-keyword=endoscopic ultrasound-guided liver abscess drainage kn-keyword=endoscopic ultrasound-guided liver abscess drainage en-keyword=EUS kn-keyword=EUS en-keyword=liver abscess kn-keyword=liver abscess en-keyword=percutaneous transhepatic liver abscess drainage kn-keyword=percutaneous transhepatic liver abscess drainage END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=1 article-no= start-page=2586329 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251130 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Asiatic acid, a novel ciprofloxacin adjuvant inhibits Shigella flexneri infection en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bacterial infection caused by intracellular pathogens such as Shigella flexneri is a rapidly increasing global health concern that requires urgent and necessary action. The dearth of licensed vaccines against shigellosis and the decline in susceptibility to conventional antibiotics has encouraged the development of new antibiotic principles and drugs. The treatment options are decreasing faster than the discovery rate of new antibacterial agents. Combinatorial approach of antibiotics with non-antibiotic adjuvants is a promising aspect to treat resistant bacterial infections. Asiatic acid, a membrane-disrupting triterpenoid with wide antimicrobial and immunomodulatory properties, can potentiate antibiotics, but the exact mechanisms remain broadly unexplored. Therefore, in this study, we screened the interaction of asiatic acid with several antibiotics. The results showed synergistic interactions of asiatic acid with antibiotics against susceptible and multidrug-resistant S. flexneri clinical isolates. Particularly important was the interaction of asiatic acid with the quinolone antibiotics ciprofloxacin and nalidixic acid. A detailed study showed that combined treatment of asiatic acid with ciprofloxacin inhibited S. flexneri biofilm formation and resistance development. An increase in membrane disruption and depolarization upon co-treatment was evident by surface electron and confocal microscopy. In addition, asiatic acid and ciprofloxacin synergism was identified to inhibit efflux activity and intracellular bacterial viability. However, asiatic acid showed no synergistic toxicity with ciprofloxacin towards mammalian cells. The antibacterial activity was further verified in a S. flexneri infected mice model. Therapeutic benefits were evident with reduced bacterial burden, recovery from intestinal tissue damage and increase in mice survivability. The results showed that this combination can target the bacterial membrane, efflux pump proteins and biofilm formation, thereby preventing resistance development. The combination treatment offers a proof of concept in targeting essential bacterial activities and might be developed into a novel and efficient treatment alternative against S. flexneri. en-copyright= kn-copyright= en-aut-name=MaitraPriyanka en-aut-sei=Maitra en-aut-mei=Priyanka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BhuktaSamhati en-aut-sei=Bhukta en-aut-mei=Samhati kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=KayetPratanu en-aut-sei=Kayet en-aut-mei=Pratanu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BasakSurajit en-aut-sei=Basak en-aut-mei=Surajit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=KitaharaKei en-aut-sei=Kitahara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=DuttaShanta en-aut-sei=Dutta en-aut-mei=Shanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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 Clinical Medicine, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=4 en-affil=Division of Bioinformatics, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=5 en-affil=Division of Bioinformatics, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=6 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Collaborative Research Center of Okayama University for Infectious Diseases in India, ICMR-National Institute for Research in Bacterial Infections kn-affil= affil-num=8 en-affil=Department of Bacteriology, 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=Shigella flexneri kn-keyword=Shigella flexneri en-keyword=asiatic acid kn-keyword=asiatic acid en-keyword=ciprofloxacin kn-keyword=ciprofloxacin en-keyword=adjuvant kn-keyword=adjuvant en-keyword=membrane damage kn-keyword=membrane damage en-keyword=depolarization kn-keyword=depolarization en-keyword=nuclear damage kn-keyword=nuclear damage en-keyword=efflux inhibitor kn-keyword=efflux inhibitor END start-ver=1.4 cd-journal=joma no-vol=177 cd-vols= no-issue= article-no= start-page=113652 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-term effects of forest growth dynamics and climate change on groundwater recharge and evapotranspiration in a steep catchment of western Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Growing water demand for human and environmental needs has led to increased reliance on groundwater resources. However, groundwater is a finite resource, and its sustainability is closely linked to recharge processes, which are influenced by forest growth dynamics as well as climate change. Evapotranspiration, largely driven by vegetation cover and climatic conditions, represents a major component of terrestrial water loss that can reduce groundwater recharge. In this study, forest growth trends, reflecting the complete developmental stages from juvenile to post-maturity of a representative species, were reconstructed using remote sensing data, forest inventories, and field studies, and incorporated into the SWAT model to evaluate their impacts on groundwater recharge and evapotranspiration as indicators of forest hydrological function and ecosystem health. The model’s vegetation growth simulation was enhanced and uncertainty reduced by dynamically updating it with MODIS-derived leaf area index (LAI) at 5-year intervals. Groundwater recharge estimates were further improved through multi-variable calibration using Penman–Monteith–Leuning evapotranspiration (V2) and streamflow data to ensure water budget closure. Results showed that evergreen conifer growth from planting to maturity significantly reduced groundwater recharge (–4.7 mm/year) and increased evapotranspiration (+7.6 mm/year). In contrast, natural and mature deciduous broadleaf forests showed more stable recharge and evapotranspiration trends. Rising temperatures were identified as a key climatic driver of reduced recharge and increased evapotranspiration, reflecting broader global warming impacts. This study demonstrates that forest growth dynamics, especially during the critical transition from planting to maturity, alongside climate change, play a crucial role in shaping the catchment’s water balance and offer valuable insights for sustainable groundwater management, particularly in transitional forest ecosystems. en-copyright= kn-copyright= en-aut-name=GuyoRendilicha Halake en-aut-sei=Guyo en-aut-mei=Rendilicha Halake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangKunyang en-aut-sei=Wang en-aut-mei=Kunyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OnoderaShin-ichi en-aut-sei=Onodera en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaitoMitsuyo en-aut-sei=Saito en-aut-mei=Mitsuyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoroizumiToshitsugu en-aut-sei=Moroizumi en-aut-mei=Toshitsugu 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 Advanced Science and Engineering, Hiroshima University kn-affil= affil-num=3 en-affil=Graduate School of Advanced Science and Engineering, Hiroshima University kn-affil= affil-num=4 en-affil=Graduate School of Advanced Science and Engineering, Hiroshima University kn-affil= affil-num=5 en-affil= Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=Forest growth kn-keyword=Forest growth en-keyword=SWAT kn-keyword=SWAT en-keyword=Groundwater recharge kn-keyword=Groundwater recharge en-keyword=Evapotranspiration kn-keyword=Evapotranspiration en-keyword=MODIS LAI kn-keyword=MODIS LAI en-keyword=PML_V2 kn-keyword=PML_V2 en-keyword=Climate change kn-keyword=Climate change END start-ver=1.4 cd-journal=joma no-vol=191 cd-vols= no-issue= article-no= start-page=107592 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=A novel wearable dosimeter system that can analyze the incident direction of X-rays for medical dosimetry – Improvements to the detector arrangements and analysis algorithm – en-subtitle= kn-subtitle= en-abstract= kn-abstract=When performing real-time dosimetry using an active-type dosimeter during clinical fluoroscopic procedures, angular dependence of dosimeter response should be taken into account. Our research group addressed this issue and proposed a triple-type dosimeter that can determine the incident angle of scattered X-rays. The triple-type detector consists of three active dosimeters. The two side dosimeters have slope filters to enhance the angular dependence and are intentionally tilted. The central dosimeter faces forward. The incident angle of X-rays (θin) is estimated using the signal differences between the central dosimeter and the left and/or right dosimeters. Then, the absolute dose is determined by correcting the angular dependence of the central dosimeter based on the estimated θin. In order to verify the concept of the triple-type dosimeter, we conducted a proof-of-concept experiment using clinical X-ray fluoroscopic equipment. Scattered X-rays were generated by irradiating an elliptical cylindrical water phantom. The response of the triple-type dosimeter was evaluated by rotating it to vary the incident angle of scattered X-rays generated by the water phantom. The proposed dosimetry system could estimate the θin over an angular range of ±80° (with uncertainty of 1.35°), which is 30° wider than the previous version, and successfully determined the absolute doses after correction for the angular dependence of the dosimeter. Although the active-type dosimeter had a systematic uncertainty related to the angular dependence of ±15.2 %, our system succeeded in reducing the systematic uncertainty to ±3.2 %. en-copyright= kn-copyright= en-aut-name=AsaharaTakashi en-aut-sei=Asahara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishigamiRina en-aut-sei=Nishigami en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiDaiki en-aut-sei=Kobayashi en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KimotoNatsumi en-aut-sei=Kimoto en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GotoSota en-aut-sei=Goto en-aut-mei=Sota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakegamiKazuki en-aut-sei=Takegami en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshiiRin en-aut-sei=Ishii en-aut-mei=Rin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MitaniMana en-aut-sei=Mitani en-aut-mei=Mana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HondaMitsugi en-aut-sei=Honda en-aut-mei=Mitsugi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HayashiHiroaki en-aut-sei=Hayashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=3 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=4 en-affil=Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University kn-affil= affil-num=5 en-affil=Faculty of Health Science, Kobe Tokiwa University kn-affil= affil-num=6 en-affil=Department of Radiological Technology, Yamaguchi University Hospital kn-affil= affil-num=7 en-affil=College of Transdisciplinary Sciences for Innovation, Kanazawa University kn-affil= affil-num=8 en-affil=Division of Radiological Technology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=9 en-affil=Division of Radiological Technology, Medical Support Department, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=11 en-affil=College of Transdisciplinary Sciences for Innovation, Kanazawa University kn-affil= en-keyword=Wearable active-type dosimeter kn-keyword=Wearable active-type dosimeter en-keyword=X-ray incident direction kn-keyword=X-ray incident direction en-keyword=Occupational dose kn-keyword=Occupational dose en-keyword=Interventional radiology kn-keyword=Interventional radiology END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=10 article-no= start-page=908 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251016 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Comparative Study of Authoring Performances Between In-Situ Mobile and Desktop Tools for Outdoor Location-Based Augmented Reality en-subtitle= kn-subtitle= en-abstract= kn-abstract=In recent years, Location-Based Augmented Reality (LAR) systems have been increasingly implemented in various applications for tourism, navigation, education, and entertainment. Unfortunately, the LAR content creation using conventional desktop-based authoring tools has become a bottleneck, as it requires time-consuming and skilled work. Previously, we proposed an in-situ mobile authoring tool as an efficient solution to this problem by offering direct authoring interactions in real-world environments using a smartphone. Currently, the evaluation through the comparison between the proposal and conventional ones is not sufficient to show superiority, particularly in terms of interaction, authoring performance, and cognitive workload, where our tool uses 6DoF device movement for spatial input, while desktop ones rely on mouse-pointing. In this paper, we present a comparative study of authoring performances between the tools across three authoring phases: (1) Point of Interest (POI) location acquisition, (2) AR object creation, and (3) AR object registration. For the conventional tool, we adopt Unity and ARCore SDK. As a real-world application, we target the LAR content creation for pedestrian landmark annotation across campus environments at Okayama University, Japan, and Brawijaya University, Indonesia, and identify task-level bottlenecks in both tools. In our experiments, we asked 20 participants aged 22 to 35 with different LAR development experiences to complete equivalent authoring tasks in an outdoor campus environment, creating various LAR contents. We measured task completion time, phase-wise contribution, and cognitive workload using NASA-TLX. The results show that our tool made faster creations with 60% lower cognitive loads, where the desktop tool required higher mental efforts with manual data input and object verifications. en-copyright= kn-copyright= 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=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=Sandi KyawHtoo Htoo en-aut-sei=Sandi Kyaw en-aut-mei=Htoo Htoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=RiyantokoPrismahardi Aji en-aut-sei=Riyantoko en-aut-mei=Prismahardi Aji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Noprianto en-aut-sei=Noprianto en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=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=location-based augmented reality (LAR) kn-keyword=location-based augmented reality (LAR) en-keyword=in-situ authoring kn-keyword=in-situ authoring en-keyword=authoring workflow kn-keyword=authoring workflow en-keyword=cognitive workload kn-keyword=cognitive workload en-keyword=NASA-TLX kn-keyword=NASA-TLX END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue= article-no= start-page=101145 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=Characteristics of out-of-hospital cardiac arrest due to cerebrovascular disorders: a nationwide, retrospective, observational study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Data on out-of-hospital cardiac arrest (OHCA) due to cerebrovascular disorders is limited. This study aimed to describe the characteristics, outcomes, and annual trends of outcomes for OHCA originating from cerebrovascular disorders.
Methods: This study was a retrospective analysis using an Utstein-style Japanese National Registry. Adult patients with OHCA due to cerebrovascular disorders and transported to the hospital between 2005 and 2021 were included. The primary outcome was a favorable neurological outcome at 30-day. We analyzed factors associated with outcomes using a multivariable logistic regression model, then evaluated annual trends of outcomes for cerebrovascular-induced OHCA.
Results: Among 2,081,023 OHCA patients, 52,969 had cerebrovascular-induced cardiac arrest. Of these, 1903 (3.5 %) achieved a favorable neurological outcome. In the multivariable logistic regression model, male sex (adjusted odds ratio [aOR] 1.41, 95 % confidence interval [CI] 1.20–1.61), initial shockable rhythm (aOR 3.10, 95 % CI 2.18–4.40), witnessed cardiac arrest (aOR 1.92, 95 % CI: 1.57–2.34), and prehospital return of spontaneous circulation (ROSC) (aOR 11.1, 95 % CI: 9.09–13.5) were associated with favorable neurological outcomes. Prehospital adrenaline administration was negatively associated with favorable neurological outcomes (aOR 0.22, 95 % CI: 0.16–0.30). The proportion of patients with favorable neurological outcomes increased over time, rising from 3.14 % in 2005 to 4.12 % in 2021.
Conclusions: Although OHCA due to cerebrovascular disorders is generally associated with poor neurological outcomes, 3.5 % of the patients with cerebrovascular-induced OHCA in this study had favorable neurological outcomes, with a yearly trend improving over decades. Patient characteristics associated with a higher likelihood of a favorable neurological outcome included prehospital ROSC, initial shockable rhythm, and witnessed cardiac arrest. en-copyright= kn-copyright= en-aut-name=UedaYoshiyuki en-aut-sei=Ueda en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HongoTakashi en-aut-sei=Hongo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine kn-affil= affil-num=2 en-affil=Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine kn-affil= affil-num=3 en-affil=Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine kn-affil= affil-num=4 en-affil=Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine kn-affil= affil-num=5 en-affil=Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine kn-affil= affil-num=6 en-affil=Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine kn-affil= affil-num=7 en-affil=Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Epidemiology kn-affil= affil-num=8 en-affil=Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine kn-affil= affil-num=9 en-affil=Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine kn-affil= en-keyword=Cardiac arrest kn-keyword=Cardiac arrest en-keyword=Cardiopulmonary resuscitation kn-keyword=Cardiopulmonary resuscitation en-keyword=Cerebral hemorrhage kn-keyword=Cerebral hemorrhage en-keyword=Stroke kn-keyword=Stroke en-keyword=Subarachnoid hemorrhage kn-keyword=Subarachnoid hemorrhage END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e21664 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251014 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Biologically-Architected Wear and Damage-Resistant Nanoparticle Coating From the Radular Teeth of Cryptochiton stelleri en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nature utilizes simple building blocks to construct mechanically robust materials that demonstrate superior performance under extreme conditions. These exquisite structures result from the controlled synthesis and hierarchical assembly of nanoscale organic and mineral components that have provided critical evolutionary advantages to ensure survival. One such example is the ultrahard radular teeth found in mollusks, which are used to scrape against rock to feed on algae. Here, it is reported that the leading edges of these teeth consist of a wear-resistant coating that is comprised of densely packed ≈65 nm magnetic nanoparticles integrated within an organic matrix of chitin and protein. These mesocrystalline magnetite-based structures are assembled from smaller, highly aligned nanocrystals with inter/intracrystalline organics introduced during the crystallization process. Nanomechanical testing reveals that this multi-scale, nano-architected coating has a combination of increased hardness and a slight decrease in modulus versus geologic magnetite provides the surface of the chiton tooth with superior abrasion resistance. The mesocrystalline structures fracture at primary domain interfaces, corroborated by computational models, providing significant toughening to the tooth under extreme contact stresses. The design features revealed provide insight for the design and fabrication of next-generation advanced wear- and impact-resistant coatings for tooling, machinery, wind turbines, armor, etc. en-copyright= kn-copyright= en-aut-name=WangTaifeng en-aut-sei=Wang en-aut-mei=Taifeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChenYu en-aut-sei=Chen en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SarmientoEzra en-aut-sei=Sarmiento en-aut-mei=Ezra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HaoTaige en-aut-sei=Hao en-aut-mei=Taige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ArakakiAtsushi en-aut-sei=Arakaki en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NemotoMichiko en-aut-sei=Nemoto en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZavattieriPablo en-aut-sei=Zavattieri en-aut-mei=Pablo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KisailusDavid en-aut-sei=Kisailus en-aut-mei=David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Materials Science and Engineering, University of California kn-affil= affil-num=2 en-affil=Lyles School of Civil and Construction Engineering, Purdue University kn-affil= affil-num=3 en-affil=Department of Materials Science and Engineering, University of California kn-affil= affil-num=4 en-affil=Materials and Manufacturing Technologies Program, University of California kn-affil= affil-num=5 en-affil=Division of Biotechnology and Life Science, Institute of Engineering, Tokyo University of Agriculture and Technology kn-affil= affil-num=6 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=7 en-affil=Lyles School of Civil and Construction Engineering, Purdue University kn-affil= affil-num=8 en-affil=Department of Materials Science and Engineering, University of California kn-affil= en-keyword=biomineralization kn-keyword=biomineralization en-keyword=coatings kn-keyword=coatings en-keyword=damage tolerance kn-keyword=damage tolerance en-keyword=magnetite kn-keyword=magnetite en-keyword=mesocrystals kn-keyword=mesocrystals END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=8 article-no= start-page=e0328792 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250814 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Risk stratification for the prediction of skeletal-related events in patients with castration-resistant prostate cancer with bone metastases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Skeletal-related events (SREs) are common in patients with bone metastases from castration-resistant prostate cancer (CRPC). Despite advances in prostate cancer treatment, clinically validated predictive models for SREs in CRPC patients with bone metastases remain elusive. This gap in prognostic tools hinders optimal patient management and treatment planning for this high-risk population. This study aimed to develop a prediction model for SRE by investigating potential risk factors and classifying them into different groups. This model can be used to identify patients at high risk of SREs who need close follow-up. Between 2004 and 2013, 68 male patients with bone metastases from CRPC who were treated at our institute were evaluated for survival without SREs and survival without SREs of the spinal cord. The study analyzed clinical data at enrollment to identify risk factors for initial and spinal SREs. Multivariate analysis revealed that a high count of metastatic vertebrae, along with visceral or lymph node metastases, were significant risk factors. Patients were categorized into four subgroups based on the number of vertebral metastases and presence of visceral or lymph node metastases: 1) extensive vertebral and both types of metastases, 2) extensive vertebral without additional metastases, 3) some vertebral with other metastases, 4) some vertebral without additional metastases. The first SRE and spinal SRE occurred significantly sooner in the first subgroup compared to others. Incidence rates at 12 months for the first SRE were 56%, 40%, 27%, and 5%, and for the first spinal SRE were 47%, 40%, 27%, and 0% respectively. Patients with extensive vertebral and additional metastases require vigilant monitoring to mitigate SREs. en-copyright= kn-copyright= en-aut-name=HamadaMasanori en-aut-sei=Hamada en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakaharaRyuichi en-aut-sei=Nakahara en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SugiharaShinsuke en-aut-sei=Sugihara en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatayamaHaruyoshi en-aut-sei=Katayama en-aut-mei=Haruyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItanoTakuto en-aut-sei=Itano en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=InoueTomohiro en-aut-sei=Inoue en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakihiraShota en-aut-sei=Takihira en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AkezakiYoshiteru en-aut-sei=Akezaki en-aut-mei=Yoshiteru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= affil-num=3 en-affil= kn-affil= affil-num=4 en-affil= kn-affil= affil-num=5 en-affil= kn-affil= affil-num=6 en-affil= kn-affil= affil-num=7 en-affil= kn-affil= affil-num=8 en-affil= kn-affil= affil-num=9 en-affil= kn-affil= affil-num=10 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e00463-25 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251128 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Analysis of the drug target of the anti-tuberculosis compound OCT313: phosphotransacetylase is a potential drug target for anti-mycobacterial agents en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tuberculosis (TB) is one of the most common infectious diseases caused by bacteria worldwide. The increasing prevalence of multidrug-resistant TB (MDR-TB) and latent TB infection (LTBI) has intensified the global TB burden. Therefore, the development of new drugs for MDR-TB and LTBI is urgently required. We have reported that the derivative of dithiocarbamate sugar derivative, 2-acetamido-2-deoxy-β-D-glucopyranosyl N,N-dimethyldithiocarbamate (OCT313), exhibits anti-mycobacterial activity against MDR-MTB. Here, we identified the target of OCT313. In experimentally generated OCT313-resistant bacteria, adenine at position 1,092 in the metabolic enzyme phosphotransacetylase (PTA) gene was replaced with cytosine. This mutation is a nonsynonymous mutation that converts methionine to leucine at position 365 in the PTA protein. OCT313 inhibited the enzymatic activity of recombinant wild-type PTA, but not of the mutant PTA (M365L). PTA is an enzyme that produces acetyl-coenzyme A (acetyl-CoA) from acetyl phosphate and CoA and is involved in metabolic pathways; therefore, it was expected to also be active against dormant Mycobacterium tuberculosis bacilli. OCT313 exhibits antibacterial activity in the Wayne model of dormancy using Mycobacterium bovis BCG, and overexpression of PTA in OCT313-resistant bacilli restored sensitivity to OCT313. Collectively, the target of OCT313 is PTA, and OCT313 is a promising antimicrobial candidate for MDR-TB and LTBI. en-copyright= kn-copyright= en-aut-name=TakiiTakemasa en-aut-sei=Takii en-aut-mei=Takemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HasegawaTomohiro en-aut-sei=Hasegawa en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItohSaotomo en-aut-sei=Itoh en-aut-mei=Saotomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaedaShinji en-aut-sei=Maeda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WadaTakayuki en-aut-sei=Wada en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoritaYasuhiro en-aut-sei=Horita en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishiyamaAkihito en-aut-sei=Nishiyama en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsumotoSohkichi en-aut-sei=Matsumoto en-aut-mei=Sohkichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OharaNaoya en-aut-sei=Ohara en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KimishimaAoi en-aut-sei=Kimishima en-aut-mei=Aoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsamiYukihiro en-aut-sei=Asami en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HidaShigeaki en-aut-sei=Hida en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OnozakiKikuo en-aut-sei=Onozaki en-aut-mei=Kikuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=2 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=3 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=4 en-affil=Graduate School of Pharmaceutical Sciences, Hokkaido University of Sciences kn-affil= affil-num=5 en-affil=Department of Microbiology, Graduate School of Human Life and Ecology, Osaka Metropolitan University kn-affil= affil-num=6 en-affil=Department of Clinical Pharmaceutics, Graduate School of Medical Sciences, Nagoya City University kn-affil= affil-num=7 en-affil=Department of Bacteriology, Niigata University School of Medicine kn-affil= affil-num=8 en-affil=Department of Bacteriology, Niigata University School of Medicine kn-affil= affil-num=9 en-affil=Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Laboratory of Applied Microbial Chemistry, Ōmura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=11 en-affil=Laboratory of Applied Microbial Chemistry, Ōmura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=12 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=13 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= en-keyword=phosphotransacetylase kn-keyword=phosphotransacetylase en-keyword=acetyl coenzyme A kn-keyword=acetyl coenzyme A en-keyword=dithiocarbamate kn-keyword=dithiocarbamate en-keyword=N-acetyl glucosamine kn-keyword=N-acetyl glucosamine en-keyword=anti-mycobacterial agents kn-keyword=anti-mycobacterial agents en-keyword=latent tuberculosis infection kn-keyword=latent tuberculosis infection END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=19 article-no= start-page=9630 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251002 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Critical Requirement of Senescence-Associated CCN3 Expression in CD44-Positive Stem Cells for Osteoarthritis Progression en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage breakdown, synovial inflammation, and subchondral bone remodeling. Previous studies have shown that cellular communication network factor 3 (CCN3) expression increases with age in cartilage, and its overexpression promotes OA-like changes by inducing senescence-associated secretory phenotypes. This study aimed to investigate the effect of Ccn3 knockout (KO) on OA development using a murine OA model. Destabilization of the medial meniscus (DMM) surgery was performed in wild-type (WT) and Ccn3-KO mice. Histological scoring and staining were used to assess cartilage degeneration and proteoglycan loss. Gene and protein expressions of catabolic enzyme (Mmp9), hypertrophic chondrocyte marker (Col10a1), senescence marker, and cyclin-dependent kinase inhibitor 1A (Cdkn1a) were evaluated. Single-cell RNA sequencing (scRNA-seq) data from WT and Sox9-deficient cartilage were reanalyzed to identify Ccn3+ progenitor populations. Immunofluorescence staining assessed CD44 and Ki67 expression in articular cartilage. The effects of Ccn3 knockdown on IL-1β-induced Mmp13 and Adamts5 expression in chondrocytes were examined in vitro. Ccn3 KO mice exhibited reduced cartilage degradation and catabolic gene expression compared with WT mice post-DMM. scRNA-seq revealed enriched Ccn3-Cd44 double-positive cells in osteoblast progenitor, synovial mesenchymal stem cell, and mesenchymal stem cell clusters. Immunofluorescence showed increased CCN3+/CD44+ cells in femoral and tibial cartilage and meniscus. Ki67+ cells were significantly increased in DMM-treated Ccn3 KO cartilage, mostly CD44+. In vitro Ccn3 knockdown attenuated IL-1β-induced Mmp13 and Adamts5 expressions in chondrocytes. Ccn3 contributes to OA pathogenesis by promoting matrix degradation, inducing hypertrophic changes, and restricting progenitor cell proliferation, highlighting Ccn3 as a potential therapeutic target for OA. en-copyright= kn-copyright= en-aut-name=HabumugishaJanvier en-aut-sei=Habumugisha en-aut-mei=Janvier kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkudaRyuichiro en-aut-sei=Okuda en-aut-mei=Ryuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiroseKazuki en-aut-sei=Hirose en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuwaharaMiho en-aut-sei=Kuwahara en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WangZiyi en-aut-sei=Wang en-aut-mei=Ziyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OnoMitsuaki en-aut-sei=Ono en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KubotaSatoshi en-aut-sei=Kubota en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HattoriTakako en-aut-sei=Hattori en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=articular kn-keyword=articular en-keyword=cartilage kn-keyword=cartilage en-keyword=mesenchymal stem cells kn-keyword=mesenchymal stem cells en-keyword=nephroblastoma overexpressed protein kn-keyword=nephroblastoma overexpressed protein en-keyword=osteoarthritis kn-keyword=osteoarthritis END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=リモートセンシングとハイブリッドモデルを用いた森林炭素蓄積量の空間分布分析―ベトナム中部沿岸地域を対象として― kn-title=Spatiotemporal Evolution of Forest Carbon Storage under the Impact of Land Use/Land Cover Dynamics Using Multi-Source Remotely Sensed Data and Hybrid Models in the Central Coastal Region of Vietnam en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HO VIET HOANG en-aut-sei=HO VIET HOANG en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil=岡山大学大学院環境生命科学研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=WebスクレイピングとBERTモデルを用いた参考文献収集システムの研究 kn-title=A Study of Reference Paper Collection System Using Web Scraping and BERT Model en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=INZALI NAING en-aut-sei=INZALI NAING en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama university kn-affil=岡山大学大学院自然科学研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=垂直的骨格パターンの異なる成人における軟口蓋および気道内腔寸法に基づく上気道容積の臨床的予測モデル kn-title=Clinical Prediction Models for Upper Airway Volume Based on Soft Palate and Airway Lumen Dimensions in Adults With Varying Vertical Skeletal Patterns en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HABUMUGISHA JANVIER en-aut-sei=HABUMUGISHA JANVIER en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=活動性食欲不振モデルマウスにおける前頭前野および海馬におけるペリニューロナルネットおよびパルブアルブミン介在ニューロンの変化、および血中コルチコステロンとの相関性 kn-title=Alteration of perineuronal nets and parvalbumin interneurons in prefrontal cortex and hippocampus, and correlation with blood corticosterone in activity-based anorexia model mice en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NGUYEN DUY HOANG en-aut-sei=NGUYEN DUY HOANG en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=豚実験モデルを使ったフォンタン循環における機械的肺循環サポート kn-title=Mechanical Subpulmonary Support in Fontan Circulation: A Juvenile Porcine Experimental Model en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SAKODANaoya en-aut-sei=SAKODA en-aut-mei=Naoya kn-aut-name=迫田直也 kn-aut-sei=迫田 kn-aut-mei=直也 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=血管新生を誘導した皮下組織への膵島移植による生着率および機能の改善：マウスモデルによる検討 kn-title=Grafting Islets to a Prevascularized Subcutaneous Site to Improve Transplant Survival and Function: A Mouse Model en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OKADATsuyoshi en-aut-sei=OKADA en-aut-mei=Tsuyoshi kn-aut-name=岡田剛 kn-aut-sei=岡田 kn-aut-mei=剛 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=虚血性脳卒中モデルラットにおけるヒト改変骨髄由来間質細胞（SB623）の脳内移植と随意運動および強制運動の治療効果 kn-title=Therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) with voluntary and forced exercise in a rat model of ischemic stroke en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NAGASETakayuki en-aut-sei=NAGASE en-aut-mei=Takayuki kn-aut-name=永瀬喬之 kn-aut-sei=永瀬 kn-aut-mei=喬之 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=慢性外傷性脳症の再現性および定量的モデル：反復性の非出血性および非挫傷性の軽度外傷性脳損傷ラットは、ミクログリアの活性化、アストログリア症、およびタウオパチーを伴い行動障害を引き起こす kn-title=Repeated non-hemorrhagic and non-contusional mild traumatic brain injury in rats elicits behavioral impairment with microglial activation, astrogliosis, and tauopathy: Reproducible and quantitative model of chronic traumatic encephalopathy en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SUGAHARAChiaki en-aut-sei=SUGAHARA en-aut-mei=Chiaki kn-aut-name=菅原千明 kn-aut-sei=菅原 kn-aut-mei=千明 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=19 article-no= start-page=3144 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250927 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Utility of Same-Modality, Cross-Domain Transfer Learning for Malignant Bone Tumor Detection on Radiographs: A Multi-Faceted Performance Comparison with a Scratch-Trained Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Developing high-performance artificial intelligence (AI) models for rare diseases like malignant bone tumors is limited by scarce annotated data. This study evaluates same-modality cross-domain transfer learning by comparing an AI model pretrained on chest radiographs with a model trained from scratch for detecting malignant bone tumors on knee radiographs. Methods: Two YOLOv5-based detectors differed only in initialization (transfer vs. scratch). Both were trained/validated on institutional data and tested on an independent external set of 743 radiographs (268 malignant, 475 normal). The primary outcome was AUC; prespecified operating points were high-sensitivity (≥0.90), high-specificity (≥0.90), and Youden-optimal. Secondary analyses included PR/F1, calibration (Brier, slope), and decision curve analysis (DCA). Results: AUC was similar (YOLO-TL 0.954 [95% CI 0.937–0.970] vs. YOLO-SC 0.961 [0.948–0.973]; DeLong p = 0.53). At the high-sensitivity point (both sensitivity = 0.903), YOLO-TL achieved higher specificity (0.903 vs. 0.867; McNemar p = 0.037) and PPV (0.840 vs. 0.793; bootstrap p = 0.030), reducing ~17 false positives among 475 negatives. At the high-specificity point (~0.902–0.903 for both), YOLO-TL showed higher sensitivity (0.798 vs. 0.764; p = 0.0077). At the Youden-optimal point, sensitivity favored YOLO-TL (0.914 vs. 0.892; p = 0.041) with a non-significant specificity difference. Conclusions: Transfer learning may not improve overall AUC but can enhance practical performance at clinically crucial thresholds. By maintaining high detection rates while reducing false positives, the transfer learning model offers superior clinical utility. Same-modality cross-domain transfer learning is an efficient strategy for developing robust AI systems for rare diseases, supporting tools more readily acceptable in real-world screening workflows. en-copyright= kn-copyright= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakaharaRyuichi en-aut-sei=Nakahara en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtsukaYujiro en-aut-sei=Otsuka en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakeuchiKoichi en-aut-sei=Takeuchi en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraYusuke en-aut-sei=Nakamura en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkutaKunihiro en-aut-sei=Ikuta en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OsakiShuhei en-aut-sei=Osaki en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TamiyaHironari en-aut-sei=Tamiya en-aut-mei=Hironari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiwaShinji en-aut-sei=Miwa en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhshikaShusa en-aut-sei=Ohshika en-aut-mei=Shusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NishimuraShunji en-aut-sei=Nishimura en-aut-mei=Shunji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KaharaNaoaki en-aut-sei=Kahara en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=14 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=15 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=16 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Medical Informatics and Clinical Support Technology Development, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiology, Juntendo University School of Medicine 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=Plusman LCC kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Graduate School of Medicine, Nagoya University kn-affil= affil-num=7 en-affil=Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Musculoskeletal Oncology Service, Osaka International Cancer Institute, kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery, Kindai University Hospital kn-affil= affil-num=12 en-affil=Department of Orthopedic Surgery, Mizushima Central Hospital kn-affil= affil-num=13 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=malignant bone tumors kn-keyword=malignant bone tumors en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=transfer learning kn-keyword=transfer learning en-keyword=YOLO kn-keyword=YOLO en-keyword=radiographs kn-keyword=radiographs en-keyword=cross-domain learning kn-keyword=cross-domain learning en-keyword=diagnostic imaging kn-keyword=diagnostic imaging END start-ver=1.4 cd-journal=joma no-vol=61 cd-vols= no-issue=6 article-no= start-page=973 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250524 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Accuracy Verification of a Computed Tomography-Based Navigation System for Total Hip Arthroplasty in Severe Hip Dysplasia: A Simulation Study Using 3D-Printed Bone Models of Crowe Types II, III, and IV en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Objective: The use of computed tomography (CT)-based navigation systems has been shown to improve surgical accuracy in total hip arthroplasty. However, there is limited literature available about the application of CT-based navigation systems in severe hip dysplasia. This study aimed to evaluate the accuracy of a CT-based navigation system in patients with severe hip dysplasia using three-dimensional (3D)-printed bone models. Methods: 3D-printed bone models were generated from CT data of patients with severe hip dysplasia (Crowe type II, 10 hips; type III, 10 hips; and type IV, 10 hips). The accuracy of automatic segmentation, success rate, point-matching accuracy across different registration methods, and deviation values at reference points after registration were assessed. Results: For the combined cohort of Crowe II, III, and IV cases (n = 30), the Dice Similarity Coefficient and Jaccard Index were 0.99 ± 0.01 and 0.98 ± 0.02, respectively. These values indicate a high level of segmentation accuracy. The “Matching with true and false acetabulum + iliac crest” method achieved a 100% success rate across all groups, with mean deviations of 0.08 ± 0.28 mm in the Crowe II group, 0.12 ± 0.33 mm in the Crowe III group, and 0.14 ± 0.50 mm in the Crowe IV group (p = 0.572). In the Crowe IV group, the anterior superior iliac spine deviation was significantly lower using the “Matching with true and false acetabulum + iliac crest” method compared to the “Matching with true and false acetabulum” method (0.28 ± 0.49 mm vs. 3.29 ± 2.56 mm, p < 0.05). Conclusions: This study demonstrated the high accuracy of automatic AI-based segmentation, with a Dice Similarity Coefficient of 0.99 ± 0.01 and a Jaccard Index of 0.98 ± 0.02 in the combined cohort of Crowe type II, III, and IV cases (n = 30). The matching success rate was 100%, with additional points on the iliac crest, which improved matching accuracy and reduced deviations, depending on the case. en-copyright= kn-copyright= en-aut-name=OkudaRyuichiro en-aut-sei=Okuda en-aut-mei=Ryuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TetsunagaTomonori en-aut-sei=Tetsunaga en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaKazuki en-aut-sei=Yamada en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TetsunagaTomoko en-aut-sei=Tetsunaga en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KouraTakashi en-aut-sei=Koura en-aut-mei=Takashi 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=MasadaYasutaka en-aut-sei=Masada en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkazakiYuki en-aut-sei=Okazaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=total hip arthroplasty kn-keyword=total hip arthroplasty en-keyword=CT-based navigation kn-keyword=CT-based navigation en-keyword=bone model kn-keyword=bone model en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=Ortoma Treatment Solution kn-keyword=Ortoma Treatment Solution END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=42195 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Elucidation of puberulic acid–induced nephrotoxicity using stem cell-based kidney organoids en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent cases of acute kidney injury (AKI) in Japan have been linked to Beni-koji CholesteHelp supplements, with puberulic acid identified as a potential nephrotoxic contaminant. To address the need for a reliable in vitro nephrotoxicity testing platform, we developed a screening model using kidney organoids derived from adult rat kidney stem (KS) cells. The organoids were exposed to known nephrotoxicants, including cisplatin and gentamicin, to validate the system. Puberulic acid toxicity was evaluated in both KS cell-derived organoids and wild-type mice. The organoids recapitulated tubular injury induced by known nephrotoxins and showed significant Kim-1 mRNA upregulation. Puberulic acid-treated organoids and mice exhibited morphological features of acute tubular necrosis (ATN), mitochondrial damage, and reduced cytochrome c oxidase subunit IV (COX-IV) expression. Markers of oxidative stress and apoptosis, such as 8-hydroxy-2’-deoxyguanosine (8-OHdG) and cleaved caspase-3, were also elevated. These findings suggest that puberulic acid induces mitochondrial dysfunction and oxidative stress, leading to tubular cell death. Puberulic acid-induced nephrotoxicity was demonstrated using our kidney organoid model. KS cell-derived kidney organoids may provide a simple, reproducible, and rapid platform for nephrotoxicity assessment, which may complement conventional animal experiments. en-copyright= kn-copyright= en-aut-name=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UchidaNaruhiko en-aut-sei=Uchida en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraguchiSoichiro en-aut-sei=Haraguchi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Kidney organoid kn-keyword=Kidney organoid en-keyword=Kidney stem cell kn-keyword=Kidney stem cell en-keyword=Puberulic acid kn-keyword=Puberulic acid en-keyword=Nephrotoxicity kn-keyword=Nephrotoxicity en-keyword=Mitochondrial dysfunction kn-keyword=Mitochondrial dysfunction END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=11 article-no= start-page=e13960 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=Missing the Target: A Scoping Review of the Use of Percent Weight Loss for Obesity Management en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: To co-create comprehensive targets for obesity management, we need to understand the genesis and current use of percent weight loss targets in research. The goals of our scoping review are to (1) synthesize the literature on percent weight loss targets for adults with obesity and (2) discuss the percent weight loss targets in context with their health benefits.
Methods: We searched Cochrane, MEDLINE, and EMBASE for English language, pharmaceutical, and/or behavioral intervention studies in adults with obesity where the explicit aim of the study was weight reduction defined as a percent of body weight. Reviewers screened citations and extracted data including study characteristics.
Results: From 16,164 abstracts, we included 30 citations which were mostly randomized controlled trials (RCTs) (n = 17) or quasi-experimental studies (n = 12) published between 1992 and 2024. Most of the studies had target weight loss goals between 3% and 10% of body weight (n = 28), while n = 2 had body weight loss goals of 15% or 30%. The proportion of participants who met the percent weight loss target ranged from 5.9% (nutrition only study) to 85% (pharmaceutical study). The studies reported different reasons for targeting a percentage of weight loss such as disease-specific outcomes, reduced risk of disease, or patient-reported outcomes.
Conclusion: Percent weight loss targets were based on similar research and were often not feasible nor sustainable for most participants. The design of these interventions and evaluation of obesity management would benefit from more patient-focused parameters which could help to co-design comprehensive targets for research and practice. en-copyright= kn-copyright= en-aut-name=SherifaliDiana en-aut-sei=Sherifali en-aut-mei=Diana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RaceyMegan en-aut-sei=Racey en-aut-mei=Megan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Fitzpatrick‐LewisDonna en-aut-sei=Fitzpatrick‐Lewis en-aut-mei=Donna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GreenwayMichelle en-aut-sei=Greenway en-aut-mei=Michelle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SockalingamSanjeev en-aut-sei=Sockalingam en-aut-mei=Sanjeev kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TeohSoo Huat en-aut-sei=Teoh en-aut-mei=Soo Huat kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=PattonIan en-aut-sei=Patton en-aut-mei=Ian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MacklinDavid en-aut-sei=Macklin en-aut-mei=David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=van RossumElizabeth F. C. en-aut-sei=van Rossum en-aut-mei=Elizabeth F. C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=BusettoLuca en-aut-sei=Busetto en-aut-mei=Luca kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HornDeborah Bade en-aut-sei=Horn en-aut-mei=Deborah Bade kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Patricia NeceJ. D. en-aut-sei=Patricia Nece en-aut-mei=J. D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=LeguedeMorgan Emile Gabriel Salmon en-aut-sei=Leguede en-aut-mei=Morgan Emile Gabriel Salmon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=PearceNicole en-aut-sei=Pearce en-aut-mei=Nicole kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=Le RouxCarel en-aut-sei=Le Roux en-aut-mei=Carel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ArdJamy en-aut-sei=Ard en-aut-mei=Jamy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=AlbergaAngela S. en-aut-sei=Alberga en-aut-mei=Angela S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KaplanLee en-aut-sei=Kaplan en-aut-mei=Lee kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SharmaArya M. en-aut-sei=Sharma en-aut-mei=Arya M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=WhartonSean en-aut-sei=Wharton en-aut-mei=Sean kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University kn-affil= affil-num=2 en-affil=McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University kn-affil= affil-num=3 en-affil=McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University kn-affil= affil-num=4 en-affil=McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University kn-affil= affil-num=5 en-affil=Obesity Canada kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Clinical Medicine, Advanced Medical and Dental Institute, Universiti Sains Malaysia kn-affil= affil-num=8 en-affil=Obesity Canada kn-affil= affil-num=9 en-affil=Temerty Faculty of Medicine, University of Toronto kn-affil= affil-num=10 en-affil=Department of Internal Medicine, Division of Endocrinology, and Obesity Center CGG, Erasmus MC, University Medical Center Rotterdam kn-affil= affil-num=11 en-affil=Department of Medicine, University of Padova kn-affil= affil-num=12 en-affil=Center of Obesity Medicine and Metabolic Performance, Department of Surgery, University of Texas McGovern Medical School kn-affil= affil-num=13 en-affil=Obesity Action Coalition kn-affil= affil-num=14 en-affil=ABHispalis Spain, Alianza Hispana de Personas con Obesidad Latin America kn-affil= affil-num=15 en-affil=Obesity Canada kn-affil= affil-num=16 en-affil=School of Medicine, University College Dublin kn-affil= affil-num=17 en-affil=School of Medicine, Wake Forest University kn-affil= affil-num=18 en-affil=Department of Health, Kinesiology, and Applied Physiology, Concordia University kn-affil= affil-num=19 en-affil=Obesity, Metabolism and Nutrition Institute Massachusetts General Hospital and Harvard Medical School kn-affil= affil-num=20 en-affil=Department of Medicine, University of Alberta kn-affil= affil-num=21 en-affil=Temerty Faculty of Medicine, University of Toronto kn-affil= en-keyword=obesity management kn-keyword=obesity management en-keyword=percent body weight kn-keyword=percent body weight en-keyword=scoping review kn-keyword=scoping review en-keyword=target kn-keyword=target en-keyword=weight loss kn-keyword=weight loss END start-ver=1.4 cd-journal=joma no-vol=190 cd-vols= no-issue= article-no= start-page=127 end-page=137 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251128 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Basic Research II on Creative Educator Training Programs Based on Creativity and STEAM Education: Toward the Development of Educational Practice Role Models through the Organization of CE Competencies kn-title=創造性・STEAM 教育を基にした Creative Educator 育成プログラムに関する基礎研究Ⅱ ― CE コンピテンシーの整理を通した教育実践ロールモデル構築に向けて ― en-subtitle= kn-subtitle= en-abstract= kn-abstract=　創造性とSTEAM 教育を基盤としたCreative Educator（ CE）育成プログラムに関する研究では，CE を「身体的な感受や経験を通して創造性教育を担う教員」と定義し，その育成に必要なコンピテンシーを「身体的思考」「空間的思考」「批判的対話」「創造的な態度」とした。そこで本論では，授業における創造性育成の要素として四つ挙げ，創造性に関する先行研究を整理した。その結果，創造性の研究において四つの要素を以下の通り捉えられることを確認した。①身体を通した予期せぬ刺激「想定外」は，身体化された認知や素材との相互作用から生じる新しい思考を促す。②他者との関係性を意識した「場づくり」は，対話や協働を通して創造性を育む。③空間的思考に基づく「可視化」は，視覚情報の統合や変換により創造的イメージを支える。④「チャレンジ」は，自律的意思決定や創造的自信を高め，潜在的創造力の発揮を促す。 en-copyright= kn-copyright= en-aut-name=MATSUURAAi en-aut-sei=MATSUURA en-aut-mei=Ai kn-aut-name=松浦藍 kn-aut-sei=松浦 kn-aut-mei=藍 aut-affil-num=1 ORCID= en-aut-name=TUTUMIYoshiaki en-aut-sei=TUTUMI en-aut-mei=Yoshiaki kn-aut-name=堤祥晃 kn-aut-sei=堤 kn-aut-mei=祥晃 aut-affil-num=2 ORCID= en-aut-name=SONChande en-aut-sei=SON en-aut-mei=Chande kn-aut-name=宣昌大 kn-aut-sei=宣 kn-aut-mei=昌大 aut-affil-num=3 ORCID= en-aut-name=KIMURAHitoshi en-aut-sei=KIMURA en-aut-mei=Hitoshi kn-aut-name=木村仁 kn-aut-sei=木村 kn-aut-mei=仁 aut-affil-num=4 ORCID= en-aut-name=KIYOTATetsuo en-aut-sei=KIYOTA en-aut-mei=Tetsuo kn-aut-name=清田哲男 kn-aut-sei=清田 kn-aut-mei=哲男 aut-affil-num=5 ORCID= en-aut-name=INADAYoshihiko en-aut-sei=INADA en-aut-mei=Yoshihiko kn-aut-name=稲田佳彦 kn-aut-sei=稲田 kn-aut-mei=佳彦 aut-affil-num=6 ORCID= affil-num=1 en-affil=Faculty of Education, Okayama University kn-affil=岡山大学学術研究院教育学域 affil-num=2 en-affil=Kushiro Compulsory Education School, Hokkaido University of Education Late Course kn-affil=北海道教育大学附属釧路義務教育学校 後期課程 affil-num=3 en-affil=Osaka Kyoiku University Tennoji Junior High School kn-affil=大阪教育大学附属天王寺中学校 affil-num=4 en-affil=Shiga University Faculty of Education Elementary School kn-affil=滋賀大学教育学部附属小学校 affil-num=5 en-affil=Faculty of Education, Okayama University kn-affil=岡山大学学術研究院教育学域 affil-num=6 en-affil=Faculty of Education, Okayama University kn-affil=岡山大学学術研究院教育学域 en-keyword=創造性 kn-keyword=創造性 en-keyword=STEAM kn-keyword=STEAM en-keyword=コンピテンシー kn-keyword=コンピテンシー END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=6 article-no= start-page=1100 end-page=1111 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relation between obesity and health disorders as revealed by the J-ORBIT clinical information collection system directly linked to electronic medical records (J-ORBIT 1) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims/Introduction: Obesity triggers various health disorders, but information on these disorders in real-world settings remains limited. To address this knowledge gap, we developed a database directly linked to electronic medical records (EMRs). We here present the baseline data for this database, designated Japan Obesity Research Based on electronIc healTh Records (J-ORBIT).
Materials and Methods: Individuals with obesity disease diagnosed according to the criteria of the Japan Society for the Study of Obesity were registered in J-ORBIT from seven medical centers in Japan. We analyzed the relationship between body mass index (BMI), clinical characteristics, and the prevalence of obesity-related health disorders in this cohort.
Results: Data were obtained from 1,169 individuals, with a mean (±SD) age of 56.9 ± 15.3 years and a BMI of 31.4 ± 6.1 kg/m2. The prevalence of health disorders varied substantially across BMI categories, with a higher BMI being associated with an increased prevalence of hyperuricemia or gout, obstructive sleep apnea syndrome or obesity hypoventilation syndrome, musculoskeletal disorders, and obesity-related kidney disease, as well as with a higher frequency of both a family history of obesity and of a history of childhood obesity. Among individuals with a BMI of ≥25 kg/m2, the prevalence of hypertension and dyslipidemia did not increase with BMI, whereas that of glucose intolerance decreased with increasing BMI.
Conclusions: The J-ORBIT system, which collects clinical data in real time directly from EMRs, has the potential to provide insight into obesity and its associated health conditions, thereby contributing to improved care of affected individuals. en-copyright= kn-copyright= en-aut-name=NishikageSeiji en-aut-sei=Nishikage en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HirotaYushi en-aut-sei=Hirota en-aut-mei=Yushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakagawaYasushi en-aut-sei=Nakagawa en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshiiMasamichi en-aut-sei=Ishii en-aut-mei=Masamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhsugiMitsuru en-aut-sei=Ohsugi en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaedaEiichi en-aut-sei=Maeda en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshimuraKai en-aut-sei=Yoshimura en-aut-mei=Kai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoAkane en-aut-sei=Yamamoto en-aut-mei=Akane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakayoshiTomofumi en-aut-sei=Takayoshi en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatoTakehiro en-aut-sei=Kato en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YabeDaisuke en-aut-sei=Yabe en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsuhisaMunehide en-aut-sei=Matsuhisa en-aut-mei=Munehide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=EguchiJun en-aut-sei=Eguchi en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujitaYukihiro en-aut-sei=Fujita en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KumeShinji en-aut-sei=Kume en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MaegawaHiroshi en-aut-sei=Maegawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MiyakeKana en-aut-sei=Miyake en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShojimaNobuhiro en-aut-sei=Shojima en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YamauchiToshimasa en-aut-sei=Yamauchi en-aut-mei=Toshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YokoteKoutaro en-aut-sei=Yokote en-aut-mei=Koutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=UekiKohjiro en-aut-sei=Ueki en-aut-mei=Kohjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MiyoKengo en-aut-sei=Miyo en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OgawaWataru en-aut-sei=Ogawa en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= affil-num=1 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Center for Medical Informatics Intelligence, National Center for Global Health and Medicine kn-affil= affil-num=5 en-affil=Diabetes and Metabolism Information Center, Research Institute, National Center for Global Health and Medicine kn-affil= affil-num=6 en-affil=Division of Medical Informatics, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Diabetes, Endocrinology, and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Diabetes, Endocrinology, and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University kn-affil= affil-num=13 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Medicine, Shiga University of Medical Science kn-affil= affil-num=16 en-affil=Department of Medicine, Shiga University of Medical Science kn-affil= affil-num=17 en-affil=Department of Medicine, Shiga University of Medical Science kn-affil= affil-num=18 en-affil=Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine kn-affil= affil-num=21 en-affil=Chiba University kn-affil= affil-num=22 en-affil=Diabetes Research Center, Research Institute, National Center for Global Health and Medicine kn-affil= affil-num=23 en-affil=Center for Medical Informatics Intelligence, National Center for Global Health and Medicine kn-affil= affil-num=24 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= en-keyword=Body mass index kn-keyword=Body mass index en-keyword=Electronic medical records kn-keyword=Electronic medical records en-keyword=Obesity kn-keyword=Obesity END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=1568338 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250807 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A pilot transcriptomic study of a novel multitargeted BRT regimen for anti–MDA5 antibody-positive dermatomyositis: improving survival over conventional therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (MDA5-DM) is associated with severe outcomes, primarily due to rapidly progressive interstitial lung disease (RP-ILD), which is often refractory to standard therapies such as calcineurin inhibitors (e.g., tacrolimus) combined with cyclophosphamide (TC-Tx). This study evaluated the efficacy of a novel multitargeted regimen combining baricitinib, rituximab, and tacrolimus (BRT-Tx) in improving survival outcomes for MDA5-DM patients with poor prognostic factors.
Methods: Fourteen MDA5-DM patients with multiple adverse prognostic factors were studied. Seven received the BRT-Tx regimen, and the remaining seven, previously treated with TC-Tx, served as historical controls. Twelve-month survival was assessed. Transcriptome analysis was performed for six patients (BRT=3, TC=3), beginning with cluster analysis to evaluate whether changes in peripheral blood gene expression varied according to treatment or prognosis. Gene ontology analysis characterized expression profiles in survivors and distinguished treatment effects. Alterations in the type I, II, and III interferon signatures were also assessed.
Results: In the TC-Tx group, four of seven patients succumbed to RP-ILD, whereas all seven BRT-Tx patients survived the 12-month observation period. Only one BRT-Tx patient required combined rescue therapies, including plasma exchange, and one case of unexplained limbic encephalitis (LE) occurred. Cytomegalovirus reactivation was observed in both groups (BRT: 5/7; TC: 6/7). Transcriptomic analysis revealed no treatment-specific clustering of differentially expressed genes (DEGs) before and after therapy. However, survivors and nonsurvivors formed distinct clusters, with survivors showing significant posttreatment suppression of B-cell-related gene expression. Moreover, interferon signature scores were significantly lower after treatment in survivors than in nonsurvivors. BRT-Tx effectively suppressed B-cell-mediated immune responses and maintained a low interferon signature, while TC-Tx resulted in nonspecific gene suppression, and in nonsurvivors, an elevated interferon signature was observed.
Conclusion: BRT-Tx has the potential to improve survival in MDA5-DM patients by effectively targeting hyperactive immune pathways. The combination of rituximab and tacrolimus is expected to disrupt B-cell–T-cell interactions and reduce autoantibody production, whereas baricitinib may suppress both IFN and GM-CSF signaling, regulating excessive autoimmunity mediated by cells such as macrophages. Unlike TC-Tx, BRT-Tx avoids cyclophosphamide-associated risks such as infertility and secondary malignancies. Future randomized controlled trials are warranted to validate its efficacy and safety. en-copyright= kn-copyright= en-aut-name=TokunagaMoe en-aut-sei=Tokunaga en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakaiYu en-aut-sei=Nakai en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoYoshiharu en-aut-sei=Sato en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiratsukaMitori en-aut-sei=Hiratsuka en-aut-mei=Mitori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakatsueTakeshi en-aut-sei=Nakatsue en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaekiTakako en-aut-sei=Saeki en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UmayaharaTakatsune en-aut-sei=Umayahara en-aut-mei=Takatsune kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KoyamaYoshinobu en-aut-sei=Koyama en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Division of Rheumatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama Hospital kn-affil= affil-num=3 en-affil=DNA Chip Research Inc., Medical Laboratory kn-affil= affil-num=4 en-affil=DNA Chip Research Inc., Medical Laboratory kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Division of Rheumatology and Nephrology, Department of Internal Medicine, Nagaoka Red Cross Hospital kn-affil= affil-num=7 en-affil=Division of Rheumatology and Nephrology, Department of Internal Medicine, Nagaoka Red Cross Hospital kn-affil= affil-num=8 en-affil=Division of Dermatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama Hospital kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Division of Rheumatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama Hospital kn-affil= en-keyword=anti-MDA5 antibody-positive dermatomyositis (MDA5-DM) kn-keyword=anti-MDA5 antibody-positive dermatomyositis (MDA5-DM) en-keyword=JAK inhibitor kn-keyword=JAK inhibitor en-keyword=baricitinib kn-keyword=baricitinib en-keyword=rituximab kn-keyword=rituximab en-keyword=multitargeted treatment kn-keyword=multitargeted treatment en-keyword=IFN signature kn-keyword=IFN signature en-keyword=transcriptome analysis kn-keyword=transcriptome analysis END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=27481 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241111 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association between proteinuria and mineral metabolism disorders in chronic kidney disease: the Japan chronic kidney disease database extension (J-CKD-DB-Ex) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chronic kidney disease-mineral and bone disorder (CKD-MBD) are recognized as a systemic disease affecting the prognosis of patients with CKD. Proper management of CKD-MBD is important to improve the prognosis of patients with CKD. Although proteinuria is recognized as a poor prognostic factor in these patients, few reports have examined its association with CKD-MBD. We examined the association between proteinuria and CKD-MBD using data from the Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex). Among the patients registered in the J-CKD-DB-Ex, 30,977 with CKD stages G2–G5 who had serum creatinine, albumin, calcium, and phosphate concentrations measured at least once and urinalysis performed were included. The patients were divided into four groups (negative, 1+, 2+, and 3+) according to the degree of proteinuria. The association between proteinuria and CKD-MBD was examined by a logistic regression analysis. In a model adjusted for age, sex, diabetes, and the estimated glomerular filtration rate (eGFR), the odds ratio of the 3 + group compared with the negative group significantly increased to 2.67 (95% confidence interval, 2.29–3.13) for hyperphosphatemia, 2.68 (1.94–3.71) for hypocalcemia, and 1.56 (1.24–1.98) for hypomagnesemia. Proteinuria is associated with hyperphosphatemia, hypocalcemia, and hypomagnesemia in patients with CKD independently of eGFR. en-copyright= kn-copyright= en-aut-name=ShimamotoSho en-aut-sei=Shimamoto en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakaharaTakako en-aut-sei=Nakahara en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaShunsuke en-aut-sei=Yamada en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagasuHajime en-aut-sei=Nagasu en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KishiSeiji en-aut-sei=Kishi en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakashimaNaoki en-aut-sei=Nakashima en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsuruyaKazuhiko en-aut-sei=Tsuruya en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkadaHirokazu en-aut-sei=Okada en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TamuraKouichi en-aut-sei=Tamura en-aut-mei=Kouichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaritaIchiei en-aut-sei=Narita en-aut-mei=Ichiei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaruyamaShoichi en-aut-sei=Maruyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=YokooTakashi en-aut-sei=Yokoo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=WadaTakashi en-aut-sei=Wada en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= en-aut-name=KandaEiichiro en-aut-sei=Kanda en-aut-mei=Eiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KataokaHiromi en-aut-sei=Kataoka en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NangakuMasaomi en-aut-sei=Nangaku en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KashiharaNaoki en-aut-sei=Kashihara en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=NakanoToshiaki en-aut-sei=Nakano en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=2 en-affil=Department of Medical Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=3 en-affil=Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=4 en-affil=Department of Nephrology and Hypertension, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Nephrology and Hypertension, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Medical Informatics, Graduate School of Medical Science, Kyushu University kn-affil= affil-num=7 en-affil=Department of Nephrology, Nara Medical University kn-affil= affil-num=8 en-affil=Department of Nephrology, Faculty of Medicine, Saitama Medical University kn-affil= affil-num=9 en-affil=Department of Medical Science and Cardiorenal Medicine, Graduate School of Medicine, Yokohama City University kn-affil= affil-num=10 en-affil=Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Nagoya University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of General Medicine, Juntendo University Faculty of Medicine kn-affil= affil-num=13 en-affil=Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine kn-affil= affil-num=14 en-affil=Department of Nephrology and Rheumatology, Kanazawa University kn-affil= affil-num=15 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Health Data Science, Kawasaki Medical School kn-affil= affil-num=17 en-affil=Department of Medical Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=18 en-affil=Division of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Nephrology and Hypertension, Kawasaki Medical School kn-affil= affil-num=20 en-affil=Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University kn-affil= en-keyword=CKD-MBD kn-keyword=CKD-MBD en-keyword=Proteinuria kn-keyword=Proteinuria en-keyword=Hyperphosphatemia kn-keyword=Hyperphosphatemia en-keyword=Hypocalcemia kn-keyword=Hypocalcemia en-keyword=Hypomagnesemia kn-keyword=Hypomagnesemia en-keyword=J-CKD-DB-Ex kn-keyword=J-CKD-DB-Ex END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251128 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=p53-armed oncolytic adenovirus induces apoptosis in pancreatic cancer-associated stellate cells via macropinocytosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pancreatic ductal adenocarcinoma (PDAC)-associated pancreatic stellate cells (PSCs) promote PDAC tumor progression. Notably, PDAC tumors display enhanced macropinocytosis, resulting in enhanced uptake of extracellular particles, including nutrients and viruses. We previously demonstrated the therapeutic potential of telomerase-specific oncolytic adenoviruses OBP-301 and p53-armed OBP-702 against human PDAC cells. However, it remains unclear whether macropinocytosis promotes the virus sensitivity of PDAC-associated PSCs. Here, we show that PSCs activated by human PDAC cells (Panc-1 and BxPC-3) exhibit enhanced sensitivity to wild-type and oncolytic adenoviruses via enhanced macropinocytosis. The virus sensitivity of PSCs was analyzed for the infectivity, replication, and cytopathic activity of wild-type and oncolytic adenoviruses. PDAC-associated PSCs were more sensitive to wild-type and oncolytic adenoviruses than were control PSCs; this sensitivity was mediated by activation of macropinocytosis. In three-dimensional (3D) culture models, p53-armed OBP-702 decreased the viability of PDAC-associated PSCs more strongly than did non-armed OBP-301, reflecting induction of p53-mediated apoptosis. Co-inoculation of PSCs enhanced the growth of PDAC tumors, an effect that was attenuated by OBP-702-mediated p53 activation in the tumor stroma. Our results suggest that p53-armed oncolytic adenovirus OBP-702 eliminates PDAC-associated PSCs via enhancement of macropinocytosis-mediated virus entry and induction of p53-mediated apoptosis. en-copyright= kn-copyright= en-aut-name=NishiyamaTakeyoshi en-aut-sei=Nishiyama en-aut-mei=Takeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShojiRyohei en-aut-sei=Shoji en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KajiwaraYoshinori en-aut-sei=Kajiwara en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HashimotoNaoyuki en-aut-sei=Hashimoto en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiYosuke en-aut-sei=Takahashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YoshidaRyuichi en-aut-sei=Yoshida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TanakaHiroyoshi Y. en-aut-sei=Tanaka en-aut-mei=Hiroyoshi Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KanoMitsunobu R. en-aut-sei=Kano en-aut-mei=Mitsunobu R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MasamuneAtsushi en-aut-sei=Masamune en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Pharmaceutical Biomedicine, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=15 en-affil=Department of Pharmaceutical Biomedicine, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=16 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Oncolys BioPharma, Inc. kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=6 article-no= start-page=1839 end-page=1864 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250523 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Beneficial fiscal competition for foreign direct investment: transport infrastructure and economic integration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fiscal policy competition for a multinational enterprise (MNE) resulting in the same location of firms is widely recognized as harmful owing to losses of the host government’s budget without gains from firms’ behavior. In this study, we provide a plausible explanation why fiscal competition for an MNE keeping firms’ location choices unchanged can be beneficial by incorporating governments’ decisions on public investments in transport infrastructure, such as ports, which reduces the trade costs between two competing countries. Our model divides transport costs into infrastructure-independent and infrastructure-dependent; investments in infrastructure reduce infrastructure-dependent costs. We show that fiscal competition increases countries’ investments in infrastructure under low infrastructure-independent transport costs without affecting firms’ locations. Furthermore, we show that the host country benefits from fiscal competition, although it pays a subsidy to the MNE. Moreover, as investments in infrastructure generate positive spillovers, fiscal competition that improves transport infrastructure benefits non-host countries and improves global welfare. en-copyright= kn-copyright= en-aut-name=MoritaShigeo en-aut-sei=Morita en-aut-mei=Shigeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkoshiHirofumi en-aut-sei=Okoshi en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Faculty of Economics, Fukuoka University kn-affil= affil-num=2 en-affil=Faculty of Economics, Okayama University kn-affil= en-keyword=Fiscal competition for FDI kn-keyword=Fiscal competition for FDI en-keyword=Public infrastructure kn-keyword=Public infrastructure en-keyword=Transport costs kn-keyword=Transport costs en-keyword=Strategic complement kn-keyword=Strategic complement END start-ver=1.4 cd-journal=joma no-vol=786 cd-vols= no-issue= article-no= start-page=152753 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hydrogen-rich gas enhances mitochondrial membrane potential and respiratory function recovery in Caco-2 cells post-ischemia-reperfusion injury en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Ischemia-reperfusion (I/R) injury induces oxidative stress, leading to damage in highly susceptible intestinal tissues. Molecular hydrogen (H2) has shown therapeutic potential in I/R injuries, with our prior research showing its efficacy in improving outcomes in rat intestinal transplantation models. However, its impact on mitochondrial function remain insufficiently understood. This study aims to elucidate how H2 modulates mitochondrial function impaired by I/R injury.
Methods: To assess the effects of H2 on I/R injury, cells were divided into three groups: a control group, a hypoxic group (99 % N2, 1 % O2, without H2 for 3, 6, or 24 h), and a hypoxic-H2 group (99 % H2, 1 % O2, for the same durations). After treatment, cells were reoxygenated under normoxic conditions (21 % O2) for 1, 2, 4, or 6 h. Mitochondrial membrane potential, oxygen consumption, and ATP production were measured. Reactive oxygen species production and apoptotic and metabolic regulators were also assessed.
Results: H2 markedly promoting mitochondrial recovery following I/R injury, by enhancing ATP production, restoring mitochondrial membrane potential, and improving oxygen consumption. It also reduced ROS levels and suppressed pro-apoptotic signaling. Notably, H2 suppressed the expression of HIF1α and PDK1, suggesting that H2 may act upstream of hypoxia-driven signaling pathways. These changes promoted oxidative phosphorylation and overall cellular function during reperfusion.
Conclusions: Our findings reveal that H2 therapy supports mitochondrial function, suppresses ROS, and modulates hypoxia-driven pathways in I/R injury. These insights advance the understanding of H2's potential in addressing I/R injury and provide a foundation for its application in other hypoxia-related conditions. en-copyright= kn-copyright= en-aut-name=SeyaMizuki en-aut-sei=Seya en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AokageToshiyuki en-aut-sei=Aokage en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MengYing en-aut-sei=Meng en-aut-mei=Ying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirayamaTakahiro en-aut-sei=Hirayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshinoriKosaki en-aut-sei=Yoshinori en-aut-mei=Kosaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WatanabeAkihiro en-aut-sei=Watanabe en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaTaihei en-aut-sei=Yamada en-aut-mei=Taihei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Biological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Emergency, Disaster and Critical Care Medicine, Hyogo Medical University kn-affil= affil-num=10 en-affil=Department of Emergency, Disaster and Critical Care Medicine, Hyogo Medical University kn-affil= affil-num=11 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Intestinal ischemia-reperfusion injury kn-keyword=Intestinal ischemia-reperfusion injury en-keyword=Molecular hydrogen kn-keyword=Molecular hydrogen en-keyword=Hydrogen gas therapy kn-keyword=Hydrogen gas therapy en-keyword=Caco-2 cells kn-keyword=Caco-2 cells en-keyword=Mitochondrial function kn-keyword=Mitochondrial function en-keyword=Hypoxia-inducible factor-1α (HIF1α) kn-keyword=Hypoxia-inducible factor-1α (HIF1α) END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=14 article-no= start-page=4055 end-page=4070 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=CXCR4 Inhibition Induces Tumor Necrosis by Selectively Targeting the Proliferating Blood Vessels in Oral Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=The C-X-C chemokine receptor type 4 (CXCR4) is a G protein-coupled transmembrane receptor that contributes to tumor growth and angiogenesis. While prior studies have primarily focused on CXCR4 expression in cancer cells and its role in metastasis, a few have examined its involvement in tumor-associated vasculature. In this study, we reported for the first time that CXCR4 expression within the tumor vasculature is significantly associated with higher pathological grades of human oral squamous cell carcinoma (OSCC) (p<0.03). A previous study reported that inhibiting CXCR4 with AMD3100 induces tumor cell death and enhances the efficacy of the chemotherapeutic agent cisplatin. These findings suggest that CXCR4 is an important target for cancer treatment. However, the tumor vascular system is known to be heterogeneous within the tumor microenvironment (TME), which may influence the treatment outcomes. Therefore, this study aimed to explore the effect of CXCR4 antagonism on various blood vessels present within the oral squamous cell carcinoma (OSCC) tumor stroma. Although the efficiency of AMD3100 was not significant in MOC cancer cells, necrosis was induced in the TME when applied to a poorly differentiated OSCC model, highlighting the role of the TME. Notably, CXCR4 is found to be highly overlapped with CD105+ angiogenic tumor vessels among various vascular markers. Treatment with AMD3100 leads to a marked reduction in the CD105+ vessels and impairs the maturation of tumor micro-vessels, explaining the cause of observed necrosis. Thus, CXCR4 serves as a promising biomarker in OSCC, and its inhibition with AMD3100 offers the therapeutic potential, particularly in cases with advanced pathological grades. en-copyright= kn-copyright= en-aut-name=SoeYamin en-aut-sei=Soe en-aut-mei=Yamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EainHtoo Shwe en-aut-sei=Eain en-aut-mei=Htoo Shwe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaSaori en-aut-sei=Yoshida en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MinZin Zin en-aut-sei=Min en-aut-mei=Zin Zin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=4 en-affil=Preliminary Examination Room, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= en-keyword=CXCR4 kn-keyword=CXCR4 en-keyword=tumor angiogenesis kn-keyword=tumor angiogenesis en-keyword=chemokine receptors kn-keyword=chemokine receptors en-keyword=tumor microenvironment kn-keyword=tumor microenvironment en-keyword=oral squamous cell carcinoma (OSCC) kn-keyword=oral squamous cell carcinoma (OSCC) en-keyword=AMD3100 kn-keyword=AMD3100 END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue= article-no= start-page=106656 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=Voxel-based method for predicting workpiece chipping in end milling of unsintered pure iron-powder compact en-subtitle= kn-subtitle= en-abstract= kn-abstract=The miniaturization and high-torque requirements of electric motors in automotive and industrial applications have increased the adoption of axial-gap motors that employ unsintered pure iron-powder compacts. However, machining these brittle materials, particularly through end milling, typically results in significant workpiece chipping, which impedes cost-effective prototyping and small-lot production. Conventional chipping-prediction approaches, such as finite-element analysis and critical uncut chip-thickness methods, are limited by their computational costs and prediction accuracy, respectively. This study proposes a novel method for predicting chipping regions in the end milling of pure iron-powder compacts via voxel-based cutting-force simulation. The chipping risk at each voxel was evaluated based on the magnitude and direction of the simulated cutting force and local workpiece rigidity. Chipping was predicted when the risk index exceeded the threshold value. Cutting experiments were conducted to validate the proposed method, which shows good agreement between the predicted and observed chipping regions under various milling conditions. The results indicate that the proposed method can efficiently and accurately predict the chipping regions, thus outperforming conventional approaches in terms of computational cost. Although parameter tuning and threshold calibration were performed experimentally, the voxel-based framework enables practical prediction and analysis of transient machining phenomena. Future investigations shall focus on expanding the method to a wider range of machining conditions and integrating material-property considerations for further generalization. This approach offers a practical tool for optimizing machining parameters to minimize chipping and enhance the manufacturability of brittle powder compacts. en-copyright= kn-copyright= en-aut-name=TakayasuHiroto en-aut-sei=Takayasu en-aut-mei=Hiroto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanekoKazuki en-aut-sei=Kaneko en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShimizuJun en-aut-sei=Shimizu en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Science and Engineering, Ibaraki 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 Science and Engineering, Ibaraki University kn-affil= en-keyword=End milling kn-keyword=End milling en-keyword=Simulation kn-keyword=Simulation en-keyword=Voxel model kn-keyword=Voxel model en-keyword=Workpiece chipping kn-keyword=Workpiece chipping en-keyword=Brittle material kn-keyword=Brittle material en-keyword=Pure iron-powder compact kn-keyword=Pure iron-powder compact END start-ver=1.4 cd-journal=joma no-vol=98 cd-vols= no-issue= article-no= start-page=103224 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The vicious cycle between nutrient deficiencies and antibiotic-induced nutrient depletion at the host cell-pathogen interface: Coenzyme Q10 and omega-6 as key molecular players en-subtitle= kn-subtitle= en-abstract= kn-abstract=The increasing prevalence of antibiotic resistance and pathological inflammation underscores the importance of understanding the underlying biochemical and immune processes that govern the host-pathogen interface. Nutrient deficiency, compounded by antibiotic-induced nutrient depletion, forms a vicious cycle of overt inflammation, contributing to bacterial toxin translocation in human inter-organ and intra-organs milieus. Coenzyme Q10 (CoQ10) and omega-6 linoleic acid (LA 18:2ω6) are integral to cellular membrane integrity and immune defense. However, the complex enzymatic steps at the host cell-pathogen interface remain poorly understood. This study is particularly timely, as it explores these knowledge gaps, which can inform the development of nutritional and therapeutic strategies that modulate or target these mechanisms. Using an infectious-inflamed cell co-culture model of the gut-liver axis, we exposed triple cell co-cultures of human intestinal epithelial cells (T84), macrophage-like THP-1 cells, and hepatic cells (Huh7) to linoleic acid-producing Lactobacillus casei (L. casei) and Pseudomonas aeruginosa strain PAO1 (PAO1). The cultures were incubated for 6 h in medium with or without ceftazidime antibiotic. PAO1 and L. casei exerted opposing effects on the secretion of Th1 cytokines IL-1β, IL-6, and the Th 2-type cytokine IL-10. Inoculation with PAO1 decreased CoQ10 and linoleic acid levels compared to uninfected controls. L. casei restored cellular health and biofunctionality impaired by PAO1, indicating its benefit to the host's well-being. The antibiotic ceftazidime exerted dual effects, alleviating PAO1 toxicity while marginally disrupting the beneficial effects of L. casei. Our results show how the vicious cycle of nutrient deficiency and antibiotic-induced nutrient loss reinforces pathological inflammation at the host cell-pathogen interface and highlights the need for more appropriate targeted antibiotic use that preserves essential nutrients like CoQ10 and omega-6 fatty acids. Inflammatory responses driven by opportunistic pathogens and LA-producing bacteria represent opposing immunometabolic pathways that may provide insights into novel approaches for treating infection and reducing antibiotic resistance. en-copyright= kn-copyright= en-aut-name=GhadimiDarab en-aut-sei=Ghadimi en-aut-mei=Darab kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BlömerSophia en-aut-sei=Blömer en-aut-mei=Sophia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Şahi̇n KayaAysel en-aut-sei=Şahi̇n Kaya en-aut-mei=Aysel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KrügerSandra en-aut-sei=Krüger en-aut-mei=Sandra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RöckenChristoph en-aut-sei=Röcken en-aut-mei=Christoph kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SchäferHeiner en-aut-sei=Schäfer en-aut-mei=Heiner kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsuzakiShigenobu en-aut-sei=Matsuzaki en-aut-mei=Shigenobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BockelmannWilhelm en-aut-sei=Bockelmann en-aut-mei=Wilhelm kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= affil-num=2 en-affil=Faculty of Medicine, Christian-Albrechts-University of Kiel kn-affil= affil-num=3 en-affil=Department of Nutrition and Dietetics, Faculty of Health Sciences, Antalya Bilim University kn-affil= affil-num=4 en-affil=Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein kn-affil= affil-num=5 en-affil=Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein kn-affil= affil-num=6 en-affil=Laboratory of Molecular Gastroenterology & Hepatology, Christian-Albrechts-University & UKSH Campus Kiel kn-affil= affil-num=7 en-affil=Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University kn-affil= affil-num=9 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= en-keyword=Antibiotics kn-keyword=Antibiotics en-keyword=Coenzyme Q10 kn-keyword=Coenzyme Q10 en-keyword=Infection kn-keyword=Infection en-keyword=Inflammation kn-keyword=Inflammation en-keyword=Micronutrients kn-keyword=Micronutrients en-keyword=Oxidative stress kn-keyword=Oxidative stress END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251124 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of the small-field output factor in eclipse modeling methods using representative beam and measured data with averaged ionization chamber and diode detector measurements en-subtitle= kn-subtitle= en-abstract= kn-abstract=Beam modeling for radiotherapy treatment planning systems (RTPS) can be performed using representative beam data (RBD) or direct measurements. However, RBD typically excludes output factor (OPF) measurements for fields smaller than 3 × 3 cm2. The Eclipse treatment planning system addresses this limitation by incorporating measured OPF data for fields as small as 1 × 1 cm2. Although existing studies have primarily examined the accuracy of small-field OPFs for plastic scintillator detectors, studies directly comparing the OPF values obtained through RBD modeling with and without OPF measurements for small field sizes are limited. Therefore, this study proposes a novel measurement approach using data averaged from an ion chamber and diode detector for small-field dosimetry to provide critical insights into the integration of OPFs for these small field sizes in RBD-based beam modeling. We systematically evaluated the impact of small-field OPF measurements on beam modeling accuracy by comparing three distinct approaches: (1) RBD-based modeling without small-field OPF data, (2) RBD-based modeling incorporating measured small-field OPF data, and (3) modeling based solely on measured data, with and without the inclusion of 1 × 1 cm2 field sizes. In addition, we compared OPF values obtained from a W2 plastic scintillator detector with the averaged OPF values from a PinPoint 3D ion chamber and EDGE diode detector across multiple beam energies and flattening filter-free (FFF) configurations. Our analysis included field sizes ranging from 1 × 1 cm2 to 40 × 40 cm2. The results demonstrated that for square fields, OPF calculation differences between RBD modeling with and without measured data were < 1.5%, < 4.5%, and < 4.5% at 1 × 1 cm2, and < 0.5%, < 1.5%, and < 1.5% at 2  ×  2 cm2, respectively. The RBD group exhibited a trend in which the OPF difference increased with the expansion of the irradiation field size. Notably, the most significant variations between modeling approaches occurred along the upper jaw expansion direction in rectangular fields. This suggests that a thorough evaluation is necessary for modeling results with an OPF ≤  1 × 1 cm2. This study highlights the advantages and disadvantages of beam modeling using measured OPF and RBD, providing valuable insights for future facilities that rely solely on RBD for beam modeling. en-copyright= kn-copyright= en-aut-name=NishiokaKunio en-aut-sei=Nishioka en-aut-mei=Kunio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuniiYuki en-aut-sei=Kunii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanabeYoshinori en-aut-sei=Tanabe en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoYuichi en-aut-sei=Sakamoto en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamotoAkira en-aut-sei=Nakamoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakahashiShotaro en-aut-sei=Takahashi en-aut-mei=Shotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Radiology, Tokuyama Central Hospital kn-affil= affil-num=2 en-affil=Department of Radiology, Tokuyama Central Hospital kn-affil= affil-num=3 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Radiology, Tokuyama Central Hospital kn-affil= affil-num=5 en-affil=Department of Radiology, Tokuyama Central Hospital kn-affil= affil-num=6 en-affil=Department of Radiology, Tokuyama Central Hospital kn-affil= en-keyword=Beam modeling kn-keyword=Beam modeling en-keyword=Plastic scintillator detector kn-keyword=Plastic scintillator detector en-keyword=Small irradiation field kn-keyword=Small irradiation field en-keyword=Output factor kn-keyword=Output factor END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparative Analysis of a Dual DNA–RNA Panel and a DNA-Only Panel for Sarcoma: Real-World Data From a Nationwide Genomic Database en-subtitle= kn-subtitle= en-abstract= kn-abstract=Next-generation sequencing-based comprehensive cancer genomic profiling is promising in cancer management; however, most studies rely on tumor-only DNA panels from single institutions. In 2023, Japan introduced an insurance-covered cancer genomic profiling test—the GenMine TOP Cancer Genome Profiling System—a dual DNA–RNA panel with matched tumor–normal testing. This study evaluated its utility compared to a conventional DNA-only test (FoundationOne CDx) in managing sarcoma patients using a nationwide genetic profiling database provided by the Center for Cancer Genomics and Advanced Therapeutics. This study included 1046 patients registered between August 2023 and October 2024. The dual DNA–RNA test identified significantly more fusion genes (20.3% vs. 7.4%, p < 0.001) and therapeutically targetable kinase fusions (3.5% vs. 1.2%, p = 0.019) than the DNA-only test. Among patients with translocation-related sarcomas, histology-specific fusion genes were identified in 77.5% using the dual panel, compared to 40.0% with the DNA-only panel (p < 0.001). In non-gastrointestinal stromal tumor sarcomas, the dual test showed a trend toward higher rates of genotype-matched therapy (4.3% vs. 2.6%, p = 0.25) and a significantly higher rate of molecular targeted therapy (4.3% vs. 1.5%, p = 0.03). Additionally, 5.7% of patients had pathogenic germline variants identified through tumor–normal matched analysis. These findings suggest that a dual DNA–RNA panel with matched tumor–normal testing may improve diagnostic accuracy and inform treatment decisions in the routine clinical management of sarcoma. en-copyright= kn-copyright= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OsoneTatsunori en-aut-sei=Osone en-aut-mei=Tatsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=FutagawaMashu en-aut-sei=Futagawa en-aut-mei=Mashu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Center for Comprehensive Genomic Medicine, 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= en-keyword=comprehensive cancer genomic profiling (CGP) kn-keyword=comprehensive cancer genomic profiling (CGP) en-keyword=fusion genes kn-keyword=fusion genes en-keyword=gene alterations kn-keyword=gene alterations en-keyword=genotype-matched therapy kn-keyword=genotype-matched therapy en-keyword=potential germline variants (PGVs) kn-keyword=potential germline variants (PGVs) END start-ver=1.4 cd-journal=joma no-vol=386 cd-vols= no-issue= article-no= start-page=115145 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=Therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) with voluntary and forced exercise in a rat model of ischemic stroke en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ischemic stroke results in significant long-term disability and mortality worldwide. Although existing therapies, such as recombinant tissue plasminogen activator and mechanical thrombectomy, have shown promise, their application is limited by stringent conditions. Mesenchymal stem cell (MSC) transplantation, especially using SB623 cells (modified human bone marrow-derived MSCs), has emerged as a promising alternative, promoting neurogenesis and recovery. This study evaluated the effects of voluntary and forced exercise, alone and in combination with SB623 cell transplantation, on neurological and psychological outcomes in a rat model of ischemic stroke. Male Wistar rats that had undergone middle cerebral artery occlusion (MCAO) were divided into six groups: control, voluntary exercise (V-Ex), forced exercise (F-Ex), SB623 transplantation, SB623 + V-Ex, and SB623 + F-Ex. Voluntary exercise was facilitated using running wheels, while forced exercise was conducted on treadmills. Neurological recovery was assessed using the modified neurological severity score (mNSS). Psychological symptoms were evaluated through the open field test (OFT) and forced swim test (FST), and neurogenesis was assessed via BrdU labeling. Both exercise groups exhibited significant changes in body weight post-MCAO. Both exercises enhanced the treatment effect of SB623 transplantation. The forced exercise showed a stronger treatment effect on ischemic stroke than voluntary exercise alone, and the sole voluntary exercise improved depression-like behavior. The SB623 + F-Ex group demonstrated the greatest improvements in motor function, infarct area reduction, and neurogenesis. The SB623 + V-Ex group was most effective in alleviating depression-like behavior. Future research should optimize these exercise protocols and elucidate the underlying mechanisms to develop tailored rehabilitation strategies for stroke patients. en-copyright= kn-copyright= en-aut-name=NagaseTakayuki en-aut-sei=Nagase en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=SasadaSusumu en-aut-sei=Sasada en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawauchiSatoshi en-aut-sei=Kawauchi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YabunoSatoru en-aut-sei=Yabuno en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SugaharaChiaki en-aut-sei=Sugahara en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=MiyakeHayato en-aut-sei=Miyake en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SasakiTatsuya en-aut-sei=Sasaki en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawaiKoji en-aut-sei=Kawai en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TanimotoShun en-aut-sei=Tanimoto en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SaijoTomoya en-aut-sei=Saijo en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Ischemic stroke kn-keyword=Ischemic stroke en-keyword=Post-stroke depression kn-keyword=Post-stroke depression en-keyword=Regenerative medicine kn-keyword=Regenerative medicine en-keyword=Rehabilitation kn-keyword=Rehabilitation en-keyword=SB623 kn-keyword=SB623 END start-ver=1.4 cd-journal=joma no-vol=71 cd-vols= no-issue=11 article-no= start-page=938 end-page=943 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250402 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mechanical Subpulmonary Support in Fontan Circulation: A Juvenile Porcine Experimental Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mechanical cavopulmonary assist (CPA) remains challenging for failing Fontan circulation. This study aimed to evaluate the hemodynamic impact of partial CPA using a juvenile porcine model. Six pigs (30 kg) underwent the Fontan procedure using a handmade Y-shaped graft. Total CPA was established by assisting both superior vena cava (SVC) and inferior vena cava (IVC) flow to the pulmonary artery, whereas partial CPA assisted only IVC flow using a centrifugal pump. Cavopulmonary assist flow was set to 100%, 50%, or 25% of pre-Fontan cardiac output (CO). Hemodynamics at baseline, after total CPA, and after partial CPA were compared using paired t-tests. Total CPA with 100% CO support increased CO and reduced SVC and IVC pressures compared to baseline (CO, 1.03 vs. 2.36 L/min; SVC pressure, 16.3 vs. 9.5 mm Hg; IVC pressure, 17.3 vs. 9.3 mm Hg, p < 0.05 for all). Partial CPA with 25% CO support increased CO and decreased IVC pressure, though SVC pressure increased (CO, 1.03 vs. 1.52 L/min; SVC pressure, 16.3 vs. 20.5 mm Hg; IVC pressure, 17.3 vs. 11.5 mm Hg, p < 0.05 for all). Although total CPA achieved optimal hemodynamics, partial CPA with 25% CO flow was effective, suggesting a feasible, noninvasive solution for patients with failing Fontan physiology. en-copyright= kn-copyright= en-aut-name=SakodaNaoya en-aut-sei=Sakoda en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiYasuyuki en-aut-sei=Kobayashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EdakiDaichi en-aut-sei=Edaki en-aut-mei=Daichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KasaharaShingo en-aut-sei=Kasahara en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KotaniYasuhiro en-aut-sei=Kotani en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=From the Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=2 en-affil=From the Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=3 en-affil=From the Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=4 en-affil=From the Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=5 en-affil=From the Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=57 cd-vols= no-issue=2 article-no= start-page=49 end-page=80 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251125 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Evolution and Challenges of Consumer Behavior Models in the Age of AI Co-Existence en-subtitle= kn-subtitle= en-abstract= kn-abstract=　This study, based on a theoretical review, aims to elucidate elucidate the structural impact of changes in industrial and social systems, as well as advances in AI technologies, on consumer decision-making and purchasing behavior. It seeks to critically examine the limitations of traditional consumer behavior models that no longer adequately capture contemporary consumption patterns.
　Representative models such as AIDMA, AISAS, and SIPS demonstrated explanatory power within the technological and media contexts of their respective eras. However, in the current environment, where AI and algorithms not only deliver information but also shape the structure of choice, these models—built on the assumptions of linearity and rationality, are becoming increasingly insufficient.
　This paper provides a comprehensive overview of the theoretical evolution of consumer behavior models from the Mass Media Era to the Age of AI Coexistence. It highlights key limitations, including the neglect of nonlinearity; underestimation of emotional dimensions, such as empathy and resonance; and lack of theoretical responsiveness to the structural constraints imposed by algorithmic environments. Ultimately, this study serves as a theoretical starting point for a paradigm shift in consumer understanding, laying the groundwork for the future reconstruction of theory and he development of innovative marketing strategies in the age of intelligent systems. en-copyright= kn-copyright= en-aut-name=ShazadigulSawut en-aut-sei=Shazadigul en-aut-mei=Sawut kn-aut-name=夏扎提古丽沙吾提 kn-aut-sei=夏扎提古丽 kn-aut-mei=沙吾提 aut-affil-num=1 ORCID= affil-num=1 en-affil=Faculty of Humanities and Social Sciences, Okayama University kn-affil= en-keyword=Artificial Intelligence (AI) kn-keyword=Artificial Intelligence (AI) en-keyword=Consumer Behavior kn-keyword=Consumer Behavior en-keyword=Algorithm kn-keyword=Algorithm en-keyword=Decision-making kn-keyword=Decision-making en-keyword=Digital Marketing kn-keyword=Digital Marketing en-keyword=Social Media kn-keyword=Social Media 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=20250807 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Performance Assessment of ChatGPT for the Board Qualification Examination of the Japanese Society for Oral and Maxillofacial Radiology en-subtitle= kn-subtitle= en-abstract= kn-abstract=The aim of this study is to assess the performance and utility of ChatGPT for the board qualification examination of the Japanese Society for Oral and Maxillofacial Radiology (JSOMR). We assessed ChatGPT responses to 149 multiple-choice questions written in Japanese for the board qualification examination of the JSOMR for the 3 years from 2020 to 2022. The questions were directly entered into ChatGPT-3.5 and ChatGPT-4 models manually one by one as a prompt. The accuracy rate was calculated and classified by year, type of multiple-choice question, and level of intellectual ability, and significant differences were noted. The accuracy rate of GPT-3.5 for the 3 years was 45.0% (51.0% for 2020, 34.0% for 2021, and 50.0% for 2022), while the accuracy rate of GPT-4 was 68.5% (73.5% for 2020, 62.0% for 2021, and 70.0% for 2022) for the board qualification examination of the JSOMR. GPT-4 had a significantly higher accuracy rate than GPT-3.5 in each year. On performance classified by the type of multiple-choice questions, GPT-4 performed significantly better than GPT-3.5. However, neither model performed well with questions that required interpretation or knowledge of Japanese law. The performance of GPT-4 was significantly superior to GPT-3.5 in the board qualification examination of the JSOMR, suggesting that the use of Chat GPT, especially ChatGPT-4, would be effective as a tool for learning and preparing for the examination. en-copyright= kn-copyright= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawazuToshiyuki en-aut-sei=Kawazu en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HisatomiMiki en-aut-sei=Hisatomi en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkadaShunsuke en-aut-sei=Okada en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujikuraMamiko en-aut-sei=Fujikura en-aut-mei=Mamiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NambaYuri en-aut-sei=Namba en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaSuzuka en-aut-sei=Yoshida en-aut-mei=Suzuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshidaSaori en-aut-sei=Yoshida en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YanagiYoshinobu en-aut-sei=Yanagi en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AsaumiJunichi en-aut-sei=Asaumi en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Radiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Preliminary Examination Room, Okayama University Hospital kn-affil= affil-num=9 en-affil=Preliminary Examination Room, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=ChatGPT kn-keyword=ChatGPT en-keyword=GPT-3.5 kn-keyword=GPT-3.5 en-keyword=GPT-4 kn-keyword=GPT-4 en-keyword=Generative AI kn-keyword=Generative AI en-keyword=Large language model kn-keyword=Large language model en-keyword=Japanese Society for Oral and Maxillofacial Radiology kn-keyword=Japanese Society for Oral and Maxillofacial Radiology 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=20250924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=DSOK-0011 Potentially Regulates Circadian Misalignment and Affects Gut Microbiota Composition in Activity-Based Anorexia Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: Anorexia nervosa (AN) is a metabolic-psychiatric disorder characterized by severe weight loss, hypercortisolemia, and hypothalamic–pituitary–adrenal (HPA) axis activation. In this study, we investigated the effect of inhibiting cortisol regeneration via the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) on the pathophysiology of AN.
Method: Female C57BL/6J mice underwent a 7-day activity-based anorexia (ABA) paradigm, involving 3 h daily feeding and free access to wheels, until 25% body weight loss or experiment completion. Mice were orally treated once daily with a potent 11β-HSD1 inhibitor, DSOK-0011, or vehicle. Body weight, food intake, and activity transitions were recorded; plasma corticosterone and cholesterol levels were measured using a fluorometric assay; gut microbiota were analyzed using 16S rRNA sequencing; and hippocampal glial cells were analyzed using immunohistochemistry.
Results: DSOK-0011-treated mice exhibited a modest but significant increase in postprandial wheel-running activity compared to baseline (4–5 p.m., p = 0.018; 5–6 p.m., p = 0.043), whereas vehicle-treated mice showed higher preprandial activity (9–10 a.m., p = 0.0229). Gut microbiota analysis revealed increased alpha diversity in ABA mice, with a specific enrichment of the Lachnospiraceae family in the DSOK-0011 group. However, DSOK-0011 did not significantly affect body weight, food intake, corticosterone, and lipid levels, or hippocampal glial cell populations.
Conclusion: Inhibition of 11β-HSD1 by DSOK-0011 was associated with microbiota alterations and subtle shifts in activity timing under energy-deficient conditions. These findings suggest that peripheral glucocorticoid metabolism may influence microbial and behavioral responses in the ABA model, although its metabolic impact appears limited in the acute phase. en-copyright= kn-copyright= en-aut-name=KawaiHiroki en-aut-sei=Kawai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WadaNanami en-aut-sei=Wada en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakamotoShinji en-aut-sei=Sakamoto en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyazakiKenji en-aut-sei=Miyazaki en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoTaro en-aut-sei=Kato en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoriuchiYoshihiro en-aut-sei=Horiuchi en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KiriiHiroshi en-aut-sei=Kirii en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NguyenHoang Duy en-aut-sei=Nguyen en-aut-mei=Hoang Duy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HinotsuKenji en-aut-sei=Hinotsu en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhyaYoshio en-aut-sei=Ohya en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsadaTakahiro en-aut-sei=Asada en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YokodeAkiyoshi en-aut-sei=Yokode en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkahisaYuko en-aut-sei=Okahisa en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MiyazakiHaruko en-aut-sei=Miyazaki en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OohashiToshitaka en-aut-sei=Oohashi en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Sumitomo Pharma Co. Ltd kn-affil= affil-num=5 en-affil=Sumitomo Pharma Co. Ltd kn-affil= affil-num=6 en-affil=Sumitomo Pharma Co. Ltd kn-affil= affil-num=7 en-affil=Department of Animal Applied Microbiology, Okayama University Graduate School of Environmental, Life, Natural Science and Technology kn-affil= affil-num=8 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=11β-HSD1 kn-keyword=11β-HSD1 en-keyword=activity-based anorexia kn-keyword=activity-based anorexia en-keyword=anorexia nervosa kn-keyword=anorexia nervosa en-keyword=corticosterone kn-keyword=corticosterone en-keyword=eating disorders kn-keyword=eating disorders en-keyword=microbiota kn-keyword=microbiota END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=1 article-no= start-page=22 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251031 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Protective impact of landiolol against acute lung injury following hemorrhagic shock and resuscitation in rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hemorrhagic shock and resuscitation (HSR) induces pulmonary inflammation, leading to acute lung injury (ALI). Notably, blocking β1 receptors can lead to organ protection through anti‑inflammatory and anti‑apoptotic effects. Additionally, although the β1 receptor pathway is blocked by the β1 blocker, the β2 receptor pathway may be preserved and activate the 5' adenosine monophosphate‑activated protein kinase (AMPK) pathway. The present study aimed to examine whether administration of the β1 blocker landiolol could achieve lung protection in a model of HSR‑ALI, alongside improvements in inflammation and apoptosis. Male Sprague‑Dawley rats underwent hemorrhage keeping their mean arterial pressure at 30 mmHg for 1 h. Resuscitation by reinfusion was initiated to restore blood pressure to pre‑hemorrhage levels for >15 min, followed by a 45‑min stabilization period to create the HSR‑ALI model. Landiolol (100 mg/kg/min) or saline was continuously administered after resuscitation. The lung tissues, which were collected for assessing inflammation and apoptosis‑related damage, underwent analyses, including histological examination, neutrophil count, assessment of lung wet/dry weight ratio, detection of the mRNA levels of tumor necrosis factor‑α (TNF‑α) and inducible nitric oxide synthase (iNOS), identification of terminal deoxynucleotidyl transferase dUTP nick‑end labeling (TUNEL)‑positive cells, and evaluation of caspase‑3 expression. In addition, phosphorylated AMPKα (pAMPKα) expression was tested via western blotting. Compared with the HSR/saline group, the HSR/landiolol group demonstrated a reduction in lung tissue damage score, and significant reductions in neutrophil count, lung wet/dry weight ratio, lung TNF‑α and iNOS mRNA levels, TUNEL‑positive cells and cleaved caspase‑3 expression. Furthermore, landiolol administration following HSR treatment increased pAMPKα expression. No significant hypotension occurred between the HSR/landiolol and HSR/saline groups; and blood loss did not differ significantly between the groups. In conclusion, landiolol administration after HSR reduced lung inflammation and apoptosis, suggesting a potential improvement in tissue damage. Furthermore, pAMPKα activation in the HSR/landiolol group may be the mechanism underlying the pulmonary protective effects of landiolol. en-copyright= kn-copyright= en-aut-name=SakamotoRisa en-aut-sei=Sakamoto en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimizuHiroko en-aut-sei=Shimizu en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraRyu en-aut-sei=Nakamura en-aut-mei=Ryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LuYifu en-aut-sei=Lu en-aut-mei=Yifu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiYaqiang en-aut-sei=Li en-aut-mei=Yaqiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriEmiko en-aut-sei=Omori en-aut-mei=Emiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiToru en-aut-sei=Takahashi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Medical School kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Medical School kn-affil= affil-num=4 en-affil=Department of Human Anatomy, Shantou University Medical College kn-affil= affil-num=5 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Anesthesiology, Okayama Saidaiji Hospital kn-affil= affil-num=8 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=HSR kn-keyword=HSR en-keyword=lung injury kn-keyword=lung injury en-keyword=landiolol kn-keyword=landiolol en-keyword=β1 blocker kn-keyword=β1 blocker en-keyword=inflammation kn-keyword=inflammation en-keyword=apoptosis kn-keyword=apoptosis END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=436 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy of Pericapsular Nerve Group (PENG) block in preoperative rehabilitation (Prehabilitation) for patients with femoral neck fractures: study protocol for a randomized, placebo-controlled, double-blinded trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Despite surgery intervention for femoral neck fractures is recommended within 48 h of admission, achieving timely surgery presents challenges for patients with severe comorbidities, or in resource-limited settings. Preoperative rehabilitation (prehabilitation) reduces bedridden time, enhances mobility, and improves postoperative outcomes for patients scheduled for hip arthroplasty due to femoral neck fractures. However, prehabilitation is hindered by insufficient pain control. The pericapsular nerve group (PENG) block provides effective analgesia while preserving motor function. We designed a study to assess the efficacy of PENG block in facilitating prehabilitation for patients with femoral neck fractures who are scheduled for hip arthroplasty.
Methods This prospective randomized placebo-controlled double-blinded trial aims to enroll 100 patients with Garden 3 or 4 femoral neck fractures who are scheduled for hip arthroplasty. Participants will be randomly assigned to receive a PENG block with 0.375% ropivacaine (PENG group) or with normal saline (placebo group) before the initial prehabilitation session. The prehabilitation program comprises five items: Bed-sitting, Edge-sitting, Stand-up, Maintaining-standing, and Wheelchair-transfer, performed with the assistance of a single physical therapist. The primary outcome is the percentage of patients completing the entire prehabilitation program. Secondary outcomes during the initial prehabilitation session are the achievement of each program item and the Numerical Rating Scale (NRS) pain score. Other secondary outcomes include intraoperative bleeding amounts, thromboembolic events during postoperative day 0 to 7, postoperative 3-day cumulative Cumulated Ambulation Score (CAS), and discharge destination. The postoperative outcomes will be compared between subgroups of patients undergoing surgery within 48 h of admission and those undergoing surgery more than 48 h of admission.
Discussion This is the first study aiming to assess the efficacy of PENG block in prehabilitation for patients with femoral neck fractures who are scheduled for hip arthroplasty. PENG block could be beneficial, especially for patients facing delayed surgery, providing a potential treatment option during the waiting period.
Trial registration Japan Registry of Clinical Trials, jRCT1031220294, registered on August 26, 2022. en-copyright= kn-copyright= en-aut-name=JinZhuan en-aut-sei=Jin en-aut-mei=Zhuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugiyamaDaisuke en-aut-sei=Sugiyama en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HigoFumiya en-aut-sei=Higo en-aut-mei=Fumiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirataTakahiro en-aut-sei=Hirata en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiOsamu en-aut-sei=Kobayashi en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UedaKenichi en-aut-sei=Ueda en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Anesthesiology, Kameda Medical Center kn-affil= affil-num=3 en-affil=Department of Rehabilitation, Kameda Medical Center kn-affil= affil-num=4 en-affil=Department of Rehabilitation, Kameda Medical Center kn-affil= affil-num=5 en-affil=Department of Anesthesiology, Kameda Medical Center kn-affil= affil-num=6 en-affil=Department of Anesthesiology and Resuscitology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Anesthesiology, Kameda Medical Center kn-affil= en-keyword=Femoral neck fracture kn-keyword=Femoral neck fracture en-keyword=Hip fracture kn-keyword=Hip fracture en-keyword=PENG block kn-keyword=PENG block en-keyword=Pericapsular nerve group block kn-keyword=Pericapsular nerve group block en-keyword=Prehabilitation kn-keyword=Prehabilitation en-keyword=Preoperative mobilization kn-keyword=Preoperative mobilization en-keyword=Preoperative rehabilitation kn-keyword=Preoperative rehabilitation en-keyword=Randomized controlled trial kn-keyword=Randomized controlled trial en-keyword=Study protocol kn-keyword=Study protocol END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e06572 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250908 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Viral RNA Silencing Suppressor Modulates Reactive Oxygen Species Levels to Induce the Autophagic Degradation of Dicer‐Like and Argonaute‐Like Proteins en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mounting evidence indicates that viruses exploit elevated reactive oxygen species (ROS) levels to promote replication and pathogenesis, yet the mechanistic underpinnings of this viral strategy remain elusive for many viral systems. This study uncovers a sophisticated viral counter-defense mechanism in the Cryphonectria hypovirus 1 (CHV1)-Fusarium graminearum system, where the viral p29 protein subverts host redox homeostasis to overcome antiviral responses. That p29 directly interacts with and inhibits the enzymatic activity of fungal NAD(P)H-dependent FMN reductase 1 (FMR1), leading to increased ROS accumulation and subsequent autophagy activation is demonstrated. Strikingly, this ROS-induced autophagy selectively targets for degradation two core antiviral RNA silencing components against CHV1 in F. graminearum, Dicer-like 2 (DCL2) and Argonaute-like 1 (AGL1), thereby compromising the host's primary antiviral defense system. Genetic analysis confirms this coordinated hijacking of host machineries, as CHV1 shows enhanced accumulation in the FMR1 knockout and reduced accumulation in autophagy-deficient fungal strains. This work reveals a tripartite interplay among oxidative stress, autophagy, and RNA silencing that CHV1 manipulates through p29 multifunctional activity. These findings provide a model for how viruses coordinately regulate distinct host defense systems to optimize infection. en-copyright= kn-copyright= en-aut-name=ZhaiShiyu en-aut-sei=Zhai en-aut-mei=Shiyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PangTianxing en-aut-sei=Pang en-aut-mei=Tianxing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PengShiyu en-aut-sei=Peng en-aut-mei=Shiyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZouShenshen en-aut-sei=Zou en-aut-mei=Shenshen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DengZhiping en-aut-sei=Deng en-aut-mei=Zhiping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KangZhensheng en-aut-sei=Kang en-aut-mei=Zhensheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AndikaIda Bagus en-aut-sei=Andika en-aut-mei=Ida Bagus kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SunLiying en-aut-sei=Sun en-aut-mei=Liying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University kn-affil= affil-num=2 en-affil=State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University kn-affil= affil-num=3 en-affil=State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University kn-affil= affil-num=4 en-affil=Department of Plant Pathology, College of Plant Protection, Shandong Agricultural University kn-affil= affil-num=5 en-affil=Institute of Virology and Biotechnology, Zhejiang Academy of Agricultural Sciences kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=7 en-affil=State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University kn-affil= affil-num=8 en-affil=State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University kn-affil= affil-num=9 en-affil=State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University kn-affil= en-keyword=argonaute kn-keyword=argonaute en-keyword=autophagic degradation kn-keyword=autophagic degradation en-keyword=cryphonectria hypovirus 1 kn-keyword=cryphonectria hypovirus 1 en-keyword=dicer kn-keyword=dicer en-keyword=reactive oxygen species kn-keyword=reactive oxygen species en-keyword=RNA silencing suppressor kn-keyword=RNA silencing suppressor END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=234 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251114 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rotenone targets midbrain astrocytes to produce glial dysfunction-mediated dopaminergic neurodegeneration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Exposure to pesticides, such as rotenone or paraquat, is an environmental factor that plays an important role in the pathogenesis of Parkinson's disease (PD). Rotenone induces PD-like pathology and is therefore used to develop parkinsonian animal models. Dopaminergic neurotoxicity caused by rotenone has been attributed to the inhibition of mitochondrial complex I, oxidative stress and neuroinflammation; however, the mechanisms underlying selective dopaminergic neurodegeneration by rotenone remain unclear. To resolve this, we focused on glial diversity and examined whether the brain region-specific glial response to rotenone could determine the vulnerability of dopaminergic neurons using primary cultured neurons, astrocytes and microglia from the midbrain and striatum of rat embryos and rotenone-injected PD model mice. Direct neuronal treatment with low-dose rotenone failed to damage dopaminergic neurons. Conversely, rotenone exposure in the presence of midbrain astrocyte and microglia or conditioned media from rotenone-treated midbrain glial cultures containing astrocytes and microglia produced dopaminergic neurotoxicity, but striatal glia did not. Surprisingly, conditioned media from rotenone-treated midbrain astrocytes or microglia monocultures did not affect neuronal survival. We also demonstrated that rotenone targeted midbrain astrocytes prior to microglia to induce dopaminergic neurotoxicity. Rotenone-treated astrocytes produced secreted protein acidic and rich in cysteine (SPARC) extracellularly, which induced microglial proliferation, increase in IL-1β and TNF-α, and NF-κB (p65) nuclear translocation in microglia, resulting in dopaminergic neurodegeneration. In addition, rotenone exposure caused the secretion of NFAT-related inflammatory cytokines and a reduction in the level of an antioxidant metallothionein (MT)-1 from midbrain glia. Furthermore, we observed microglial proliferation and a decrease in the number of MT-positive astrocytes in the substantia nigra, but not the striatum, of low-dose rotenone-injected PD model mice. Our data highlight that rotenone targets midbrain astrocytes, leading to SPARC secretion, which promotes the neurotoxic conversion of microglia and leads to glial dysfunction-mediated dopaminergic neurodegeneration. en-copyright= kn-copyright= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IsookaNami en-aut-sei=Isooka en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikuokaRyo en-aut-sei=Kikuoka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImafukuFuminori en-aut-sei=Imafuku en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasaiKaori en-aut-sei=Masai en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TomimotoKana en-aut-sei=Tomimoto en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SogawaChiharu en-aut-sei=Sogawa en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SogawaNorio en-aut-sei=Sogawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitamuraYoshihisa en-aut-sei=Kitamura en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of Technology kn-affil= affil-num=9 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Pharmacotherapy, School of Pharmacy, Shujitsu University kn-affil= affil-num=11 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Rotenone kn-keyword=Rotenone en-keyword=Astrocyte kn-keyword=Astrocyte en-keyword=Microglia kn-keyword=Microglia en-keyword=SPARC kn-keyword=SPARC en-keyword=Parkinson's disease kn-keyword=Parkinson's disease END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=10 article-no= start-page=e0332595 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relationship between obesity indices and cognitive function in Japanese men: A cross-sectional study en-subtitle= kn-subtitle= en-abstract= kn-abstract=We aimed to investigate the associations among various obesity indices, including visceral (VAT) and subcutaneous adipose tissue (SAT), and cognitive function in community-dwelling Japanese men. This population-based cross-sectional study used data of 853 men who participated in the follow-up examinations of the Shiga Epidemiological Study of Subclinical Atherosclerosis. Among them, we analyzed data of 776 men who completed the Cognitive Abilities Screening Instrument (CASI) and had abdominal VAT and SAT areas measured using computed tomography. The VAT-to-SAT ratio (VSR) was calculated; participants were categorized into VSR quartiles. Using analysis of covariance, we computed crude and adjusted means of the CASI total and domain scores across VSR quartiles, adjusting for potential confounders. No significant differences were observed in total CASI scores among body mass index, VAT, or SAT quartiles. However, in the multivariable-adjusted model, participants in the lowest VSR quartile (Q1) had significantly lower CASI total scores than those in the third quartile (Q3) (Q1: 89.5, Q3: 90.9). Low VSR was independently associated with lower cognitive function in a community-based sample of middle-aged and older Japanese men. In summary, VSR may be associated with cognitive function in Japanese men, highlighting the importance of fat distribution in cognitive health and highlighting VSR as a useful indicator. en-copyright= kn-copyright= en-aut-name=MatsunoSatoshi en-aut-sei=Matsuno en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OzekiYuji en-aut-sei=Ozeki en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KadowakiSayaka en-aut-sei=Kadowaki en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=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=MiyagawaNaoko en-aut-sei=Miyagawa en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimaAzusa en-aut-sei=Shima en-aut-mei=Azusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=MiyazawaItsuko en-aut-sei=Miyazawa en-aut-mei=Itsuko 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=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=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=Department of Psychiatry, Shiga University of Medical Science kn-affil= affil-num=2 en-affil=Department of Psychiatry, 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=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=5 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=6 en-affil=Department of Preventive Medicine and Public Health, Keio University School of Medicine kn-affil= affil-num=7 en-affil=Department of Clinical Nursing, 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 Medicine, 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=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=13 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=38590 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Serum extracellular vesicles containing adenoviral E1A-DNA as a predictive biomarker for liquid biopsy in oncolytic adenovirus therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oncolytic adenoviruses replicate selectively in tumor cells and induce immunogenic cell death, but predictive biomarkers for early therapeutic response are lacking. This study evaluated extracellular vesicle-encapsulated adenoviral E1A-DNA (EV-E1A-DNA) as a minimally invasive biomarker for monitoring responses to telomerase-specific oncolytic adenoviruses OBP-301 and OBP-502. EVs were isolated from human and murine cancer cell lines and from the serum of treated mice using ultracentrifugation. EV-associated E1A-DNA levels were measured by quantitative polymerase chain reaction and found to correlate with cytotoxicity in vitro and tumor regression in vivo. In xenograft models, serum EV-E1A-DNA levels at 2 days post-treatment showed strong correlations with final tumor volume and survival, supporting their utility as an early predictive biomarker. In immunocompetent mice pre-immunized with wild-type adenovirus, free viral DNA was undetectable in serum due to neutralizing antibodies, whereas EV-E1A-DNA remained detectable. This “stealth effect” indicates that EVs protect viral components from immune clearance. These results demonstrate that EV-E1A-DNA is a sensitive and virus-specific biomarker that enables early assessment of therapeutic efficacy, even in the presence of antiviral immunity. This strategy offers a promising liquid biopsy approach for personalized monitoring of oncolytic virotherapy and may be applicable to other virus-based therapies. en-copyright= kn-copyright= en-aut-name=YagiChiaki en-aut-sei=Yagi en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HanzawaShunya en-aut-sei=Hanzawa en-aut-mei=Shunya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KadowakiDaisuke en-aut-sei=Kadowaki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaYusuke en-aut-sei=Yoshida en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakamotoMasaki en-aut-sei=Sakamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HamadaYuki en-aut-sei=Hamada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugimotoRyoma en-aut-sei=Sugimoto en-aut-mei=Ryoma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhtaniTomoko en-aut-sei=Ohtani en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KumonKento en-aut-sei=Kumon en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HashimotoMasashi en-aut-sei=Hashimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Oncolys BioPharma, Inc. kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Oncolytic adenovirus kn-keyword=Oncolytic adenovirus en-keyword=Extracellular vesicle kn-keyword=Extracellular vesicle en-keyword=Liquid biopsy kn-keyword=Liquid biopsy en-keyword=Predictive biomarker kn-keyword=Predictive biomarker en-keyword=Stealth effect kn-keyword=Stealth effect END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gemcitabine-induced neutrophil extracellular traps via interleukin-8-CXCR1/2 pathway promote chemoresistance in pancreatic cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, and chemoresistance poses a significant challenge in its treatment. Neutrophil extracellular traps (NETs) have emerged as key players in the tumour microenvironment, but their role in chemoresistance remains unclear.
Methods: We investigated the involvement of NETs in PDAC chemoresistance using patient tumour samples, in vitro assays with gemcitabine (GEM)-treated PDAC cells, and in vivo mouse models. We evaluated cytokine production, NET formation and tumour response to GEM, with or without the CXCR1/2 inhibitor navarixin.
Results: NETs are significantly accumulated in the tumours of PDAC patients exhibiting poor response to chemotherapy. GEM-treated PDAC cells secrete pro-inflammatory cytokines such as interleukin-8 (IL-8). IL-8 promote the formation of chemotherapy-induced NETs (chemoNETosis) through activation of CXCR 1/2 on neutrophils. Importantly, treatment with navarixin significantly suppressed chemoNETosis, restored sensitivity to GEM, and significantly reduced tumour growth in vivo.
Conclusions: Our findings reveal that NETs contribute to chemoresistance in PDAC and that IL-8–mediated chemoNETosis plays a pivotal role in this process. Inhibition of CXCR1/2-mediated NET formation enhances the efficacy of GEM. This approach may represent a promising therapeutic strategy for overcoming chemoresistance in PDAC. These results support further clinical investigation of anti-NETs therapies. en-copyright= kn-copyright= en-aut-name=NogiShohei en-aut-sei=Nogi en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaniguchiAtsuki en-aut-sei=Taniguchi en-aut-mei=Atsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YagiTomohiko en-aut-sei=Yagi en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KonoYoshiyasu en-aut-sei=Kono en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=11 article-no= start-page=1677 end-page=1685 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250819 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Role of Cytoreductive Nephrectomy in the Immune Checkpoint Inhibitor Era: A Multicenter Collaborative Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: We aimed to evaluate overall survival (OS) and determine the optimal timing of cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC) receiving immune checkpoint inhibitor (ICI)-based therapy.
Methods: This retrospective study reviewed medical records of 447 patients with mRCC treated with ICI at multiple Japanese institutions between January 2018 and August 2023. From this cohort, 178 patients with lymph node or distant metastases received either cytoreductive nephrectomy (CN group; n = 72) or ICI therapy without cytoreductive nephrectomy (non-CN group; n = 106) as first-line treatment.
Results: Median progression-free survival was 15.7 months, and median overall survival was 58.1 months. CN significantly improved OS, with the CN group's median OS not reached, compared to 29.6 months in the non-CN group (p = 0.01). Deferred CN also showed improved survival outcomes. Poor prognostic factors for immediate CN included International Metastatic Renal Cell Carcinoma Database Consortium poor risk, sarcomatoid differentiation, and a high neutrophil-to-lymphocyte ratio.
Conclusions: We developed a prognostic model to guide patient selection for CN, emphasizing the need for personalized treatment strategies. en-copyright= kn-copyright= en-aut-name=NukayaTakuhisa en-aut-sei=Nukaya en-aut-mei=Takuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakaharaKiyoshi en-aut-sei=Takahara en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ToyodaShingo en-aut-sei=Toyoda en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InokiLan en-aut-sei=Inoki en-aut-mei=Lan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukuokayaWataru en-aut-sei=Fukuokaya en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriKeiichiro en-aut-sei=Mori en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaenosonoRyoichi en-aut-sei=Maenosono en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsujinoTakuya en-aut-sei=Tsujino en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HirasawaYosuke en-aut-sei=Hirasawa en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HashimotoTakeshi en-aut-sei=Hashimoto en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KomuraKazumasa en-aut-sei=Komura en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujitaKazutoshi en-aut-sei=Fujita en-aut-mei=Kazutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OhnoYoshio en-aut-sei=Ohno en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ShirokiRyoichi en-aut-sei=Shiroki en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Urology, Fujita-Health University School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology, Fujita-Health University School of Medicine kn-affil= affil-num=3 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=4 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=5 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=6 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=10 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=11 en-affil=Department of Urology, Tokyo Medical University kn-affil= affil-num=12 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=13 en-affil=Department of Urology, Tokyo Medical University kn-affil= affil-num=14 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=15 en-affil=Department of Urology, Okayama University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=17 en-affil=Department of Urology, Tokyo Medical University kn-affil= affil-num=18 en-affil=Department of Urology, Fujita-Health University School of Medicine kn-affil= en-keyword=cytoreductive nephrectomy kn-keyword=cytoreductive nephrectomy en-keyword=IMDC classification kn-keyword=IMDC classification en-keyword=immune checkpoint inhibitor kn-keyword=immune checkpoint inhibitor en-keyword=neutrophil-to- lymphocyte ratio kn-keyword=neutrophil-to- lymphocyte ratio en-keyword=sarcomatoid differentiation kn-keyword=sarcomatoid differentiation END start-ver=1.4 cd-journal=joma no-vol=178 cd-vols= no-issue= article-no= start-page=106920 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=End-to-end time-dependent probabilistic assessment of landslide hazards using hybrid deep learning simulator en-subtitle= kn-subtitle= en-abstract= kn-abstract=Early warning detection of landslide hazards often requires real-time or near real-time predictions, which can be challenging due to the presence of multiple geo-uncertainties and time-variant external environmental loadings. The propagation of these uncertainties at the system level for understanding the spatiotemporal behavior of slopes often requires time-consuming numerical calculations, significantly hindering the establishment of an early warning system. This paper presents a hybrid deep learning simulator, which fuses parallel convolutional neural networks (CNNs) and long short-term memory (LSTM) networks through attention mechanisms, termed PCLA-Net, to facilitate time-dependent probabilistic assessment of landslide hazards. PCLA-Net features two novelties. First, it is capable of simultaneously handling both temporal and spatial information. CNNs specialize in interpreting spatial data, while LSTM excels in handling time-variant data. Coupled with two attention mechanisms, the two modules are combined to probabilistically predict the spatiotemporal behavior of slopes. Second, PCLA-Net realizes end-to-end predictions. In this paper, the Liangshuijing landslide in the Three Gorges Reservoir area of China is used to illustrate PCLA-Net. It is first validated followed by a comparison with existing techniques to demonstrate its improved predictive capabilities. The proposed PCLA-Net simulator can achieve the same level of accuracy with at least 50% reduction in computation resources. en-copyright= kn-copyright= en-aut-name=HuangMenglu en-aut-sei=Huang en-aut-mei=Menglu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraShin-ichi en-aut-sei=Nishimura en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShibataToshifumi en-aut-sei=Shibata en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangZe Zhou en-aut-sei=Wang en-aut-mei=Ze Zhou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Civil and Environmental Engineering, Okayama University kn-affil= affil-num=2 en-affil=Department of Civil and Environmental Engineering, Okayama University kn-affil= affil-num=3 en-affil=Department of Civil and Environmental Engineering, Okayama University kn-affil= affil-num=4 en-affil=Marie Skłodowska-Curie Fellow, Department of Engineering, University of Cambridge kn-affil= en-keyword=Spatial variability kn-keyword=Spatial variability en-keyword=Time-dependent reliability kn-keyword=Time-dependent reliability en-keyword=Convolutional neural networks kn-keyword=Convolutional neural networks en-keyword=Long short-term memory networks kn-keyword=Long short-term memory networks en-keyword=Attention mechanisms kn-keyword=Attention mechanisms en-keyword=Landslide hazards kn-keyword=Landslide hazards END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=185111 end-page=185124 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=Enhancing Protection Against Code Reuse Attacks on IoT Devices by Randomizing Function Addresses en-subtitle= kn-subtitle= en-abstract= kn-abstract=Most Internet of Things (IoT) devices currently in use are vulnerable to code reuse attacks because manufacturers typically deploy the same firmware across all devices. This uniformity enables attackers to craft a single exploit that can compromise multiple devices. To mitigate this risk, we propose a firmware diversification approach that creates multiple executable files with varying software compositions. Our approach introduces two complementary techniques: Function Address Reordering (FAR), which randomizes the order of functions within object files during compilation, and Object Address Reordering (OAR), which permutes the linking order of object files in the final executable. These techniques collectively diversify firmware instances without altering runtime behavior, making executing code reuse attacks significantly more difficult. By deploying firmware with diverse executable files, it is possible to enhance security without altering device behavior. We evaluate the effectiveness and limitations of the proposed methods when integrated into actual IoT firmware, assessing their resilience to code reuse attacks, impact on runtime behavior, and compilation overhead. Experimental results demonstrate that FAR and OAR significantly reduce the success rate of return-oriented programming attacks while incurring minimal performance overhead. This study offers a scalable, hardware-independent defense against code reuse attacks that increases resilience without a significant performance overhead, rendering it practical for widespread adoption in various IoT applications. en-copyright= kn-copyright= en-aut-name=SajiKazuma en-aut-sei=Saji en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamauchiToshihiro en-aut-sei=Yamauchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiSatoru en-aut-sei=Kobayashi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaniguchiHideo en-aut-sei=Taniguchi en-aut-mei=Hideo 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=Faculty 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=Code reuse attack kn-keyword=Code reuse attack en-keyword=IoT firmware kn-keyword=IoT firmware en-keyword=software diversity kn-keyword=software diversity en-keyword=function reordering kn-keyword=function reordering en-keyword=LLVM kn-keyword=LLVM END start-ver=1.4 cd-journal=joma no-vol=65 cd-vols= no-issue=3 article-no= start-page=101624 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=Spatial distribution estimation by considering the cross-correlation between components with indirect data using Gaussian process regression en-subtitle= kn-subtitle= en-abstract= kn-abstract=Generally, soil properties are measured only at limited locations. To rationally estimate the spatial distribution of soil properties, it is preferable to effectively use all available measurement data, including indirect data. We propose a Gaussian process regression with multiple random fields that considers the cross-correlation between one of the random fields of direct data and indirect data, and show the application to simulated data and actual measured data. In the application, the direct data are of CPT tip resistance (qc), which was obtained within a narrow area, and the indirect data are of shear wave velocity (Vs) obtained by surface wave exploration, which were obtained over a wide area. We estimate the spatial distribution of qc from the limited qc and wide area Vs data. The estimation accuracy of the proposed method is evaluated by cross-validation, and its effectiveness is discussed. en-copyright= kn-copyright= en-aut-name=TsudaYuto en-aut-sei=Tsuda en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaIkumasa en-aut-sei=Yoshida en-aut-mei=Ikumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishimuraShinichi en-aut-sei=Nishimura en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Postdoctoral Researcher, School of Integrative Science and Engineering, Tokyo City University kn-affil= affil-num=2 en-affil=Professor Emeritus, Department of Urban and Civil Engineering, Tokyo City University kn-affil= affil-num=3 en-affil=Department of Civil Environmental Engineering, Okayama University kn-affil= en-keyword=Shear wave velocity kn-keyword=Shear wave velocity en-keyword=Gaussian process regression kn-keyword=Gaussian process regression en-keyword=Random field kn-keyword=Random field en-keyword=CPT tip resistance kn-keyword=CPT tip resistance en-keyword=Indirect data kn-keyword=Indirect data END start-ver=1.4 cd-journal=joma no-vol=82 cd-vols= no-issue=10 article-no= start-page=1626 end-page=1637 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Redefining AT1 Receptor PET Imaging: Introducing the Radiotracer [18F]DR29 en-subtitle= kn-subtitle= en-abstract= kn-abstract=BACKGROUND: AT1R (angiotensin II type 1 receptors) are central to the renin-angiotensin system and are involved in regulating blood pressure and renal physiology. This study introduces [18F]DR29, a fluorine-18-labeled radiotracer for positron emission tomography imaging, to enable noninvasive visualization of AT1R expression. Its potential applications in understanding AT1R-associated renal processes are explored in healthy and hypertensive rat models.
METHODS: Radiolabeling was established, and biodistribution studies were conducted on healthy Wistar rats with and without the AT1R antagonist candesartan and transporter inhibitors. Dynamic positron emission tomography imaging assessed tracer specificity, and feasibility for renal AT1R quantification was explored using a hypertensive rat model.
RESULTS: [18F]DR29 was radiolabeled with a yield of 36±6%. High kidney uptake was observed, significantly reduced by candesartan (kidney-to-blood ratio, 0.43±0.01 versus 4.54±1.59 in vehicle, where vehicle refers to saline without any treatment). Transporter inhibition protocols targeting organic anion transporting polypeptides (liver) and organic anion transporters (kidneys) successfully reduced radiotracer clearance, increasing the specific accumulation of [18F]DR29 in the kidneys and improving renal imaging contrast. Positron emission tomography imaging revealed rapid kidney uptake and stable retention over 2 hours. In hypertensive rats, kidney uptake was higher, aligning with AT1R expression levels.
CONCLUSIONS: These results support [18F]DR29 as a promising tool for the noninvasive evaluation of renal AT1R expression in healthy and diseased states. The findings lay the groundwork for clinical translation, offering potential applications in diagnosing and managing kidney-related diseases, including hypertension and other conditions involving AT1R dysregulation. en-copyright= kn-copyright= en-aut-name=ChenXinyu en-aut-sei=Chen en-aut-mei=Xinyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuraHiroyuki en-aut-sei=Kimura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SasakiTakanori en-aut-sei=Sasaki en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KlimekKonrad en-aut-sei=Klimek en-aut-mei=Konrad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MühligSaskia en-aut-sei=Mühlig en-aut-mei=Saskia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Arias-LozaAnahi Paula en-aut-sei=Arias-Loza en-aut-mei=Anahi Paula kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NoseNaoko en-aut-sei=Nose en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YagiYusuke en-aut-sei=Yagi en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=RoweSteven P en-aut-sei=Rowe en-aut-mei=Steven P kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LapaConstantin en-aut-sei=Lapa en-aut-mei=Constantin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WernerRudolf A. en-aut-sei=Werner en-aut-mei=Rudolf A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HiguchiTakahiro en-aut-sei=Higuchi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Nuclear Medicine, Faculty of Medicine, University of Augsburg kn-affil= affil-num=2 en-affil=Agency for Health, Safety and Environment, Kyoto University kn-affil= affil-num=3 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Goethe University Frankfurt, University Hospital, Clinic for Radiology and Nuclear Medicine, Department of Nuclear Medicine kn-affil= affil-num=5 en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center (DZHI), University Hospital Würzburg kn-affil= affil-num=6 en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center (DZHI), University Hospital Würzburg kn-affil= affil-num=7 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Molecular Imaging and Therapeutics, Department of Radiology, School of Medicine, University of North Carolina, Chapel Hill kn-affil= affil-num=10 en-affil=Nuclear Medicine, Faculty of Medicine, University of Augsburg kn-affil= affil-num=11 en-affil=Department of Nuclear Medicine, LMU Hospital, Ludwig-Maximilians-University of Munich kn-affil= affil-num=12 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=angiotensin II type 1 receptor kn-keyword=angiotensin II type 1 receptor en-keyword=organic anion transporters kn-keyword=organic anion transporters en-keyword=organic anion transporting polypeptides kn-keyword=organic anion transporting polypeptides en-keyword=renal imaging kn-keyword=renal imaging en-keyword=renin-angiotensin system kn-keyword=renin-angiotensin system END start-ver=1.4 cd-journal=joma no-vol=81 cd-vols= no-issue= article-no= start-page=102548 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=Does innovation-driven policy optimize urban energy consumption? Evidence from China’s innovation-driven city pilot policies en-subtitle= kn-subtitle= en-abstract= kn-abstract=Restructuring energy consumption is essential for promoting green, low-carbon economic and societal development. Innovation-driven policies, particularly those implemented in pilot cities, play a crucial role in this transformation. This study conducts a theoretical analysis to examine how such policies influence urban energy-consumption structures. Using a multitime-point difference-in-differences model, it treats China’s national innovation-driven city pilot policies as a quasi-natural experiment. The results indicate that these policies significantly improve urban energy structures. Mechanism analyses reveal that the improvements occur mainly through green innovation and industrial upgrading. Heterogeneity analysis further indicates that the effects are more pronounced in cities with lower administrative tiers, more challenging geographical conditions, and stronger environmental priorities. These findings provide valuable policy insights for refining innovation-driven strategies, enhancing urban energy-consumption structures, and promoting sustainable economic development in China. en-copyright= kn-copyright= en-aut-name=CongYingnan en-aut-sei=Cong en-aut-mei=Yingnan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HouYufei en-aut-sei=Hou en-aut-mei=Yufei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=JiYuan en-aut-sei=Ji en-aut-mei=Yuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=CaiXiaojing en-aut-sei=Cai en-aut-mei=Xiaojing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Business School, China University of Political Science and Law kn-affil= affil-num=2 en-affil=School of Economics, Renmin University of China kn-affil= affil-num=3 en-affil=Business School, China University of Political Science and Law kn-affil= affil-num=4 en-affil=Graduate School of Humanities and Social Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Optogenetic Cancer Therapy Using the Light-Driven Outward Proton Pump Rhodopsin Archaerhodopsin-3 (AR3) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Medicines used for cancer treatment often cause serious side effects by damaging normal cells due to nonspecific diffusion. To address this issue, we previously developed an optical method to induce apoptotic cell death via intracellular pH alkalinization using the outward proton pump rhodopsin, Archaerhodopsin-3 (AR3) in various noncancer model cells in vitro and in vivo. In this study, we applied this method to cancer cells and tumors to evaluate its potential as an anticancer therapeutic strategy. First, we confirmed that AR3-expressing murine cancer cell lines (MC38, B16F10) showed apoptotic cell death upon green light irradiation, as indicated by increased levels of cell death and apoptosis-related markers. Next, we established stable AR3-expressing MC38 and B16F10 cells by using viral vectors. When these AR3-expressing cells were subcutaneously transplanted into C57BL/6 mice, the resulting tumors initially grew at a rate comparable to that of control tumors lacking AR3 expression or light stimulation. However, upon green light irradiation, AR3-expressing tumors exhibited either a marked reduction in size or significantly suppressed growth, accompanied by the induction of apoptosis signals and decreased proliferation signals. These results demonstrate that AR3-mediated cell death has potent antitumor effects both in vitro and in vivo. This optical method thus holds promise as a novel cancer therapy with potentially reduced side effects. en-copyright= kn-copyright= en-aut-name=NakaoShin en-aut-sei=Nakao en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KojimaKeiichi en-aut-sei=Kojima en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoKeita en-aut-sei=Sato en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KemmotsuNaoya en-aut-sei=Kemmotsu en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhuchiHideyo en-aut-sei=Ohuchi en-aut-mei=Hideyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SudoYuki en-aut-sei=Sudo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=37 cd-vols= no-issue=27-28 article-no= start-page=e70357 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251102 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Algebraic Connectivity Maximizing Regular Graphs: Special Case Analysis and Depth‐First Search en-subtitle= kn-subtitle= en-abstract= kn-abstract=The algebraic connectivity is an indicator of how well connected a graph is. It also characterizes the convergence speed of some dynamic processes over networks. In this paper, taking into account that homogeneous networks are modeled as regular graphs, we tackle the following problem: given a pair (𝑛, 𝑘) of positive integers such that 𝑘 is less than 𝑛 and kn is an even number, find a 𝑘-regular graph with 𝑛 vertices that have the maximum algebraic connectivity. We first consider some special cases and derive solutions through theoretical analysis. We next present depth-first search algorithms for solving the problem, which reduce the search space by making use of some known properties of the regular graph and the algebraic connectivity.We also show the results of execution of the proposed algorithms for the values of 𝑛 up to 12. en-copyright= kn-copyright= en-aut-name=KurahashiMasashi en-aut-sei=Kurahashi en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SalaaniNajd en-aut-sei=Salaani en-aut-mei=Najd kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MigitaTsuyoshi en-aut-sei=Migita en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiNorikazu en-aut-sei=Takahashi en-aut-mei=Norikazu 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=Polytech Sorbonne, Sorbonne University kn-affil= affil-num=3 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=algebraic connectivity kn-keyword=algebraic connectivity en-keyword=depth-first search kn-keyword=depth-first search en-keyword=optimization kn-keyword=optimization en-keyword=pruning kn-keyword=pruning en-keyword=regular graph kn-keyword=regular graph END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=11 article-no= start-page=1680 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251029 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Kidney Organoids: Current Advances and Applications en-subtitle= kn-subtitle= en-abstract= kn-abstract=Kidney organoids, derived from stem cells, including pluripotent stem cells and adult progenitor cells, have been reported as three-dimensional in vitro models that reflect key aspects of kidney development, structure, and function. Advances in differentiation protocols and tissue engineering have enabled the generation of organoids that exhibit nephron-like structures, including glomerular and tubular structures. Kidney organoids have been widely applied in several directions, including disease modeling and therapeutic screening, drug nephrotoxicity evaluation, and regenerative medicine. In particular, kidney organoids offer a promising platform for studying genetic kidney diseases, such as polycystic kidney disease and congenital anomalies of the kidney and urinary tract (CAKUT), by allowing patient-specific modeling for the analysis of pathophysiology and therapeutic screening. Despite several current limitations, such as incomplete maturation, lack of full nephron segmentation, and variability between protocols and cell conditions, further technological innovations such as microfluidics and bioengineering may refine kidney organoid systems. This review highlights recent advances in kidney organoid research, outlines major applications, and discusses future directions to enhance their physiological relevance, functional maturity, and translational integration into preclinical and clinical nephrology. en-copyright= kn-copyright= en-aut-name=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UchidaNaruhiko en-aut-sei=Uchida en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraguchiSoichiro en-aut-sei=Haraguchi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=kidney organoid kn-keyword=kidney organoid en-keyword=stem cell kn-keyword=stem cell en-keyword=disease modeling kn-keyword=disease modeling en-keyword=drug toxicity kn-keyword=drug toxicity en-keyword=drug screening kn-keyword=drug screening en-keyword=regenerative medicine kn-keyword=regenerative medicine END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=9 article-no= start-page=e92587 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250917 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Intranasal Administration of Semaphorin 3A Inhibitor in a Mouse Model of Olfactory Disorder en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study investigated the effects of intranasal administration of a semaphorin 3A inhibitor (Sema3A-I) in a mouse model of olfactory disorder, where olfactory sensory neuron (OSN) axons had been severely damaged. We performed axotomy (transection of OSN axons) of the OSNs in mice and administered Sema3A‑I intranasally to seven mice and saline to another seven mice. Following treatment, we assessed the thickness of the olfactory epithelium and the regeneration ratio of OSN axons. Intranasal administration of Sema3A-I did not significantly promote OSN regeneration, axonal outgrowth, or improve axonal projection compared to saline administration. Although Sema3A-I administration showed some promotion of axonal outgrowth, the difference was not statistically significant. Continuous subcutaneous administration of Sema3A-I in rats after axotomy promotes OSN regeneration and axonal outgrowth. Given that intranasal administration is minimally invasive, we believe that it may still be a feasible route when combined with additional treatment strategies. Further investigation into administration methods and therapeutic combinations is warranted. en-copyright= kn-copyright= en-aut-name=MuraiAya en-aut-sei=Murai en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NodaMinori en-aut-sei=Noda en-aut-mei=Minori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShimizuAiko en-aut-sei=Shimizu en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakaharaJunko en-aut-sei=Takahara en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MakiharaSeiichiro en-aut-sei=Makihara en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Division of Technical Support for Medical Science, Department of Comprehensive Technical Solutions, Okayama University kn-affil= affil-num=5 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University kn-affil= en-keyword=axon growth kn-keyword=axon growth en-keyword=intranasal administration kn-keyword=intranasal administration en-keyword=olfactory disorder kn-keyword=olfactory disorder en-keyword=olfactory sensory neurons kn-keyword=olfactory sensory neurons en-keyword=semaphorin3a kn-keyword=semaphorin3a END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=10 article-no= start-page=e70318 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250929 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effectiveness of Statins for Oxaliplatin‐Induced Peripheral Neuropathy: A Multicenter Retrospective Observational Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chemotherapy-induced peripheral neuropathy, including oxaliplatin-induced peripheral neuropathy (OIPN), can have a negative impact on patient quality of life for months or even years after discontinuation of chemotherapy. Statins are commonly used for lowering cholesterol; however, evidence indicates that statins have multiple pleiotropic effects. Although statins are anticipated to exert neuroprotective actions against OIPN, no large-scale investigations have been conducted in real-world clinical settings. Our investigation aimed to determine if statins protected against OIPN. This multicentre retrospective study enrolled Japanese patients with cancer, including those with colorectal cancer (CRC), who received oxaliplatin-containing chemotherapy between April 2009 and December 2019. Propensity score matching between groups was performed to assess the relationship between the occurrence of OIPN and statin use. Among the examined 2657 patients receiving oxaliplatin, 24.7% had Grade ≥ 2 OIPN. There was no significant difference in the incidence of OIPN between the statin and non-statin groups, even after propensity score matching. However, among the matched patients with CRC (n = 510), statin use was associated with a significantly lower incidence of Grade ≥ 2 OIPN than no statin use (19.8% vs. 28.3%, respectively; p = 0.029). Our findings indicate that statins may protect against OIPN in patients with CRC. en-copyright= kn-copyright= en-aut-name=TakechiKenshi en-aut-sei=Takechi en-aut-mei=Kenshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawashiriTakehiro en-aut-sei=Kawashiri en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MineKeisuke en-aut-sei=Mine en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UshioSoichiro en-aut-sei=Ushio en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HidaNoriko en-aut-sei=Hida en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MomoKenji en-aut-sei=Momo en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UchiyamaMasanobu en-aut-sei=Uchiyama en-aut-mei=Masanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchidaMami en-aut-sei=Uchida en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaMamoru en-aut-sei=Tanaka en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HidakaNoriaki en-aut-sei=Hidaka en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YasuiHideki en-aut-sei=Yasui en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=UedaMasahiro en-aut-sei=Ueda en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiiRyohei en-aut-sei=Fujii en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HashimotoMisaki en-aut-sei=Hashimoto en-aut-mei=Misaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SakamotoYasutaka en-aut-sei=Sakamoto en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=UyamaKana en-aut-sei=Uyama en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NiimuraTakahiro en-aut-sei=Niimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HanaiYuki en-aut-sei=Hanai en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TsuboyaAyaka en-aut-sei=Tsuboya en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=SuzukiKeisuke en-aut-sei=Suzuki en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KamiyamaNaoya en-aut-sei=Kamiyama en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=HagiwaraHiromi en-aut-sei=Hagiwara en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OkadaNaoto en-aut-sei=Okada en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=IshizawaKeisuke en-aut-sei=Ishizawa en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=Department of Drug Information Analysis, College of Pharmaceutical Sciences, Matsuyama University kn-affil= affil-num=2 en-affil=Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University kn-affil= affil-num=3 en-affil=Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University kn-affil= affil-num=4 en-affil=Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=5 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Research and Development, Graduate School of Pharmacy, SHOWA Medical University kn-affil= affil-num=7 en-affil=Department of Hospital Pharmaceutics, Graduate School of Pharmacy, SHOWA Medical University kn-affil= affil-num=8 en-affil=Department of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=9 en-affil=Department of Pharmacy, Fukuoka University Hospital kn-affil= affil-num=10 en-affil=Division of Pharmacy, Ehime University Hospital kn-affil= affil-num=11 en-affil=Division of Pharmacy, Ehime University Hospital kn-affil= affil-num=12 en-affil=Center for Clinical Research, Hamamatsu University Hospital kn-affil= affil-num=13 en-affil=Faculty of Pharmaceutical Sciences, Setsunan University kn-affil= affil-num=14 en-affil=Department of Pharmacy, Kansai Medical University Hospital kn-affil= affil-num=15 en-affil=Department of Pharmacy, Kansai Medical University Hospital kn-affil= affil-num=16 en-affil=Department of Pharmacy, Yokohama City University Hospital kn-affil= affil-num=17 en-affil=Department of Pharmacy, Yokohama City University Hospital kn-affil= affil-num=18 en-affil=Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences kn-affil= affil-num=19 en-affil=Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University kn-affil= affil-num=20 en-affil=Department of Pharmacy, Kawasaki Municipal Tama Hospital kn-affil= affil-num=21 en-affil=Innovation Center for Translational Research, National Center for Geriatrics and Gerontology kn-affil= affil-num=22 en-affil=Asahikawa Medical University Hospital kn-affil= affil-num=23 en-affil=Nagoya City University Hospital kn-affil= affil-num=24 en-affil=Pharmacy Department, Yamaguchi University Hospital kn-affil= affil-num=25 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=26 en-affil=Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences kn-affil= en-keyword=cancer kn-keyword=cancer en-keyword=colorectal cancer kn-keyword=colorectal cancer en-keyword=oxaliplatin kn-keyword=oxaliplatin en-keyword=peripheral neuropathy kn-keyword=peripheral neuropathy en-keyword=statins kn-keyword=statins END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250923 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=INF2-Related Charcot–Marie–Tooth Disease in a Japanese Cohort: Genetic and Clinical Insights en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: INF2 mutations cause focal segmental glomerulosclerosis (FSGS) and Charcot–Marie–Tooth disease (CMT). Accurate genetic diagnosis is critical, as INF2-related FSGS is typically resistant to immunotherapy yet rarely recurs after transplantation, and its associated neuropathy can mimic treatable immune-mediated disorders such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).
Methods: We performed a multicenter study investigating 3329 Japanese patients with inherited peripheral neuropathies/CMT who underwent gene panel sequencing or whole-exome analysis between 2007 and 2024. Clinical data, including electrophysiological assessments, were obtained from the patients' medical records.
Results: We identified six pathogenic INF2 variants in eight patients, all of which were located within the diaphanous inhibitory domain. Structural modeling revealed clustering of variants near the diaphanous autoregulatory domain-binding pocket, which is critical for INF2 autoinhibition. Clinically, all cases were sporadic, with a median age at neurological onset of 9 years. All patients exhibited lower limb weakness, and 6/8 (75%) had sensory disturbances. All patients also developed kidney dysfunction, with 7/8 (88%) progressing to end-stage renal disease at a median age of 15 years. Furthermore, all patients showed demyelinating neuropathy, and 2/8 (25%) received immunotherapy due to suspected immune-mediated neuropathy.
Conclusion: Although INF2 variants are a rare cause of CMT in Japan, they should be considered in pediatric patients with demyelinating neuropathy and early-onset proteinuria, even in the absence of a family history. Blood and urine tests assessing renal dysfunction can provide guidance for appropriate genetic testing. en-copyright= kn-copyright= en-aut-name=YanoChikashi en-aut-sei=Yano en-aut-mei=Chikashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AndoMasahiro en-aut-sei=Ando en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiguchiYujiro en-aut-sei=Higuchi en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YuanJun‐Hui en-aut-sei=Yuan en-aut-mei=Jun‐Hui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshimuraAkiko en-aut-sei=Yoshimura en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HobaraTakahiro en-aut-sei=Hobara en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagatomoRisa en-aut-sei=Nagatomo en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KojimaFumikazu en-aut-sei=Kojima en-aut-mei=Fumikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiramatsuYu en-aut-sei=Hiramatsu en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NozumaSatoshi en-aut-sei=Nozuma en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakamuraTomonori en-aut-sei=Nakamura en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SakiyamaYusuke en-aut-sei=Sakiyama en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsuokaChika en-aut-sei=Matsuoka en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KimuraTakashi en-aut-sei=Kimura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MiyazakiAyako en-aut-sei=Miyazaki en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KinjoChinatsu en-aut-sei=Kinjo en-aut-mei=Chinatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YokochiKenji en-aut-sei=Yokochi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamanakaNanami en-aut-sei=Yamanaka en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MatsudaNozomu en-aut-sei=Matsuda en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=SuichiTomoki en-aut-sei=Suichi en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HanaokaYoshiyuki en-aut-sei=Hanaoka en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KojimaHaruka en-aut-sei=Kojima en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=TodoKenichi en-aut-sei=Todo en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=TakashimaHiroshi en-aut-sei=Takashima en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= affil-num=1 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=2 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=3 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=4 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=5 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=6 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=7 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=8 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=9 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=10 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=11 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=12 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=13 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Neurology, Hyogo Medical University kn-affil= affil-num=16 en-affil=Department of Clinical Genetics, Hyogo Medical University kn-affil= affil-num=17 en-affil=Department of Clinical Genetics, Hyogo Medical University kn-affil= affil-num=18 en-affil=Department of Pediatrics, Toyohashi Municipal Hospital kn-affil= affil-num=19 en-affil=Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Neurology, Fukushima Medical University School of Medicine kn-affil= affil-num=21 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=22 en-affil=Department of Pediatrics, Kurashiki Central Hospital kn-affil= affil-num=23 en-affil=Department of Neurology, Tokyo Women's Medical University kn-affil= affil-num=24 en-affil=Department of Neurology, Tokyo Women's Medical University kn-affil= affil-num=25 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=26 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=27 en-affil=Department of Neurology, The University of Tokyo Hospital kn-affil= affil-num=28 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= en-keyword=Charcot-Marie- Tooth disease kn-keyword=Charcot-Marie- Tooth disease en-keyword=focal segmental glomerulosclerosis kn-keyword=focal segmental glomerulosclerosis en-keyword=INF2 kn-keyword=INF2 en-keyword=inherited peripheral neuropathies kn-keyword=inherited peripheral neuropathies en-keyword=neuropathy kn-keyword=neuropathy END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Refinement of interval approximations for fully commutative quivers en-subtitle= kn-subtitle= en-abstract= kn-abstract=A central challenge in the theory of multiparameter persistence modules lies in defining effective descriptors for representations of infinite or wild type. In this work, we propose a novel framework for analyzing interval approximations of fully commutative quivers, which offers a tunable trade-off between approximation resolution and computational complexity. Our approach is evaluated on commutative ladder modules of both finite and infinite type. For finite-type cases, we establish an efficient method for computing indecomposable decompositions using solely one-parameter persistent homology. For infinite-type cases, we introduce a new invariant that captures persistence in the second parameter by connecting standard persistence diagrams through interval approximations. Furthermore, we present several models for constructing commutative ladder filtrations, providing new insights into the behavior of random filtrations and demonstrating the utility of our framework in topological analysis of material structures. en-copyright= kn-copyright= en-aut-name=HiraokaYasuaki en-aut-sei=Hiraoka en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakashimaKen en-aut-sei=Nakashima en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ObayashiIppei en-aut-sei=Obayashi en-aut-mei=Ippei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=XuChenguang en-aut-sei=Xu en-aut-mei=Chenguang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Kyoto University kn-affil= affil-num=2 en-affil=Shimane University kn-affil= affil-num=3 en-affil=Okayama University kn-affil= affil-num=4 en-affil=Kyoto University kn-affil= en-keyword=Topological data analysis kn-keyword=Topological data analysis en-keyword=Multiparameter persistent homology kn-keyword=Multiparameter persistent homology en-keyword=Quiver representation kn-keyword=Quiver representation en-keyword=Zigzag persistence kn-keyword=Zigzag persistence en-keyword=Computational topology kn-keyword=Computational topology END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=20 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Natural Effects and Separable Effects: Insights into Mediation Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose of Review We compare natural effects and separable effects under nonparametric structural equation models with independent errors, highlighting their similarities and differences. By examining their required properties and sufficient conditions for identification, we aim to provide deeper insights into mediation analysis.
Recent Findings If certain assumptions about confounding, positivity, and consistency are met, we can identify natural direct and indirect effects under nonparametric structural equation models with independent errors. However, these effects have been criticized because they rely on a specific cross-world quantity, and the so-called cross-world independence assumption cannot be empirically verified. Furthermore, interventions on the mediator may sometimes be challenging to even conceive. As an alternative approach, separable effects have recently been proposed and applied in mediation analysis, often under finest fully randomized causally interpretable structured tree graph models. These effects are defined without relying on any cross-world quantities and are claimed to be identifiable under assumptions that are testable in principle, thereby addressing some of the challenges associated with natural direct and indirect effects.
Summary To conduct meaningful mediation analysis, it is crucial to clearly define the research question of interest, and the choice of methods should align with the nature of the question and the assumptions researchers are willing to make. Examining the underlying philosophical perspectives on causation and manipulation can provide valuable insights. en-copyright= kn-copyright= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShinozakiTomohiro en-aut-sei=Shinozaki en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoEiji en-aut-sei=Yamamoto en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Interfaculty Initiative in Information Studies, the University of Tokyo kn-affil= affil-num=3 en-affil=Okayama University of Science kn-affil= en-keyword=Causality kn-keyword=Causality en-keyword=Counterfactuals kn-keyword=Counterfactuals en-keyword=Cross-world independence assumption kn-keyword=Cross-world independence assumption en-keyword=Directed acyclic graphs kn-keyword=Directed acyclic graphs en-keyword=Mediation analysis kn-keyword=Mediation analysis en-keyword=Nonparametric structural equation models with independent errors kn-keyword=Nonparametric structural equation models with independent errors 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=20251013 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Creep damage parameters based on the distribution of cavities on grain boundaries en-subtitle= kn-subtitle= en-abstract= kn-abstract=When polycrystalline heat-resistant steels are subjected to static or cyclic loading at high temperatures, they can exhibit various fracture modes and processes. This paper begins by outlining representative methods for life assessment under creep-dominated conditions. It then discusses the fracture processes and the underlying mechanisms. Under creep-dominated conditions, the initiation and growth of cavities serve as the primary form of material damage, making their quantitative assessment essential. Several parameters have been proposed to evaluate cavity distributions quantitatively. However, the relationship between these parameters and the actual cavity distribution in materials, as well as their physical significance, has remained unclear. In this study, a simple cavity distribution model was employed to clarify these issues. The results suggest that the area fraction of cavities is an appropriate damage evaluation parameter for transgranular fracture, while the fraction of cavities on grain boundary line is suitable for intergranular fracture. en-copyright= kn-copyright= en-aut-name=TadaNaoya en-aut-sei=Tada en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Creep kn-keyword=Creep en-keyword=cavity kn-keyword=cavity en-keyword=grain boundary kn-keyword=grain boundary en-keyword=damage parameter kn-keyword=damage parameter en-keyword=modelling kn-keyword=modelling en-keyword=geometrical analysis kn-keyword=geometrical analysis en-keyword=probabilistic analysis kn-keyword=probabilistic analysis END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251014 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparative analysis of interactions between five strains of Pseudomonas syringae pv. tabaci and Nicotiana benthamiana en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pseudomonas syringae pv. tabaci 6605 (Pta 6605), the agent of wildfire disease in tobacco, has been used as a model strain for elucidating the virulence mechanisms of Pta. However, the host genes involved in resistance or susceptibility to Pta remain largely unknown. Nicotiana benthamiana is a model plant species in the Solanaceae family and is useful in functional analyses of genes. We herein compared five Pta strains (6605, 6823, 7372, 7375, and 7380) in terms of their phenotypes on medium and interactions with N. benthamiana. Pta 6605 and Pta 6823 showed more active proliferation than the other strains in a high cell density culture. Moreover, Pta 6605 exhibited markedly higher swarming motility than the other strains. In inoculated leaves of N. benthamiana, Pta 6605 and Pta 6823 caused more severe disease symptoms and proliferated to a higher cell density than the other strains. However, Pta 6823 as well as Pta 7372 and Pta 7380 induced the high accumulation of salicylic acid (SA). Moreover, the inoculations of Pta 6823 and Pta 7372 resulted in the upregulation of ethylene biosynthesis genes. On the other hand, Pta 6605 induced neither SA accumulation nor the expression of ethylene biosynthesis genes, and suppressed the expression of jasmonate biosynthesis genes. Moreover, chlorosis was clearly induced in the upper uninoculated leaves of Pta 6605-infected plants. These results suggest that Pta 6605 escapes from or suppresses plant immune systems and, thus, is the most virulent on N. benthamiana among the five strains tested. en-copyright= kn-copyright= en-aut-name=NakaoYuna en-aut-sei=Nakao en-aut-mei=Yuna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsaiShuta en-aut-sei=Asai en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuiHidenori en-aut-sei=Matsui en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IchinoseYuki en-aut-sei=Ichinose en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatouShinpei en-aut-sei=Katou en-aut-mei=Shinpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Science and Technology, Shinshu University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Science and Technology, Shinshu University kn-affil= en-keyword=Chlorosis kn-keyword=Chlorosis en-keyword=Nicotiana benthamiana kn-keyword=Nicotiana benthamiana en-keyword=Phytohormones kn-keyword=Phytohormones en-keyword=Pseudomonas syringae pv. tabaci kn-keyword=Pseudomonas syringae pv. tabaci END start-ver=1.4 cd-journal=joma no-vol=150 cd-vols= no-issue= article-no= start-page=110530 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Surrogate-assisted motion planning and layout design of robotic cellular manufacturing systems en-subtitle= kn-subtitle= en-abstract= kn-abstract=A surrogate-assisted multi-objective evolutionary algorithm is proposed for simultaneous optimization of robot motion planning and layout design in robotic cellular manufacturing systems. A sequence-pair is used to represent the layout of components in a robotic cell to avoid overlapping in the evolutionary computation. The robot motion planning with Rapidly exploring Random Trees Star (RRT*) is applied to compute the total operation time of a robot arm for each layout. Non-dominated Sorting Genetic Algorithm II (NSGA-II) is used to minimize the total required layout area and the operation time for a robot arm. The proposed surrogate model can estimate the robot’s operation time with 98% of accuracy without explicit computations of the motion planning algorithm. The experimental results with a physical 6 Degree of Freedom (DOF) manipulator show that the total computation time is approximately 1/400, significantly shorter than the conventional methods. en-copyright= kn-copyright= en-aut-name=KawabeTomoya en-aut-sei=Kawabe en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiTatsushi en-aut-sei=Nishi en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiuZiang en-aut-sei=Liu en-aut-mei=Ziang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiwaraTomofumi en-aut-sei=Fujiwara en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life and Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life and Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life and Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life and Natural Science and Technology, Okayama University kn-affil= en-keyword=Robotics kn-keyword=Robotics en-keyword=Cellular manufacturing kn-keyword=Cellular manufacturing en-keyword=Layout design kn-keyword=Layout design en-keyword=Sequence-pair kn-keyword=Sequence-pair en-keyword=Motion planning kn-keyword=Motion planning en-keyword=Surrogate optimization kn-keyword=Surrogate optimization en-keyword=Machine learning kn-keyword=Machine learning en-keyword=Artificial intelligence kn-keyword=Artificial intelligence END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=9 article-no= start-page=251152 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=On weapons allometry and the form of sexual selection en-subtitle= kn-subtitle= en-abstract= kn-abstract=The study of trait scaling with body size (allometry) has a long history, and it has been argued that positive static allometry is an indicator of directional sexual selection. However, a range of allometries exists for sexually selected traits, and modelling shows this variation can be generated by altering the form of selection (fitness functions) on the trait and/or body size. Interestingly, in all models, positive allometry appears to emerge only when there is directional selection on trait size. Here, we report on a sexually selected trait that shows strong positive static allometry and yet appears to be under stabilizing selection. This surprising finding suggests the evolution of trait scaling is even more nuanced than currently appreciated. en-copyright= kn-copyright= en-aut-name=ShinoharaHironori en-aut-sei=Shinohara en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SharmaManmohan D. en-aut-sei=Sharma en-aut-mei=Manmohan D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PennellTanya M. en-aut-sei=Pennell en-aut-mei=Tanya M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkadaKensuke en-aut-sei=Okada en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HoskenDavid J. en-aut-sei=Hosken en-aut-mei=David J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Center for Ecology and Conservation, University of Exeter, Cornwall Campus kn-affil= affil-num=2 en-affil=Center for Ecology and Conservation, University of Exeter, Cornwall Campus kn-affil= affil-num=3 en-affil=Center for Ecology and Conservation, University of Exeter, Cornwall Campus kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Center for Ecology and Conservation, University of Exeter, Cornwall Campus kn-affil= en-keyword=inbreeding kn-keyword=inbreeding en-keyword=selection kn-keyword=selection en-keyword=beetle kn-keyword=beetle en-keyword=Gnatocerus kn-keyword=Gnatocerus END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue= article-no= start-page=57 end-page=65 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=Rectal Swab–based Targeted Prophylactic Antibiotics Reduce Infectious Complications After Transrectal Prostate Biopsy: A Systematic Review and Meta-analysis of Randomized Controlled Trials en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and objective: Transperineal ultrasound-guided prostate biopsy is the recommended approach in guidelines, while transrectal ultrasound-guided prostate biopsy (TRUS-PB) is still widely used to diagnose prostate cancer (PCa); however, it is associated with a significant rate of infectious complications. We aimed to assess the efficacy of targeted prophylactic antibiotics (TPAs), based on rectal swabs, in reducing the incidence of infectious complications after TRUS-PB compared with empiric prophylactic antibiotics.
Methods: PubMed, Web of Science, and Scopus were queried in December 2024 for randomized controlled trials (RCTs) comparing infectious complications between patients who received TPAs based on rectal swab culture before TRUS-PB and those who received empiric prophylactic antibiotics before TRUS-PB (PROSPERO: CRD42024523794). The primary outcomes were the incidence rates of febrile urinary tract infection (fUTI) and sepsis.
Key findings and limitations: Overall, nine RCTs (n = 3002) were included in our analyses. The incidence of fUTI was approximately half as high in patients who received TPAs as in those who received empiric prophylactic antibiotics (n = 3002, 2.7% vs 5.2%, risk ratio [RR]: 0.54, 95% confidence interval [CI]: 0.36–0.81, p = 0.003). Based on these pooled incidence rates, the number of patients needed to treat to prevent fUTI after TRUS-PB was 40; however, there was no statistically significant difference in the incidence of sepsis between patients receiving TPAs and those who received empiric antibiotic prophylaxis (n = 2735, 1.3% vs 1.8%, RR: 0.74, 95% CI: 0.31–1.75, p = 0.4).
Conclusions and clinical implications: TPAs based on rectal swab culture significantly reduces the incidence of fUTI in patients who undergo TRUS-PB for PCa diagnosis compared with that in patients who receive empiric prophylactic antibiotics; however, there is insufficient evidence to assess its effect on the risk of sepsis. We recommend, based on the clinically relevant reduction in the incidence of fUTI, performing rectal swab–based TPAs in patients undergoing TRUS-PB.
Patient summary: We reviewed infections occurring after transrectal prostate biopsy in over 3000 patients. The use of antibiotics chosen based on a simple rectal swab decreased the rate of postbiopsy fever and urinary tract infections by half compared with the use of standard antibiotics. More research is needed to understand whether this approach also prevents the rare but serious complication of sepsis. en-copyright= kn-copyright= en-aut-name=TsuboiIchiro en-aut-sei=Tsuboi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Kardoust PariziMehdi en-aut-sei=Kardoust Parizi en-aut-mei=Mehdi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=MiszczykMarcin en-aut-sei=Miszczyk en-aut-mei=Marcin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FazekasTamás en-aut-sei=Fazekas en-aut-mei=Tamás kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=CormioAngelo en-aut-sei=Cormio en-aut-mei=Angelo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WadaKoichiro en-aut-sei=Wada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KarakiewiczPierre I. en-aut-sei=Karakiewicz en-aut-mei=Pierre I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ChlostaPiotr en-aut-sei=Chlosta en-aut-mei=Piotr kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=BrigantiAlberto en-aut-sei=Briganti en-aut-mei=Alberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShariatShahrokh F. en-aut-sei=Shariat en-aut-mei=Shahrokh F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=3 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=4 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=5 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=6 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=12 en-affil=Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre kn-affil= affil-num=13 en-affil=Department of Urology, Jagiellonian University Medical College kn-affil= affil-num=14 en-affil=Unit of Urology/Division of Oncology, Gianfranco Soldera Prostate Cancer Lab, IRCCS San Raffaele Scientific Institute kn-affil= affil-num=15 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= en-keyword=Febrile urinary tract infection kn-keyword=Febrile urinary tract infection en-keyword=Targeted prophylactic antibiotics kn-keyword=Targeted prophylactic antibiotics en-keyword=Transrectal prostate biopsy kn-keyword=Transrectal prostate biopsy en-keyword=Sepsis kn-keyword=Sepsis END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=387 end-page=392 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Utility of a Preoperative 3D Imaging Analysis System for Trigonal Meningioma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Trigonal meningiomas are rare and pose surgical challenges due to their deep location and proximity to critical neuroanatomical structures. We present the case of a 67-year-old woman with a growing trigonal meningioma successfully resected with guidance by a preoperative 3D imaging analysis system. Integration of CT and MRI including diffusion tensor imaging (DTI) enabled precise mapping of the optic radiation, guiding a middle temporal gyrus approach. Preoperative embolization reduced tumor vascularity, facilitating gross total resection with minimal blood loss. This case highlights the effectiveness of preoperative 3D imaging systems in optimizing surgical planning and improving outcomes in complex neurosurgical cases. en-copyright= kn-copyright= en-aut-name=MoriYusuke en-aut-sei=Mori en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OmaeRyo en-aut-sei=Omae en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=IshidaJoji en-aut-sei=Ishida en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiiKentaro en-aut-sei=Fujii en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HarumaJun en-aut-sei=Haruma en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiramatsuMasafumi en-aut-sei=Hiramatsu en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsushitaToshi en-aut-sei=Matsushita en-aut-mei=Toshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=trigonal meningioma kn-keyword=trigonal meningioma en-keyword=imaging analysis kn-keyword=imaging analysis en-keyword=diffusion tensor imaging kn-keyword=diffusion tensor imaging END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=369 end-page=379 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Blood Pressure and Heart Rate Patterns Identified by Unsupervised Machine Learning and Their Associations with Subclinical Cerebral and Renal Damage in a Japanese Community: The Masuda Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=We applied unsupervised machine learning to analyze blood pressure (BP) and resting heart rate (HR) patterns measured during a 1-year period to assess their cross-sectional relationships with subclinical cerebral and renal target damage. Dimension reduction via uniform manifold approximation and projection, followed by K-means++ clustering, was used to categorize 362 community-dwelling participants (mean age, 56.2 years; 54.9% women) into three groups: Low BP and Low HR (Lo-BP/Lo-HR), High BP and High HR (Hi-BP/Hi-HR), and Low BP and High HR (Lo-BP/Hi-HR). Cerebral vessel lesions were defined as the presence of at least one of the following magnetic resonance imaging findings: lacunar infarcts, white matter hyperintensities, cerebral microbleeds, or intracranial artery stenosis. A high urinary albumin-to-creatinine ratio (UACR) was defined as the top 10% (≥ 12 mg/g) of the mean value from ≥2 measurements. Poisson regression with robust error variance, adjusted for demographics, lifestyle, and medical history, showed that the Hi-BP/Hi-HR group had relative risks of 3.62 (95% confidence interval, 1.75-7.46) for cerebral vessel lesions and 3.58 (1.33-9.67) for high UACR, and the Lo-BP/Hi-HR group had a relative risk of 3.09 (1.12-8.57) for high UACR, compared with the Lo-BP/Lo-HR group. These findings demonstrate the utility of an unsupervised, data-driven approach for identifying physiological patterns associated with subclinical target organ damage. en-copyright= kn-copyright= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KinutaMinako en-aut-sei=Kinuta en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MunetomoSosuke en-aut-sei=Munetomo en-aut-mei=Sosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukudaMari en-aut-sei=Fukuda en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KojimaKatsuhide en-aut-sei=Kojima en-aut-mei=Katsuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TaniguchiKaori en-aut-sei=Taniguchi en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakahataNoriko en-aut-sei=Nakahata en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KandaHideyuki en-aut-sei=Kanda en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Environmental Medicine and Public Health, Izumo, Shimane University Faculty of Medicine kn-affil= affil-num=7 en-affil=Department of Health and Nutrition, The University of Shimane Faculty of Nursing and Nutrition kn-affil= affil-num=8 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=blood pressure kn-keyword=blood pressure en-keyword=heart rate kn-keyword=heart rate en-keyword=subclinical disease kn-keyword=subclinical disease en-keyword=uniform manifold approximation and projection kn-keyword=uniform manifold approximation and projection en-keyword=unsupervised machine learning kn-keyword=unsupervised machine learning END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=329 end-page=337 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Current Status of Extracorporeal Membrane Oxygenation as a Treatment Strategy for Primary Graft Dysfunction after Lung Transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Primary graft dysfunction (PGD) is one of the major risk factors affecting patients’ short- and long-term survival after lung transplantation. No particular management strategy has been established for PGD; supportive care is the mainstay of PGD treatment. When a supportive strategy fails, the patient may require the introduction of extracorporeal membrane oxygenation (ECMO) as the last-resort measure for severe PGD. A variety of study of ECMO as a PGD treatment was reported and the management of PGD patients developed so far. Early recognition of a patient’s need for ECMO and its prompt initiation are critical to improved outcomes. The use of venovenous-ECMO became the preferred procedure for PGD rather than venoarterial-ECMO. However, the current ECMO strategy has limitations, and using ECMO to manage patients with PGD is not sufficiently effective. Further studies are required to develop this promising technology. en-copyright= kn-copyright= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=lung transplantation kn-keyword=lung transplantation en-keyword=primary graft dysfunction kn-keyword=primary graft dysfunction en-keyword=extracorporeal membrane oxygenation kn-keyword=extracorporeal membrane oxygenation en-keyword=ex vivo lung perfusion kn-keyword=ex vivo lung perfusion END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=321 end-page=328 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 Review of the Endoscopic Treatment for Bile Leak Following Cholecystectomy and Hepatic Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bile leak occurs in 2-25% of liver transplant, 3-27% of hepatic resection, and 0.1-4% of cholecystectomy cases. The clinical course of bile leak varies depending on the type of surgery that caused the fistula, as well as the type, severity, and timing of bile duct injury. Although infections resulting from bile leak can be life-threatening, the introduction of endoscopic treatment has enabled some patients to avoid reoperation and has reduced the negative impact on quality of life associated with external fistulas for percutaneous drainage. Endoscopic interventions, such as sphincterotomy and stent placement, reduce the pressure gradient between the bile duct and duodenum, facilitating bile drainage through the papilla and promoting the closure of the leak. We reviewed the literature from 2004 to 2024 regarding bile leak following cholecystectomy and liver surgery, examining recommended techniques, timing, and treatment outcomes. In cases of bile leak following cholecystectomy, clinical success was achieved in 72-96% of cases, while success rates for bile leak following liver surgery ranged from 50% to 100%. Although endoscopic treatment is effective, it is not universally applicable, and its limitations must be carefully considered. en-copyright= kn-copyright= en-aut-name=ObataTaisuke en-aut-sei=Obata en-aut-mei=Taisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University 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= en-keyword=bile leak kn-keyword=bile leak en-keyword=cholecystectomy kn-keyword=cholecystectomy en-keyword=hepatic surgery kn-keyword=hepatic surgery en-keyword=endoscopic retrograde cholangiography kn-keyword=endoscopic retrograde cholangiography en-keyword=bridging stent placement kn-keyword=bridging stent placement END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=5 article-no= start-page=3933 end-page=3946 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=Topology-Driven Configuration of Emulation Networks With Deterministic Templating en-subtitle= kn-subtitle= en-abstract= kn-abstract=Network emulation is an important component of a digital twin for verifying network behavior without impacting on the service systems. Although we need to repeatedly change network topologies and configuration settings as a part of trial and error for verification, it is not easy to reflect the change without failures because the change affects multiple devices, even if it is as simple as adding a device. We present topology-driven configuration, an idea to separate network topology and generalized configuration to make it easy to change them. Based on this idea, we aim to realize a scalable, simple, and effective configuration platform for emulation networks. We design a configuration generation method using simple and deterministic config templates with a new network parameter data model, and implement it as dot2net. We evaluate three perspectives, scalability, simplicity, and efficacy, of the proposed method using dot2net through measurement and user experiments on existing test network scenarios. en-copyright= kn-copyright= en-aut-name=KobayashiSatoru en-aut-sei=Kobayashi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShiibaRyusei en-aut-sei=Shiiba en-aut-mei=Ryusei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiwaShinsuke en-aut-sei=Miwa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyachiToshiyuki en-aut-sei=Miyachi en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukudaKensuke en-aut-sei=Fukuda en-aut-mei=Kensuke 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=Department of Informatics, School of Multidisciplinary Sciences, The Graduate University of Advanced Studies, Sokendai kn-affil= affil-num=3 en-affil=StarBED Technology Center, Testbed Research, Development and Operations Laboratory, National Institute of Information and Communications Technology kn-affil= affil-num=4 en-affil=Strategic Planning Department, Strategic Planning Office, National Institute of Information and Communications Technology kn-affil= affil-num=5 en-affil=Department of Informatics, School of Multidisciplinary Sciences, The Graduate University of Advanced Studies, Sokendai kn-affil= en-keyword=Configuration management kn-keyword=Configuration management en-keyword=template kn-keyword=template en-keyword=emulation network kn-keyword=emulation network en-keyword=topology graph kn-keyword=topology graph END start-ver=1.4 cd-journal=joma no-vol=55 cd-vols= no-issue=6 article-no= start-page=643 end-page=649 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real-world clinical usage and efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer: a multi-institutional study in the CsJUC en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: To evaluate the real-world clinical usage and effectiveness of apalutamide in men with nonmetastatic castration-resistant prostate cancer (nmCRPC).
Methods: We retrospectively reviewed the data of 186 men who received apalutamide across 17 institutions. The primary outcomes were the clinical usage of apalutamide for nmCRPC: prior usage of other androgen receptor signaling inhibitors (ARSIs), prior radical treatment, and the distribution of the prostate-specific antigen (PSA) doubling time (PSA-DT) at the initial administration of apalutamide. The secondary outcomes were the efficacy of apalutamide: PSA response (50% or 90% decline), progression-free survival, and skin-adverse events (AEs).
Results: We identified 75 patients with nmCRPC. A total of 31 (41.3%) patients received prior treatment with other ARSIs. A total of 42 men (56%) did not receive any prior radical treatment. The PSA-DT was <3.0, 3.0–5.9, 6.0–10, and > 10 months in 34.7%, 40%, 14.7%, and 10.6% of the patients, respectively. Patients receiving prior treatment with other ARSIs showed a significantly lower PSA response (PSA 50% decline, 88.4% vs. 18.8%; PSA 90% decline, 60.5% vs. 6.2%, P < .001, respectively) and significantly shorter progression-free survival (median: 37 months vs. 4 months; log-rank P < .001) than those without prior ARSI treatment, although cancer status did not differ between the groups. Skin-AEs were observed in 42.7%.
Conclusions: This real-world study revealed that apalutamide was used for the treatment after other ARSIs in >40% of patients with nmCRPC and showed limited efficacy in this context, although the effectiveness of apalutamide without prior other ARSI treatment was comparable with that reported in clinical trial results. en-copyright= kn-copyright= en-aut-name=TohiYoichiro en-aut-sei=Tohi en-aut-mei=Yoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiKeita en-aut-sei=Kobayashi en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DaizumotoKei en-aut-sei=Daizumoto en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SekinoYohei en-aut-sei=Sekino en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukuharaHideo en-aut-sei=Fukuhara en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NiigawaHeima en-aut-sei=Niigawa en-aut-mei=Heima kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimizuRyutaro en-aut-sei=Shimizu en-aut-mei=Ryutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakamotoAtsushi en-aut-sei=Takamoto en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=NagamiTaichi en-aut-sei=Nagami en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HayashidaYushi en-aut-sei=Hayashida en-aut-mei=Yushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HiramaHiromi en-aut-sei=Hirama en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShiraishiKoji en-aut-sei=Shiraishi en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TomidaRyotaro en-aut-sei=Tomida en-aut-mei=Ryotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KobatakeKohei en-aut-sei=Kobatake en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=InoueKeiji en-aut-sei=Inoue en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MiyajiYoshiyuki en-aut-sei=Miyaji en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=19 ORCID= en-aut-name=MorizaneShuichi en-aut-sei=Morizane en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MiuraNoriyoshi en-aut-sei=Miura en-aut-mei=Noriyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=WadaKoichiro en-aut-sei=Wada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=SugimotoMikio en-aut-sei=Sugimoto en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=Chu-shikoku Japan Urological Consortium en-aut-sei=Chu-shikoku Japan Urological Consortium en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= affil-num=1 en-affil=Department of Urology, Faculty of Medicine, Kagawa University kn-affil= affil-num=2 en-affil=Department of Urology, Graduate School of Medicine, Yamaguchi University kn-affil= affil-num=3 en-affil=Department of Urology, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=5 en-affil=Department of Urology, Kochi Medical School kn-affil= affil-num=6 en-affil=Department of Urology, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Division of Urology, Department of Surgery, Faculty of Medicine, Tottori University kn-affil= affil-num=9 en-affil=Department of Urology, Fukuyama City Hospital kn-affil= affil-num=10 en-affil=Department of Urology, Ehime University kn-affil= affil-num=11 en-affil=Department of Urology, Shimane University Faculty of Medicine kn-affil= affil-num=12 en-affil=Department of Urology, Sakaide City Hospital kn-affil= affil-num=13 en-affil=Department of Urology, KKR Takamatsu Hospital kn-affil= affil-num=14 en-affil=Department of Urology, Graduate School of Medicine, Yamaguchi University kn-affil= affil-num=15 en-affil=Department of Urology, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=16 en-affil=Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=17 en-affil=Department of Urology, Kochi Medical School kn-affil= affil-num=18 en-affil=Department of Urology, Kawasaki Medical School kn-affil= affil-num=19 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Division of Urology, Department of Surgery, Faculty of Medicine, Tottori University kn-affil= affil-num=21 en-affil=Department of Urology, Ehime University kn-affil= affil-num=22 en-affil=Department of Urology, Shimane University Faculty of Medicine kn-affil= affil-num=23 en-affil=Department of Urology, Faculty of Medicine, Kagawa University kn-affil= affil-num=24 en-affil= kn-affil= en-keyword=apalutamide kn-keyword=apalutamide en-keyword=nonmetastatic castration-resistant prostate cancer kn-keyword=nonmetastatic castration-resistant prostate cancer en-keyword=prostate cancer kn-keyword=prostate cancer en-keyword=prostate-specific antigen response kn-keyword=prostate-specific antigen response en-keyword=PSA-doubling time kn-keyword=PSA-doubling time END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=2 article-no= start-page=1 end-page=13 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Advancements in systemic therapy for muscle-invasive bladder cancer: A systematic review from the beginning to the latest updates en-subtitle= kn-subtitle= en-abstract= kn-abstract=Context: Several phase III randomized controlled trials (RCTs) have shown the importance of perioperative systemic therapy, especially for the efficacy of immune checkpoint inhibitors (ICIs) in both neoadjuvant and adjuvant settings for muscle-invasive bladder cancer (MIBC).
Objective: To synthesize the growing evidence on the efficacy and safety of systemic therapies for MIBC utilizing the data from RCTs.
Evidence acquisition: Three databases and ClinicalTrials.gov were searched in October 2024 for eligible RCTs evaluating oncologic outcomes in MIBC patients treated with systemic therapy. We evaluated pathological complete response (pCR), disease-free survival (DFS), progression-free survival (PFS), event-free survival (EFS), overall survival (OS), and adverse events (AEs).
Evidence synthesis: Thirty-three RCTs (including 14 ongoing trials) were included in this systematic review. Neoadjuvant chemotherapy improved OS compared to radical cystectomy alone. Particularly, the VESPER trial demonstrated that dd-MVAC provided oncological benefits over GC alone in terms of pCR rates, OS (HR: 0.71), and PFS (HR: 0.70). Recently, the NIAGARA trial showed that perioperative durvalumab plus GC outperformed GC alone in terms of pCR rates, OS (HR: 0.75), and EFS (HR: 0.68). Despite the lack of data on overall AE rates in the VESPER trial, differential safety profiles in hematologic toxicity were reported between dd-MVAC and durvalumab plus GC regimens. In the adjuvant setting, no study provided the OS benefit from adjuvant chemotherapy. However, only adjuvant nivolumab had significant DFS and OS benefits compared to placebo.
Conclusions: Neoadjuvant chemotherapy remains the current standard of care for MIBC. Durvalumab shed light on the promising impact of ICIs added to neoadjuvant chemotherapy. Nivolumab is the only ICI recommended as adjuvant therapy in patients who harbored adverse pathologic outcomes. Ongoing trials will provide further information on the impact of combination therapy, including chemotherapy, ICIs, and enfortumab vedotin, in both neoadjuvant and adjuvant settings. en-copyright= kn-copyright= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TeohJeremy Yuen-Chun en-aut-sei=Teoh en-aut-mei=Jeremy Yuen-Chun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriKeiichiro en-aut-sei=Mori en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=RajwaPaweł en-aut-sei=Rajwa en-aut-mei=Paweł kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=QuhalFahad en-aut-sei=Quhal en-aut-mei=Fahad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=PradereBenjamin en-aut-sei=Pradere en-aut-mei=Benjamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MoschiniMarco en-aut-sei=Moschini en-aut-mei=Marco kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShariatShahrokh F. en-aut-sei=Shariat en-aut-mei=Shahrokh F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MikiJun en-aut-sei=Miki en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KimuraTakahiro en-aut-sei=Kimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=3 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=4 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=8 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=9 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=10 en-affil=Department of Urology, San Raffaele Hospital and Scientific Institute kn-affil= affil-num=11 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=12 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=13 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= en-keyword=immune checkpoint inhibitors kn-keyword=immune checkpoint inhibitors en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=urothelial carcinoma kn-keyword=urothelial carcinoma en-keyword=muscle-invasive kn-keyword=muscle-invasive en-keyword=neoadjuvant kn-keyword=neoadjuvant en-keyword=adjuvant kn-keyword=adjuvant END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=22 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250105 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relay Node Selection Methods for UAV Navigation Route Constructions in Wireless Multi-Hop Network Using Smart Meter Devices en-subtitle= kn-subtitle= en-abstract= kn-abstract=Unmanned aerial vehicles (UAVs) offer solutions to issues like traffic congestion and labor shortages. We developed a distributed UAV management system inspired by virtual circuit and datagram methods in packet-switching networks. By installing houses with wireless terminals, UAVs navigate routes in a multi-hop network, communicating with ground nodes. UAVs are treated as network packets, ground devices are treated as routers, and their connections are treated as links. Activating all nodes as relays increases control message traffic and node load. To optimize connectivity, we minimize relay nodes, connecting non-relay nodes to the nearest relay. This study proposes four relay node selection methods: random selection, two adjacency-based methods, and our innovative approach using Multipoint Relay (MPR) from the Optimized Link State Routing Protocol (OLSR). We evaluated these methods according to their route construction success rates, relay node counts, route lengths, and so on. The MPR-based method proved most effective for UAV route construction. However, fewer relay nodes increase link collisions, and we identify the minimum relay density needed to balance efficiency and conflict reduction. en-copyright= kn-copyright= en-aut-name=OhkawaShuto en-aut-sei=Ohkawa en-aut-mei=Shuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UedaKiyoshi en-aut-sei=Ueda en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyoshiTakumi en-aut-sei=Miyoshi en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamazakiTaku en-aut-sei=Yamazaki en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoRyo en-aut-sei=Yamamoto en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FunabikiNobuo en-aut-sei=Funabiki en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Engineering, Nihon University kn-affil= affil-num=2 en-affil=Graduate School of Engineering, Nihon University kn-affil= affil-num=3 en-affil=College of Systems Engineering and Science, Shibaura Institute of Technology kn-affil= affil-num=4 en-affil=College of Systems Engineering and Science, Shibaura Institute of Technology kn-affil= affil-num=5 en-affil=Graduate School of Informatics and Engineering, The University of Electro-Communications kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=network of wireless devices kn-keyword=network of wireless devices en-keyword=UAV delivery kn-keyword=UAV delivery en-keyword=ad hoc network kn-keyword=ad hoc network END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=3 article-no= start-page=52 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250908 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An Extension of Input Setup Assistance Service Using Generative AI to Unlearned Sensors for the SEMAR IoT Application Server Platform en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nowadays, Internet of Things (IoT) application systems are broadly applied to various sectors of society for efficient management by monitoring environments using sensors, analyzing sampled data, and giving proper feedback. For their fast deployment, we have developed Smart Environmental Monitoring and Analysis in Real Time (SEMAR) as an integrated IoT application server platform and implemented the input setup assistance service using prompt engineering and a generative AI model to assist connecting sensors to SEMAR with step-by-step guidance. However, the current service cannot assist in connections of the sensors not learned by the AI model, such as newly released ones. To address this issue, in this paper, we propose an extension to the service for handling unlearned sensors by utilizing datasheets with four steps: (1) users input a PDF datasheet containing information about the sensor, (2) key specifications are extracted from the datasheet and structured into markdown format using a generative AI, (3) this data is saved to a vector database using chunking and embedding methods, and (4) the data is used in Retrieval-Augmented Generation (RAG) to provide additional context when guiding users through sensor setup. Our evaluation with five generative AI models shows that OpenAI’s GPT-4o achieves the highest accuracy in extracting specifications from PDF datasheets and the best answer relevancy (0.987), while Gemini 2.0 Flash delivers the most balanced results, with the highest overall RAGAs score (0.76). Other models produced competitive but mixed outcomes, averaging 0.74 across metrics. The step-by-step guidance function achieved a task success rate above 80%. In a course evaluation by 48 students, the system improved the student test scores, further confirming the effectiveness of our proposed extension. en-copyright= kn-copyright= 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=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=PandumanYohanes Yohanie Fridelin en-aut-sei=Panduman en-aut-mei=Yohanes Yohanie Fridelin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=PradhanaAnak Agung Surya en-aut-sei=Pradhana en-aut-mei=Anak Agung Surya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Noprianto en-aut-sei=Noprianto en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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 Information Science and Technology, The University of Osaka kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=Internet of Things kn-keyword=Internet of Things en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=Retrieval-Augmented Generation kn-keyword=Retrieval-Augmented Generation en-keyword=review kn-keyword=review en-keyword=application server platform kn-keyword=application server platform en-keyword=SEMAR kn-keyword=SEMAR en-keyword=sensor input kn-keyword=sensor input END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=7 article-no= start-page=607 end-page= 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=A Fundamental Statistics Self-Learning Method with Python Programming for Data Science Implementations en-subtitle= kn-subtitle= en-abstract= kn-abstract=The increasing demand for data-driven decision making to maintain the innovations and competitiveness of organizations highlights the need for data science educations across academia and industry. At its core is a solid understanding of statistics, which is necessary for conducting a thorough analysis of data and deriving valuable insights. Unfortunately, conventional statistics learning often lacks practice in real-world applications using computer programs, causing a separation between conceptual knowledge of statistics equations and their hands-on skills. Integrating statistics learning into Python programming can convey an effective solution for this problem, where it has become essential in data science implementations, with extensive and versatile libraries. In this paper, we present a self-learning method for fundamental statistics through Python programming for data science studies. Unlike conventional approaches, our method integrates three types of interactive problems—element fill-in-blank problem (EFP), grammar-concept understanding problem (GUP), and value trace problem (VTP)—in the Programming Learning Assistant System (PLAS). This combination allows students to write code, understand concepts, and trace the output value while obtaining instant feedback so that they can improve retention, knowledge, and practical skills in learning statistics using Python programming. For evaluations, we generated 22 instances using source codes for fundamental statistics topics, and assigned them to 40 first-year undergraduate students at UPN Veteran Jawa Timur, Indonesia. Statistics analytical methods were utilized to analyze the student learning performances. The results show that a significant correlation (𝜌<0.05) exists between the students who solved our proposal and those who did not. The results confirm that it can effectively assist students in learning fundamental statistics self-learning using Python programming for data science implementations. en-copyright= kn-copyright= en-aut-name=RiyantokoPrismahardi Aji en-aut-sei=Riyantoko en-aut-mei=Prismahardi Aji 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=BrataKomang Candra en-aut-sei=Brata en-aut-mei=Komang Candra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=DamalianaAviolla Terza en-aut-sei=Damaliana en-aut-mei=Aviolla Terza kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=PrasetyaDwi Arman en-aut-sei=Prasetya en-aut-mei=Dwi Arman 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 Data Science, Universitas Pembangunan Nasional Veteran Jawa Timur kn-affil= affil-num=6 en-affil=Department of Data Science, Universitas Pembangunan Nasional Veteran Jawa Timur kn-affil= en-keyword=fundamental statistics kn-keyword=fundamental statistics en-keyword=self-learning method kn-keyword=self-learning method en-keyword=Python programming kn-keyword=Python programming en-keyword=data science kn-keyword=data science END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=7 article-no= start-page=588 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250708 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Map Information Collection Tool for a Pedestrian Navigation System Using Smartphone en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nowadays, a pedestrian navigation system using a smartphone has become popular as a useful tool to reach an unknown destination. When the destination is the office of a person, a detailed map information is necessary on the target area such as the room number and location inside the building. The information can be collected from various sources including Google maps, websites for the building, and images of signs. In this paper, we propose a map information collection tool for a pedestrian navigation system. To improve the accuracy and completeness of information, it works with the four steps: (1) a user captures building and room images manually, (2) an OCR software using Google ML Kit v2 processes them to extract the sign information from images, (3) web scraping using Scrapy (v2.11.0) and crawling with Apache Nutch (v1.19) software collects additional details such as room numbers, facilities, and occupants from relevant websites, and (4) the collected data is stored in the database to be integrated with a pedestrian navigation system. For evaluations of the proposed tool, the map information was collected for 10 buildings at Okayama University, Japan, a representative environment combining complex indoor layouts (e.g., interconnected corridors, multi-floor facilities) and high pedestrian traffic, which are critical for testing real-world navigation challenges. The collected data is assessed in completeness and effectiveness. A university campus was selected as it presents a complex indoor and outdoor environment that can be ideal for testing pedestrian navigations in real-world scenarios. With the obtained map information, 10 users used the navigation system to successfully reach destinations. The System Usability Scale (SUS) results through a questionnaire confirms the high usability. en-copyright= kn-copyright= en-aut-name=BatubulanKadek Suarjuna en-aut-sei=Batubulan en-aut-mei=Kadek Suarjuna 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=BrataKomang Candra en-aut-sei=Brata en-aut-mei=Komang Candra 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=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=5 ORCID= en-aut-name=HidayatiShintami Chusnul en-aut-sei=Hidayati en-aut-mei=Shintami Chusnul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Department of Informatics, Institut Teknologi Sepuluh Nopember kn-affil= en-keyword=pedestrian navigation kn-keyword=pedestrian navigation en-keyword=map information kn-keyword=map information en-keyword=optical character recognition (OCR) kn-keyword=optical character recognition (OCR) en-keyword=smartphones kn-keyword=smartphones en-keyword=web scraping kn-keyword=web scraping en-keyword=system usability scale (SUS) kn-keyword=system usability scale (SUS) END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=5 article-no= start-page=195 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250428 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An Improved Reference Paper Collection System Using Web Scraping with Three Enhancements en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nowadays, accessibility to academic papers has been significantly improved with electric publications on the internet, where open access has become common. At the same time, it has increased workloads in literature surveys for researchers who usually manually download PDF files and check their contents. To solve this drawback, we have proposed a reference paper collection system using a web scraping technology and natural language models. However, our previous system often finds a limited number of relevant reference papers after taking long time, since it relies on one paper search website and runs on a single thread at a multi-core CPU. In this paper, we present an improved reference paper collection system with three enhancements to solve them: (1) integrating the APIs from multiple paper search web sites, namely, the bulk search endpoint in the Semantic Scholar API, the article search endpoint in the DOAJ API, and the search and fetch endpoint in the PubMed API to retrieve article metadata, (2) running the program on multiple threads for multi-core CPU, and (3) implementing Dynamic URL Redirection, Regex-based URL Parsing, and HTML Scraping with URL Extraction for fast checking of PDF file accessibility, along with sentence embedding to assess relevance based on semantic similarity. For evaluations, we compare the number of obtained reference papers and the response time between the proposal, our previous work, and common literature search tools in five reference paper queries. The results show that the proposal increases the number of relevant reference papers by 64.38% and reduces the time by 59.78% on average compared to our previous work, while outperforming common literature search tools in reference papers. Thus, the effectiveness of the proposed system has been demonstrated in our experiments. en-copyright= kn-copyright= en-aut-name=FahrudinTresna Maulana en-aut-sei=Fahrudin en-aut-mei=Tresna Maulana 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=BrataKomang Candra en-aut-sei=Brata en-aut-mei=Komang Candra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaingInzali en-aut-sei=Naing en-aut-mei=Inzali kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=MuhaiminAmri en-aut-sei=Muhaimin en-aut-mei=Amri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=PrasetyaDwi Arman en-aut-sei=Prasetya en-aut-mei=Dwi Arman kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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 Data Science, Universitas Pembangunan Nasional Veteran Jawa Timur kn-affil= affil-num=7 en-affil=Department of Data Science, Universitas Pembangunan Nasional Veteran Jawa Timur kn-affil= en-keyword=reference paper collection kn-keyword=reference paper collection en-keyword=multiple API integration kn-keyword=multiple API integration en-keyword=PDF accessibility kn-keyword=PDF accessibility en-keyword=open access kn-keyword=open access en-keyword=multiple threads kn-keyword=multiple threads END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue= article-no= start-page=1646835 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251008 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Muscle morphological adaptations to resistance training and sports participation in children and adolescents: a scoping review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: This scoping review aimed to systematically map the existing literature on the effects of resistance training (RT) and sports participation on muscle morphology in children and adolescents.
Methods: Herein, a literature search was conducted using three electronic databases: PubMed, Scopus, and Web of Science. The inclusion criteria were as follows: articles that were written in English, which used chronic RT or a combination of RT with other training methods, or investigated the effects of sports participation, and reported muscle morphology as an outcome.
Results: This scoping review included 29 studies: 17 cross-sectional studies, 3 prospective observational studies, and 9 interventional studies. The following distribution was obtained after categorizing the included studies according to participant age: aged 6–11 years, 12 articles; aged 12–14 years, 10 articles; and aged 15–17 years, 10 articles. The designs of interventional studies included eight quasi-experimental parallel-group trials and a quasi-experimental crossover trial. However, none of the included interventional studies followed the CONSORT guidelines for conducting randomized controlled trials. Across the included studies, 14 different sports were analyzed for their effects on muscle morphology. Four studies combined players from various sports. In the included studies, 47 different muscles or muscle groups were examined. Our results identified unexplored muscles because our included studies did not examine the volume of lower leg muscles.
Conclusion: Future research directions in this field, including experimental design and targeted muscles, are warranted. en-copyright= kn-copyright= en-aut-name=EnomotoShota en-aut-sei=Enomoto en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TottoriNobuaki en-aut-sei=Tottori en-aut-mei=Nobuaki 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=Graduate School of Education, Hyogo University of Teacher Education kn-affil= en-keyword=athlete kn-keyword=athlete en-keyword=cross-sectional area kn-keyword=cross-sectional area en-keyword=muscle thickness kn-keyword=muscle thickness en-keyword=muscle volume kn-keyword=muscle volume en-keyword=muscle-strengthening activity kn-keyword=muscle-strengthening activity en-keyword=youth kn-keyword=youth END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=34964 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251007 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Periodontitis associated with Porphyromonas gingivalis infection is a risk factor for infertility through uterine hypertrophy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Periodontitis has recently been recognized as a potential risk factor for infertility due to its adverse effect on conception, although the underlying mechanisms remain unclear. This study investigated serum IgG antibody titers against periodontopathogenic bacteria in women with unexplained infertility and investigated how periodontal inflammation affects pregnancy and uterine function using a ligature-induced periodontitis mouse model infected with Porphyromonas gingivalis (Pg). IgG antibody titers against seven periodontopathogenic bacteria strains were measured by ELISA in 76 spontaneously pregnant women and 70 women undergoing infertility treatment. In the in vivo study, periodontitis mice were bred four weeks after periodontitis induction. Birth numbers, newborn weights, and gestation periods were assessed. To evaluate periodontal inflammation, alveolar bone, serum, and uterus was collected before mating. Uterine tissue was evaluated through histological and immunohistochemical staining. Women receiving infertility treatment were significantly older and had higher IgG titers against three Pg strains. Periodontitis mice had fewer births, lower newborn weights, and increased uterine cross-sectional areas. Additionally, elevated estrogen receptor α and progesterone receptor expression levels were observed in endometrial and stromal tissues. These results suggest that periodontitis may cause uterine hypertrophy and hormone receptor changes, potentially impairing pregnancy. en-copyright= kn-copyright= en-aut-name=Kamei-NagataChiaki en-aut-sei=Kamei-Nagata en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakoHidefumi en-aut-sei=Sako en-aut-mei=Hidefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakaidaKyosuke en-aut-sei=Sakaida en-aut-mei=Kyosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakayamaMasa-aki en-aut-sei=Nakayama en-aut-mei=Masa-aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MandaiHiroki en-aut-sei=Mandai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Kubota-TakamoriMoyuka en-aut-sei=Kubota-Takamori en-aut-mei=Moyuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KiyamaFumiko en-aut-sei=Kiyama en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HiraiKimito en-aut-sei=Hirai en-aut-mei=Kimito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IkedaAtsushi en-aut-sei=Ikeda en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Takeuchi-HatanakaKazu en-aut-sei=Takeuchi-Hatanaka en-aut-mei=Kazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=Tai-TokuzenMasako en-aut-sei=Tai-Tokuzen en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SakamotoAi en-aut-sei=Sakamoto en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KiyokawaMachiko en-aut-sei=Kiyokawa en-aut-mei=Machiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YamanishiTomomi en-aut-sei=Yamanishi en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OdaTakashi en-aut-sei=Oda en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TakigawaMasayuki en-aut-sei=Takigawa en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MiyakeTakahito en-aut-sei=Miyake en-aut-mei=Takahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science kn-affil= affil-num=8 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=16 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=17 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=18 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=19 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=20 en-affil=Miyake Hello Dental Clinic, Pediatric Dentistry and Orthodontics kn-affil= affil-num=21 en-affil=The Center for Graduate Medical Education (Dental Division), Okayama University Hospital kn-affil= affil-num=22 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=23 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Infertility kn-keyword=Infertility en-keyword=Periodontitis kn-keyword=Periodontitis en-keyword=Porphyromonas gingivalis kn-keyword=Porphyromonas gingivalis en-keyword=Chronic inflammation kn-keyword=Chronic inflammation en-keyword=Uterus kn-keyword=Uterus en-keyword=Sex hormone receptor kn-keyword=Sex hormone receptor END start-ver=1.4 cd-journal=joma no-vol=105 cd-vols= no-issue=4 article-no= start-page=1157 end-page=1167 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of environmental conditions on seed germination and seedling growth in Cuscuta campestris en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dodder (Cuscuta) is an obligate parasitic plant that cannot survive without a host and causes significant damage to crop yields. To understand its growth characteristics before parasitism, we examined the effects of environmental conditions on seed germination and seedling growth in Cuscuta campestris Yunck. Among various factors, we focused on the effects of light, pH, temperature, sugars, salts, hormones, amino acids and polyamines on seeds sown on agar plates. Regarding the effect of light on germination, far-red light was preferable rather than red light and the reversible response of seeds to red and far-red light was confirmed, implicating a phytochrome-mediated signaling pathway opposite to that in many seed plants. Among the amino acids, aspartic acid and alanine had a promotive effect, while histidine had an inhibitory effect on germination. We further found that, in addition to gibberellic acid, methyl jasmonate stimulated both germination and shoot elongation. While 2,4-D extended the viability of trichomes around the root cap, kinetin induced the formation of scale leaves on the shoot and undifferentiated cell clusters at the base of the shoot and root tip. Real-time reverse transcriptase PCR (RT-PCR) experiments confirmed that the expression of a putative RbcS gene for photosynthesis showed no response to light, whereas that of a Phytochrome A homolog increased in the dark. Our results indicate that some of the molecular mechanisms involved in responding to light and hormone signals are uniquely modified in dodder seedlings, providing clues for understanding the survival strategy of parasitic plants. en-copyright= kn-copyright= en-aut-name=NagaoKoki en-aut-sei=Nagao en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiTaku en-aut-sei=Takahashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YokoyamaRyusuke en-aut-sei=Yokoyama en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= en-keyword=Cuscuta kn-keyword=Cuscuta en-keyword=Environmental conditions kn-keyword=Environmental conditions en-keyword=Germination kn-keyword=Germination en-keyword=Hormone responses kn-keyword=Hormone responses en-keyword=Seedling growth kn-keyword=Seedling growth END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=4 article-no= start-page=51 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250930 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cancer-associated fibroblast-derived SOD3 enhances lymphangiogenesis to drive metastasis in lung adenocarcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Despite advancements in diagnostic and therapeutic strategies, lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality due to its aggressive metastatic potential. Extracellular superoxide dismutase (SOD3) is an antioxidant enzyme that regulates oxidative stress and is regarded as a tumor suppressor. However, studies have demonstrated that SOD3 can either promote or inhibit cell proliferation and survival in various cancers, and its molecular mechanisms within the tumor microenvironment are poorly understood. In this study, we report a breakthrough in uncovering the role of SOD3 derived from cancer-associated fibroblasts (CAFs) in LUAD. Using LUAD xenograft models co-implanted with SOD3-overexpressing CAFs (CAFSOD3), we observe an aggressive tumor phenotype characterized by increased lymphangiogenesis and lymphatic vessel invasion (LVI) of the tumor. Additionally, LUAD patients with elevated SOD3 levels exhibit a higher incidence of LVI and metastasis. Notably, RNA sequencing of CAFSOD3 reveals that SOD3-mediated VEGF-dependent tumor progression and lymphangiogenesis are up-regulated. Furthermore, single-cell transcriptomic analysis of LUAD clinical samples confirms a strong correlation between SOD3 expression in fibroblasts and characteristics of tumor exacerbation, such as lymphangiogenesis and metastasis. These findings underscore new insights into the role of CAF-derived SOD3 in LUAD progression and highlight its potential as a biomarker and therapeutic target. en-copyright= kn-copyright= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HikitaTakao en-aut-sei=Hikita en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MashimaTomoha en-aut-sei=Mashima en-aut-mei=Tomoha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TorigataKosuke en-aut-sei=Torigata en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ThuYin Min en-aut-sei=Thu en-aut-mei=Yin Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HabuTomohiro en-aut-sei=Habu en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ItoSachio en-aut-sei=Ito en-aut-mei=Sachio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakayamaMasanori en-aut-sei=Nakayama en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=School of Medicine, Kobe University kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Thoracic Surgery, National Hospital Organization, Shikoku Cancer Center kn-affil= affil-num=13 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Cancer-associated fibroblast kn-keyword=Cancer-associated fibroblast en-keyword=Superoxide dismutase 3 kn-keyword=Superoxide dismutase 3 en-keyword=Lymphangiogenesis kn-keyword=Lymphangiogenesis en-keyword=Angiogenesis kn-keyword=Angiogenesis en-keyword=Metastasis kn-keyword=Metastasis en-keyword=Lung adenocarcinoma kn-keyword=Lung adenocarcinoma END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=5 article-no= start-page=650 end-page=661 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development and validation of an algorithm for identifying patients undergoing dialysis from patients with advanced chronic kidney disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Identifying patients on dialysis among those with an estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2 remains challenging. To facilitate clinical research in advanced chronic kidney disease (CKD) using electronic health records, we aimed to develop algorithms to identify dialysis patients using laboratory data obtained in routine practice.
Methods We collected clinical data of patients with an eGFR < 15 mL/min/1.73 m2 from six clinical research core hospitals across Japan: four hospitals for the derivation cohort and two for the validation cohort. The candidate factors for the classification models were identified using logistic regression with stepwise backward selection. To ensure transplant patients were not included in the non-dialysis population, we excluded individuals with the disease code Z94.0.
Results We collected data from 1142 patients, with 640 (56%) currently undergoing hemodialysis or peritoneal dialysis (PD), including 426 of 763 patients in the derivation cohort and 214 of 379 patients in the validation cohort. The prescription of PD solutions perfectly identified patients undergoing dialysis. After excluding patients prescribed PD solutions, seven laboratory parameters were included in the algorithm. The areas under the receiver operation characteristic curve were 0.95 and 0.98 and the positive and negative predictive values were 90.9% and 91.4% in the derivation cohort and 96.2% and 94.6% in the validation cohort, respectively. The calibrations were almost linear.
Conclusions We identified patients on dialysis among those with an eGFR < 15 ml/min/1.73 m2. This study paves the way for database research in nephrology, especially for patients with non-dialysis-dependent advanced CKD. en-copyright= kn-copyright= en-aut-name=ImaizumiTakahiro en-aut-sei=Imaizumi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokotaTakashi en-aut-sei=Yokota en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FunakoshiKouta en-aut-sei=Funakoshi en-aut-mei=Kouta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YasudaKazushi en-aut-sei=Yasuda en-aut-mei=Kazushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HattoriAkiko en-aut-sei=Hattori en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorohashiAkemi en-aut-sei=Morohashi en-aut-mei=Akemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KusakabeTatsumi en-aut-sei=Kusakabe en-aut-mei=Tatsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShojimaMasumi en-aut-sei=Shojima en-aut-mei=Masumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagamineSayoko en-aut-sei=Nagamine en-aut-mei=Sayoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakanoToshiaki en-aut-sei=Nakano en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HuangYong en-aut-sei=Huang en-aut-mei=Yong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MorinagaHiroshi en-aut-sei=Morinaga en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OhtaMiki en-aut-sei=Ohta en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NagashimaSatomi en-aut-sei=Nagashima en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=InoueRyusuke en-aut-sei=Inoue en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NakamuraNaoki en-aut-sei=Nakamura en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OtaHideki en-aut-sei=Ota en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MaruyamaTatsuya en-aut-sei=Maruyama en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=GobaraHideo en-aut-sei=Gobara en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=EndohAkira en-aut-sei=Endoh en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=AndoMasahiko en-aut-sei=Ando en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ShiratoriYoshimune en-aut-sei=Shiratori en-aut-mei=Yoshimune kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MaruyamaShoichi en-aut-sei=Maruyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Nephrology, Nagoya University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital kn-affil= affil-num=3 en-affil=Kyusyu University Hospital kn-affil= affil-num=4 en-affil=Department of Nephrology, Nagoya University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Nephrology, Nagoya University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Advanced Medicine, Nagoya University Hospital kn-affil= affil-num=7 en-affil=Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital kn-affil= affil-num=8 en-affil=Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=9 en-affil=Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=10 en-affil=Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=11 en-affil=Division of Medical Informatics, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Comprehensive Therapy for Chronic Kidney Disease, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Clinical Research Promotion Center, The University of Tokyo Hospital kn-affil= affil-num=14 en-affil=Department of Healthcare Information Management, The University of Tokyo Hospital kn-affil= affil-num=15 en-affil=Medical Information Technology Center, Tohoku University Hospital kn-affil= affil-num=16 en-affil=Medical Information Technology Center, Tohoku University Hospital kn-affil= affil-num=17 en-affil=Medical Information Technology Center, Tohoku University Hospital kn-affil= affil-num=18 en-affil=Clinical Research Promotion Center, The University of Tokyo Hospital kn-affil= affil-num=19 en-affil=Division of Medical Informatics, Okayama University Hospital kn-affil= affil-num=20 en-affil=Department of Medical Informatics, Hokkaido University Hospital kn-affil= affil-num=21 en-affil=Department of Nephrology, Nagoya University Graduate School of Medicine kn-affil= affil-num=22 en-affil=Medical IT Center, Nagoya University Hospital kn-affil= affil-num=23 en-affil=Department of Nephrology, Nagoya University Graduate School of Medicine kn-affil= en-keyword=Chronic kidney disease kn-keyword=Chronic kidney disease en-keyword=Algorithm kn-keyword=Algorithm en-keyword=Classification kn-keyword=Classification en-keyword=Dialysis kn-keyword=Dialysis END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=3 article-no= start-page=335 end-page=349 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=Adaptive strategies and community engagement for sustainable conservation and tourism in Komodo National Park, Indonesia en-subtitle= kn-subtitle= en-abstract= kn-abstract=The sustainability of Komodo protection efforts is closely linked to tourism development. To achieve this, it is important to have a deep understanding of local community behaviors and adaptation strategies. This study focuses on the complex relationships between sociodemographic factors, attitudes towards forest conservation, participation in adaptive management programs, and willingness of local communities in the Komodo district to engage in sustainable tourism practices. Using structural equation modeling (SEM), we analyze the connections that either support or hinder the conservation of Komodo habitats while promoting responsible tourism growth. The results show that sociodemographic characteristics have a significant impact on conservation attitudes, leading to increased participation in adaptive programs that are crucial for sustainable tourism. Additionally, the willingness to adapt is a key factor that influences the level of community involvement in sustainable tourism initiatives. This study emphasizes the importance of developing behavioral and adaptive forest protection programs that cater to both Komodo conservation and the sustainable growth of tourism. Policy recommendations focus on community-centered conservation strategies, education on sustainable practices, and the implementation of adaptive management to ensure the long-term viability of Komodo habitats. Overall, this research provides a nuanced understanding of conservation behavior in regions with rich biodiversity. It highlights the pivotal role of community engagement and adaptive strategies in achieving sustainable tourism and conservation goals. en-copyright= kn-copyright= en-aut-name=SianiparImelda Masni Juniaty en-aut-sei=Sianipar en-aut-mei=Imelda Masni Juniaty kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LeeChun-Hung en-aut-sei=Lee en-aut-mei=Chun-Hung kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimDoo-Chul en-aut-sei=Kim en-aut-mei=Doo-Chul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuryawanI Wayan Koko en-aut-sei=Suryawan en-aut-mei=I Wayan Koko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of International Relations, Faculty of Social and Political Sciences, Universitas Kristen Indonesia kn-affil= affil-num=2 en-affil=Center for Environmental Solution (CVISION), Universitas Pertamina kn-affil= affil-num=3 en-affil=Faculty of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Environmental Engineering, Faculty of Infrastructure Planning, Universitas Pertamina kn-affil= en-keyword=Komodo conservation kn-keyword=Komodo conservation en-keyword=sustainable tourism kn-keyword=sustainable tourism en-keyword=forest protection kn-keyword=forest protection en-keyword=adaptive management programs kn-keyword=adaptive management programs en-keyword=sociodemographic influence kn-keyword=sociodemographic influence END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=9 article-no= start-page=4815 end-page=4837 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=Spatiotemporal evolution of ecosystem carbon storage under land use/land cover dynamics in the coastal region of Central Vietnam en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ecosystem carbon storage is a cost-effective strategy for global climate change mitigation, and its fluctuation is markedly shaped by land use/land cover (LULC) dynamics. Taking Danang city as an example of Central Coastal Vietnam, this study aims to assess LULC changes and analyze the spatiotemporal evolution of carbon storage from 2023 to 2050 under four LULC change scenarios, including natural trend scenario (NTS), ecological protection scenario (EPS), economic development scenario (EDS), and cropland protection scenario (CPS), by integrating the support vector machine-cellular automata-Markov (SVM-CA-Markov) model and the InVEST model. The Optimal Parameters-based Geographical Detector (OPGD) model was subsequently employed to elucidate the impacts of driving factors on the spatial distribution of carbon storage. The results showed that, from 2007 to 2023, Danang city experienced a dramatic back-and-forth transformation between LULC types, with the predominant transitions being from natural forest to acacia tree-dominated plantation forest (6492.31 ha), and from cropland to settlements, acacia tree-dominated plantation forest, and other land (5483.05 ha, 3763.66 ha, 2762.35 ha, respectively). Between 2023 and 2050, LULC transformations in Danang city are projected to yield varying degrees of carbon storage levels across different scenarios. Specifically, carbon storage is anticipated to dwindle by 0.221 Mt, 0.223 Mt, and 0.298 Mt under NTS, EDS, and CPS, respectively, while enhancing by 0.141 Mt under EPS. Regarding the spatial distribution of carbon storage, high values will be chiefly found in the western high-elevation mountainous region, while low values will be concentrated mostly in the eastern lower-lying areas of the city. Additionally, elevation and temperature acted as the two most significant driving factors influencing the spatial distribution of carbon storage, with Q values of 0.88 and 0.86 (p-value < 0.05), respectively. For interaction detection, the combination of elevation and soil exhibited a synergistic reinforcement effect on the spatial partitioning of carbon storage, with a high Q value of 0.9566 (p-value < 0.05). Our study highlights the necessity of ecological conservation measures in Danang city in the on-track pursuit of national net-zero carbon emissions by 2050. en-copyright= kn-copyright= en-aut-name=HoViet Hoang en-aut-sei=Ho en-aut-mei=Viet Hoang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoritaHidenori en-aut-sei=Morita en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HoThanh Ha en-aut-sei=Ho en-aut-mei=Thanh Ha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BachoferFelix en-aut-sei=Bachofer en-aut-mei=Felix kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=University of Agriculture and Forestry, Hue University kn-affil= affil-num=4 en-affil=German Aerospace Center (DLR), Earth Observation Center kn-affil= en-keyword=Carbon sequestration kn-keyword=Carbon sequestration en-keyword=Scenario-based modeling kn-keyword=Scenario-based modeling en-keyword=Remote sensing kn-keyword=Remote sensing en-keyword=Spatial autocorrelation analysis kn-keyword=Spatial autocorrelation analysis END start-ver=1.4 cd-journal=joma no-vol=1019 cd-vols= no-issue= article-no= start-page=A22 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250918 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Experimental and numerical study on the inertial migration of hydrogel particles suspended in square channel flows en-subtitle= kn-subtitle= en-abstract= kn-abstract=The inertial migration of hydrogel particles suspended in a Newtonian fluid flowing through a square channel is studied both experimentally and numerically. Experimental results demonstrate significant differences in the focusing positions of the deformable and rigid particles, highlighting the role of particle deformability in inertial migration. At low Reynolds numbers (Re), hydrogel particles migrate towards the centre of the channel cross-section, whereas the rigid spheres exhibit negligible lateral motion. At finite Re, they focus at four points along the diagonals in the downstream cross-section, in contrast to the rigid particles which focus near the centre of the channel face at similar Re . Numerical simulations using viscous hyperelastic particles as a model for hydrogel particles reproduced the experimental results for the particle distribution with an appropriate Young’s modulus of the hyperelastic particles. Further numerical simulations over a broader range of Re and the capillary number (Ca) reveal various focusing patterns of the particles in the channel cross-section. The phase transitions between them are discussed in terms of the inertial lift and the lift due to particle deformation, which would act in the direction towards lower shear. The stability of the channel centre is analysed using an asymptotic expansion approach to the migration force at low Re and Ca. The theoretical analysis predicts the critical condition for the transition, which is consistent with the direct numerical simulation. These experimental, numerical and theoretical results contribute to a deeper understanding of inertial migration of deformable particles. en-copyright= kn-copyright= en-aut-name=HirohataYuma en-aut-sei=Hirohata en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaiKazusa en-aut-sei=Sai en-aut-mei=Kazusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TangeYuki en-aut-sei=Tange en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishiyamaTomohiro en-aut-sei=Nishiyama en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MinatoHaruka en-aut-sei=Minato en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiDaisuke en-aut-sei=Suzuki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ItanoTomoaki en-aut-sei=Itano en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiyamaKazuyasu en-aut-sei=Sugiyama en-aut-mei=Kazuyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Sugihara-SekiMasako en-aut-sei=Sugihara-Seki en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Engineering Science, The University of Osaka kn-affil= affil-num=2 en-affil=Department of Pure and Applied Physics, Kansai University kn-affil= affil-num=3 en-affil=Department of Pure and Applied Physics, Kansai University kn-affil= affil-num=4 en-affil=Department of Pure and Applied Physics, Kansai 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=Department of Pure and Applied Physics, Kansai University kn-affil= affil-num=8 en-affil=Graduate School of Engineering Science, The University of Osaka kn-affil= affil-num=9 en-affil=Department of Pure and Applied Physics, Kansai University kn-affil= en-keyword=flow-structure interactions kn-keyword=flow-structure interactions en-keyword=microfluidics kn-keyword=microfluidics en-keyword=particle/fluid flow kn-keyword=particle/fluid flow END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=519 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250926 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Specific induction of right ventricular-like cardiomyocytes from human pluripotent stem cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Applications employing human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) require well-characterized, chamber-specific hPSC-CMs. Distinct first heart field (FHF) and second heart field (SHF) cardiac progenitor populations give rise to the left ventricular (LV) and right ventricular (RV) cardiomyocytes, respectively. This developmental difference in cardiomyocyte origin suggests that chamber-specific cardiomyocytes have unique characteristics. Therefore, efficient strategies to differentiate human pluripotent stem cells (hPSCs) specifically to LV-like or RV-like cardiomyocytes are needed and it is still unknown whether there is a phenotypic difference between LV-like cardiomyocytes and RV-like cardiomyocytes derived from hPSCs.
Methods An established hPSC cardiac differentiation protocol employing sequential GSK3β inhibition followed by Wnt inhibition (GiWi) was modified by addition of insulin or BMP antagonists during mesoderm formation. Cardiac progenitor populations were evaluated for FHF and SHF markers, and differentiated hPSC-CMs were characterized for chamber-specific markers.
Results The GiWi protocol produced mainly FHF-like progenitor cells that gave rise to LV-like cardiomyocytes. Inhibition of endogenous BMP signaling during mesoderm induction using insulin or BMP antagonists reduced expression of FHF markers and increased expression of SHF markers in cardiac progenitor cells. hPSC-CMs arising from the SHF-like progenitor cells showed an RV-like gene expression pattern and exhibited phenotypic differences in spontaneous contraction rate, Ca2+ transients, and cell size compared to control LV-like cardiomyocytes.
Conclusion This study establishes methodology to generate RV-like hPSC-CMs to support the development of disease modeling research using chamber-specific hPSC-CMs. en-copyright= kn-copyright= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatanosakaYuki en-aut-sei=Katanosaka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IidaToshihiro en-aut-sei=Iida en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KusumotoDai en-aut-sei=Kusumoto en-aut-mei=Dai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatoRyushi en-aut-sei=Sato en-aut-mei=Ryushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AdachiRiki en-aut-sei=Adachi en-aut-mei=Riki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimizuSatoshi en-aut-sei=Shimizu en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KurokawaJunko en-aut-sei=Kurokawa en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshidaMasashi en-aut-sei=Yoshida en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NaruseKeiji en-aut-sei=Naruse en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NishidaMikako en-aut-sei=Nishida en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=UdonoHeiichiro en-aut-sei=Udono en-aut-mei=Heiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ZhangJianhua en-aut-sei=Zhang en-aut-mei=Jianhua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KampTimothy J. en-aut-sei=Kamp en-aut-mei=Timothy J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Cardiovascular Physiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Biomedical Informatics and Molecular Biology, The Sakaguchi Laboratory, Keio University School of Medicine kn-affil= affil-num=6 en-affil=Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka kn-affil= affil-num=7 en-affil=Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka kn-affil= affil-num=8 en-affil=Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka kn-affil= affil-num=9 en-affil=Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Cardiovascular Therapeutics, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Cardiovascular Physiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Medicine, University of Wisconsin School of Medicine and Public Health kn-affil= affil-num=18 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Medicine, University of Wisconsin School of Medicine and Public Health kn-affil= affil-num=20 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Human pluripotent stem cell-derived cardiomyocytes kn-keyword=Human pluripotent stem cell-derived cardiomyocytes en-keyword=Anterior second heart field kn-keyword=Anterior second heart field en-keyword=Right ventricle kn-keyword=Right ventricle en-keyword=Bone morphogenetic protein kn-keyword=Bone morphogenetic protein END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250929 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Establishment of a regenerative endodontic procedures model of mature mouse teeth and evaluation of the wound healing process en-subtitle= kn-subtitle= en-abstract= kn-abstract=As the pulp regeneration for non-vital teeth is one of the ultimate clinical achievements, regenerative endodontic procedures (REPs) have become the most explored treatment modality. In this technique, periodontal tissue is guided from the apical region into the root canal and pulp chamber to promote attachment. It is well established that immature teeth are effective targets for treatment. However, the indications for this treatment have not yet expanded sufficiently to encompass mature teeth with closed apical apex. In the present study, a mouse model of REPs in mature teeth was established, employing the maxillary first molar mesial root. μCT analyses disclosed that the distance from the occlusal surface to the physiological apex of the maxillary first molar mesial root in mice is 2.14 mm ± 0.08 mm, and the distance from the occlusal surface to the periapical alveolar bone is 2.46 mm ± 0.10 mm. Mesial root canal was treated with several sizes of k-files, and 15# k-file was identified as the most suitable k-file for use (P = 0.0007). During the regenerative process, spindle-shaped fibroblast-like cells, fibrous tissue formation, and mineralized tissue formation were identified on days 14 and 28. This study demonstrated that it is feasible to use the maxillary first molar mesial root as a REPs model for mature teeth and provided a detailed protocol and analysis of the healing process. en-copyright= kn-copyright= en-aut-name=WangXiuting en-aut-sei=Wang en-aut-mei=Xiuting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiShigeki en-aut-sei=Suzuki en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsaiShin-Ho en-aut-sei=Tsai en-aut-mei=Shin-Ho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagasakiKarin en-aut-sei=Nagasaki en-aut-mei=Karin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FahrezaRahmad Rifqi en-aut-sei=Fahreza en-aut-mei=Rahmad Rifqi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriMasato en-aut-sei=Omori en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamadaSatoru en-aut-sei=Yamada en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=2 en-affil=Department of Operative Dentistry, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Operative Dentistry, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=5 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=6 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=7 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= en-keyword=Regenerative endodontic procedures kn-keyword=Regenerative endodontic procedures en-keyword=Establishment of protocols kn-keyword=Establishment of protocols en-keyword=Mouse experimental model kn-keyword=Mouse experimental model en-keyword=Mature teeth kn-keyword=Mature teeth END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=18 article-no= start-page=2927 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250911 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lacticaseibacillus rhamnosus Probio-M9 Alters the Gut Microbiota and Mitigates Pulmonary Hypertension in a Rat Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Intestinal microbiota plays an important role in the progression of pulmonary hypertension (PH). Colostrum-derived Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9) has shown protective effects against inflammation and remodeling. We investigated whether Probio-M9 supplementation could improve the pathology of PH. Methods: The monocrotaline (MCT)-induced PH model rats are created followed by Probio-M9 treatment. Microbiota and pathological analyses were performed to investigate the therapeutic effects of Probio-M9. Results: Probio-M9 significantly suppressed cardiovascular remodeling and reduced mortality in rats. Analysis of the fecal microbiota revealed that Probio-M9 significantly altered the gut microbiota of MCT model rats. Specifically, Alistipes sp009774895 and Duncaniella muris populations increased, whereas Limosilactobacillus reuteri_D, Ligilactobacillus apodeme and Monoglobus sp900542675 decreased compared to those in the MCT group. Focusing on the expression of GPNMB in macrophages and the localization of CD44, we found that the number of these cells increased in the MCT group but significantly decreased with Probio-M9 treatment. In lung tissue from PH patients, more GPNMB-positive macrophages were found than non-PH lungs, and an increase in CD44-positive cells was confirmed in the vicinity of GPNMB. Conclusions: Probio-M9 had a significant impact on the intestinal microbiota and GPNMB/CD44 positive cells in the lungs of PH rats. en-copyright= kn-copyright= en-aut-name=ZhaoZhixin en-aut-sei=Zhao en-aut-mei=Zhixin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiGaopeng en-aut-sei=Li en-aut-mei=Gaopeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhmichiKiyomi en-aut-sei=Ohmichi en-aut-mei=Kiyomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LiXiaodong en-aut-sei=Li en-aut-mei=Xiaodong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZhaoFeiyan en-aut-sei=Zhao en-aut-mei=Feiyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshikawaKaori en-aut-sei=Ishikawa en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshikawaRyou en-aut-sei=Ishikawa en-aut-mei=Ryou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YokotaNaoya en-aut-sei=Yokota en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SunZhihong en-aut-sei=Sun en-aut-mei=Zhihong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KuraharaLin Hai en-aut-sei=Kurahara en-aut-mei=Lin Hai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University kn-affil= affil-num=3 en-affil=Department of Diagnostic Pathology, Kagawa University Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University kn-affil= affil-num=5 en-affil=Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University kn-affil= affil-num=6 en-affil=Department of General Medicine, Kagawa University Hospital kn-affil= affil-num=7 en-affil=Department of Diagnostic Pathology, Kagawa University Hospital kn-affil= affil-num=8 en-affil=Center for Advanced Heart Failure, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University kn-affil= affil-num=10 en-affil=Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University kn-affil= affil-num=11 en-affil=Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University kn-affil= en-keyword=pulmonary artery remodeling kn-keyword=pulmonary artery remodeling en-keyword=probiotics kn-keyword=probiotics en-keyword=gut microbiota kn-keyword=gut microbiota en-keyword=macrophages kn-keyword=macrophages en-keyword=GPNMB kn-keyword=GPNMB en-keyword=CD44 kn-keyword=CD44 END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=9 article-no= start-page=660 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250921 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Application of LMM-Derived Prompt-Based AIGC in Low-Altitude Drone-Based Concrete Crack Monitoring en-subtitle= kn-subtitle= en-abstract= kn-abstract=In recent years, large multimodal models (LMMs), such as ChatGPT 4o and DeepSeek R1—artificial intelligence systems capable of multimodal (e.g., image and text) human–computer interaction—have gained traction in industrial and civil engineering applications. Concurrently, insufficient real-world drone-view data (specifically close-distance, high-resolution imagery) for civil engineering scenarios has heightened the importance of artificially generated content (AIGC) or synthetic data as supplementary inputs. AIGC is typically produced via text-to-image generative models (e.g., Stable Diffusion, DALL-E) guided by user-defined prompts. This study leverages LMMs to interpret key parameters for drone-based image generation (e.g., color, texture, scene composition, photographic style) and applies prompt engineering to systematize these parameters. The resulting LMM-generated prompts were used to synthesize training data for a You Only Look Once version 8 segmentation model (YOLOv8-seg). To address the need for detailed crack-distribution mapping in low-altitude drone-based monitoring, the trained YOLOv8-seg model was evaluated on close-distance crack benchmark datasets. The experimental results confirm that LMM-prompted AIGC is a viable supplement for low-altitude drone crack monitoring, achieving >80% classification accuracy (images with/without cracks) at a confidence threshold of 0.5. en-copyright= kn-copyright= en-aut-name=PanShijun en-aut-sei=Pan en-aut-mei=Shijun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FanZhun en-aut-sei=Fan en-aut-mei=Zhun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=QinShujia en-aut-sei=Qin en-aut-mei=Shujia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KojimaTakashi en-aut-sei=Kojima en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= affil-num=1 en-affil=Shenzhen Institute for Advanced Study, UESTC, University of Electronic Science and Technology of China kn-affil= affil-num=2 en-affil=Shenzhen Institute for Advanced Study, UESTC, University of Electronic Science and Technology of China kn-affil= affil-num=3 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Shenzhen Academy of Robotics kn-affil= affil-num=5 en-affil=TOKEN C.E.E. Consultants Co., Ltd. kn-affil= affil-num=6 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=large multimodal model kn-keyword=large multimodal model en-keyword=unmanned aerial vehicle kn-keyword=unmanned aerial vehicle en-keyword=crack kn-keyword=crack END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=1333 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250816 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phosphorylated pullulan as a local drug delivery matrix for cationic antibacterial chemicals to prevent oral biofilm en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Preventing oral infections, such as oral caries and periodontal disease, helps reduce the risks of various systemic diseases. In this study, the polysaccharide pullulan produced by the black yeast Aureobasidium pullulans was modified in combination with the cationic surfactant cetylpyridinium chloride (CPC) to create a local drug delivery system, and its antibacterial potential on oral bacteria was examined in vitro.
Methods Pullulan was phosphorylated at the CH2OH residue of α6 in the maltotriose structure and mixed with CPC. Bacterial attachment of cariogenic Streptococcus mutans on hydroxyapatite plates (HAPs) treated with the phosphorylated pullulan (PP) and CPC compound (0.01% PP and 0.001– 0.03% CPC, and vice versa) was assessed by observing bacteria using a field emission scanning electron microscope (FE-SEM) and quantified through 16 S rRNA amplification via real-time polymerase chain reaction (PCR). Additionally, the quartz crystal microbalance (QCM) method was employed to evaluate the sustained release of CPC.
Results PP-CPC compound maintained significant bactericidal activity even at 0.01%, which is one-fifth of the conventional applicable concentration of CPC. Additionally, a residual mixture was detected by the hydroxyapatite sensor of the crystal oscillator microbalance detector, suggesting an unknown molecular interaction that enables the sustained release of CPC after attachment to hydroxyapatite.
Conclusions The combination of PP and CPC may contribute to the low concentration and effective prevention of oral infections, such as dental caries. en-copyright= kn-copyright= en-aut-name=Namba-KoideNaoko en-aut-sei=Namba-Koide en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaYasuhiro en-aut-sei=Yoshida en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkiharaTakumi en-aut-sei=Okihara en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawataYusuke en-aut-sei=Kawata en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItoMasahiro en-aut-sei=Ito en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ItoTakashi en-aut-sei=Ito en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Takeuchi-HatanakaKazu en-aut-sei=Takeuchi-Hatanaka en-aut-mei=Kazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=3 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School kn-affil= affil-num=4 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=7 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Phosphorylated Pullulan kn-keyword=Phosphorylated Pullulan en-keyword=Local drug delivery system kn-keyword=Local drug delivery system en-keyword=Cationic antimicrobial agents kn-keyword=Cationic antimicrobial agents en-keyword=Cetylpyridinium chloride kn-keyword=Cetylpyridinium chloride en-keyword=Oral biofilm kn-keyword=Oral biofilm END start-ver=1.4 cd-journal=joma no-vol=130 cd-vols= no-issue=1 article-no= start-page=e2024JB030704 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Reduced Thermal Conductivity of Hydrous Aluminous Silica and Calcium Ferrite‐Type Phase Promote Water Transportation to Earth's Deep Mantle en-subtitle= kn-subtitle= en-abstract= kn-abstract=Subduction of oceanic slabs introduces chemical heterogeneities in the Earth's interior, which could further induce thermal, seismic, and geodynamical anomalies. Thermal conductivity of slab minerals crucially controls the thermal evolution and dynamics of the subducted slab and ambient mantle, while such an important transport property remains poorly constrained. Here we have precisely measured high pressure-temperature thermal conductivity of hydrous aluminous post-stishovite (ΛHy-Al-pSt) and aluminum-rich calcium ferrite-type phase (ΛCF), two important minerals in the subducted basaltic crust in the lower mantle. Compared to the dry aluminous stishovite and pure stishovite, hydration substantially reduces the ΛHy-Al-pSt, resulting in ∼9.7–13.3 W m−1 K−1 throughout the lower mantle. Surprisingly, the ΛCF remains at ∼3–3.8 W m−1 K−1 in the lower mantle, few-folds lower than previously assumed. Our data modeling offers better constraints on the thermal conductivity of the subducted oceanic crust from mantle transition zone to the lowermost mantle region, which is less thermally conductive than previously modeled. Our findings suggest that if the post-stishovite carries large amounts of water to the lower mantle, the poorer heat conduction through the basaltic crust reduces the slab's temperature, which not only allows the slab bringing more hydrous minerals to greater depth, but also increases slab's density and viscosity, potentially impacting the stability of heterogeneous structures at the lowermost mantle. en-copyright= kn-copyright= en-aut-name=HsiehWen‐Pin en-aut-sei=Hsieh en-aut-mei=Wen‐Pin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DeschampsFrédéric en-aut-sei=Deschamps en-aut-mei=Frédéric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsaoYi‐Chi en-aut-sei=Tsao en-aut-mei=Yi‐Chi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChangJen‐Wei en-aut-sei=Chang en-aut-mei=Jen‐Wei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=CrinitiGiacomo en-aut-sei=Criniti en-aut-mei=Giacomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Institute of Earth Sciences, Academia Sinica kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=Institute of Earth Sciences, Academia Sinica kn-affil= affil-num=4 en-affil=Institute of Earth Sciences, Academia Sinica kn-affil= affil-num=5 en-affil=Institute of Earth Sciences, Academia Sinica kn-affil= affil-num=6 en-affil=Earth and Planets Laboratory, Carnegie Institution for Science kn-affil= en-keyword=thermal conductivity kn-keyword=thermal conductivity en-keyword=post-stishovite kn-keyword=post-stishovite en-keyword=calcium ferrite-type phase kn-keyword=calcium ferrite-type phase en-keyword=basaltic crust kn-keyword=basaltic crust END start-ver=1.4 cd-journal=joma no-vol=142 cd-vols= no-issue= article-no= start-page=104967 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cross-feeding between beneficial and pathogenic bacteria to utilize eukaryotic host cell-derived sialic acids and bacteriophages shape the pathogen-host interface milieu en-subtitle= kn-subtitle= en-abstract= kn-abstract=Under an inflamed-intestinal milieu, increased free sialic acids are associated with the overgrowth of some pathogenic bacterial strains. Recently, the protective immunomodulatory activity of gut bacteriophages (phages) has also been highlighted. However, the role of phages in triple reciprocal interactions between pathogenic bacteria, beneficial bacteria, and their host cell sialic acids has not been studied so far. We established a sialidase-explicit model in which beneficial and pathogenic bacteria interact through cross-feeding and competition for free sialic acid using a human triple co-culture cell model incorporating colonocytes (T84 cells), monocytes (THP-1 cells), and hepatocytes (Huh7 cells). Triple co-cultured cells were challenged with Gram-positive Bifidobacterium bifidum (B. bifidum) and Gram-negative Pseudomonas aeruginosa PAO1 (P. a PAO1) in the absence or presence of its KPP22 phage in two different cell culture mediums: 1) standard Dulbecco's Modified Eagle Medium (DMEM) and 2) DMEM with 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA). Changes in physiological, functional, and structural health markers of stimulated cocultured cells were evaluated. The concentrations of sialic acid and pro-inflammatory cytokines in the cell culture supernatants were quantified. P. a PAO1 triggered the release of interleukin 6 and 8 (IL-6 and IL-8), accompanied by increased levels of free sialic acid, reduced viability of co-cultured cells, and disrupted the integrity of the cellular monolayer. These disruptive effects were markedly attenuated by KPP22 phage and B. bifidum. In addition to well-documented differences in the structure and composition of the bacterial cell walls of Gram-negative pathogenic bacteria and bifidobacteria, two distinct factors seem to be pivotal in modulating the pathogen-host interface milieu: (i) the presence of phages and (ii) the utilization of free sialic acids secreted from host cells by bifidobacteria. en-copyright= kn-copyright= en-aut-name=GhadimiDarab en-aut-sei=Ghadimi en-aut-mei=Darab kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Fölster-HolstRegina en-aut-sei=Fölster-Holst en-aut-mei=Regina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BlömerSophia en-aut-sei=Blömer en-aut-mei=Sophia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EbsenMichael en-aut-sei=Ebsen en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RöckenChristoph en-aut-sei=Röcken en-aut-mei=Christoph kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuzakiShigenobu en-aut-sei=Matsuzaki en-aut-mei=Shigenobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BockelmannWilhelm en-aut-sei=Bockelmann en-aut-mei=Wilhelm kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= affil-num=2 en-affil=Clinic of Dermatology, Venerology und Allergology, University Hospital Schleswig-Holstein kn-affil= affil-num=3 en-affil=Clinic of Dermatology, Venerology und Allergology, University Hospital Schleswig-Holstein kn-affil= affil-num=4 en-affil=Städtisches MVZ Kiel GmbH (Kiel City Hospital), Department of Pathology kn-affil= affil-num=5 en-affil=Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein kn-affil= affil-num=6 en-affil=Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University kn-affil= affil-num=8 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= en-keyword=Bacterial sialidase kn-keyword=Bacterial sialidase en-keyword=Inflammation kn-keyword=Inflammation en-keyword=Cytokines kn-keyword=Cytokines en-keyword=Infection kn-keyword=Infection en-keyword=Bifidobacteria kn-keyword=Bifidobacteria en-keyword=Phages kn-keyword=Phages END start-ver=1.4 cd-journal=joma no-vol=243 cd-vols= no-issue= article-no= start-page=120539 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Organic solvent transport through reduced graphene oxide membranes with controlled oxygen content en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent advances in membranes based on 2-dimensional (2D) materials have enabled precise control over angstrom-scale pores, providing a unique platform for studying diverse mass transport mechanisms. In this work, we systematically investigate the transport of solvent vapors through 2D channels made of graphene oxide (GO) laminates with precisely controlled oxygen content. Using in-situ chemical reduction of GO with vitamin C, we fabricated reduced GO membranes (VRGMs) with oxygen content systematically decreased from 31.6 % (pristine GO) to 24.0 % (VRGM-maximum reduction). Vapor permeability measurements showed a distinct correlation between oxygen functional groups and solvent transport behaviour. Specifically, non-polar hexane exhibits 114 % of enhanced permeance through the reduced membranes with larger graphitic domains, while the permeance of water decreases by 55 %. With the support of density functional theory (DFT) simulations, we modelled the hydrogen-bond and dispersion complexes between the solvents and GO and calculated the complexation energies. The simulation results suggest that polar molecules interact with the oxygen functional groups of GO via a hydrogen-bond network, supporting in-plane transport. In contrast, van der Waals forces drive the transport of low-polarity solvents along the graphitic domains of the 2D channel in reduced GO membranes. Our findings provide potential strategies for future design of organic solvent nanofiltration membranes. en-copyright= kn-copyright= en-aut-name=ChenHongzhe en-aut-sei=Chen en-aut-mei=Hongzhe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LinTongxi en-aut-sei=Lin en-aut-mei=Tongxi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RamadhanZeno Rizqi en-aut-sei=Ramadhan en-aut-mei=Zeno Rizqi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=RawalAditya en-aut-sei=Rawal en-aut-mei=Aditya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KartonAmir en-aut-sei=Karton en-aut-mei=Amir kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=RenXiaojun en-aut-sei=Ren en-aut-mei=Xiaojun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=JoshiRakesh en-aut-sei=Joshi en-aut-mei=Rakesh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=School of Materials Science and Engineering, University of New South Wales Sydney kn-affil= affil-num=2 en-affil=School of Materials Science and Engineering, University of New South Wales Sydney kn-affil= affil-num=3 en-affil=Electron Microscope Unit, University of New South Wales kn-affil= affil-num=4 en-affil=Mark Wainwright Analytical Centre, University of New South Wales kn-affil= affil-num=5 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=6 en-affil=School of Science and Technology, University of New England kn-affil= affil-num=7 en-affil=School of Materials Science and Engineering, University of New South Wales Sydney kn-affil= affil-num=8 en-affil=School of Materials Science and Engineering, University of New South Wales Sydney kn-affil= en-keyword=Graphene oxide kn-keyword=Graphene oxide en-keyword=Organic solvent nanofiltration kn-keyword=Organic solvent nanofiltration END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=3 article-no= start-page=e70004 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=Oregon Wolfe barley genetic stocks – Research and teaching tools for next generation scientists en-subtitle= kn-subtitle= en-abstract= kn-abstract=The Oregon Wolfe Barley (OWB) mapping population (Reg. no. MP-4, NSL 554937 MAP) is a resource for genetics research and instruction. The OWBs are a set of doubled haploid barley (Hordeum vulgare L.) lines developed at Oregon State University from the F1 of a cross between Dr. Robert Wolfe's dominant and recessive marker stocks. Exhibiting a high level of genetic and phenotypic diversity, the OWBs are used throughout the world as a research tool for barley genetics. To date, these endeavors have led to 56 peer-reviewed publications, as well as three reports in the Barley Genetics Newsletter. At the same time, the OWBs are widely used as an instructor resource at the K–12, undergraduate, graduate, and professional levels. They are currently used at universities and/or institutes in German, Italy, Norway, Spain, and the United States and are currently being developed further for educational use in other countries. Genotype and phenotype data, lesson plans, and seed availability information are available herein and online. en-copyright= kn-copyright= en-aut-name=KrauseMargaret R. en-aut-sei=Krause en-aut-mei=Margaret R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ArbelaezJuan David en-aut-sei=Arbelaez en-aut-mei=Juan David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsdalÅsmund en-aut-sei=Asdal en-aut-mei=Åsmund kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BelkodjaRamzi en-aut-sei=Belkodja en-aut-mei=Ramzi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BouryNancy en-aut-sei=Boury en-aut-mei=Nancy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BlakeVictoria C. en-aut-sei=Blake en-aut-mei=Victoria C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BrownPatrick J. en-aut-sei=Brown en-aut-mei=Patrick J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CasasAna en-aut-sei=Casas en-aut-mei=Ana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=CistuéLuis en-aut-sei=Cistué en-aut-mei=Luis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Farré‐MartínezAlba en-aut-sei=Farré‐Martínez en-aut-mei=Alba kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FiskScott en-aut-sei=Fisk en-aut-mei=Scott kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FuerstGregory S. en-aut-sei=Fuerst en-aut-mei=Gregory S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=GiménezEstela en-aut-sei=Giménez en-aut-mei=Estela kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Guijarro‐RealCarla en-aut-sei=Guijarro‐Real en-aut-mei=Carla kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=GuthrieKaty en-aut-sei=Guthrie en-aut-mei=Katy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HalsteadMargaret en-aut-sei=Halstead en-aut-mei=Margaret kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HelgersonLaura en-aut-sei=Helgerson en-aut-mei=Laura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IgartuaErnesto en-aut-sei=Igartua en-aut-mei=Ernesto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=LillemoMorten en-aut-sei=Lillemo en-aut-mei=Morten kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=Martínez‐GarcíaMarina en-aut-sei=Martínez‐García en-aut-mei=Marina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=Martínez‐SubiràMariona en-aut-sei=Martínez‐Subirà en-aut-mei=Mariona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=McCouchSusan en-aut-sei=McCouch en-aut-mei=Susan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=McGheeLaurie en-aut-sei=McGhee en-aut-mei=Laurie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=NickolsTravis en-aut-sei=Nickols en-aut-mei=Travis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=PetersNick en-aut-sei=Peters en-aut-mei=Nick kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=PorterRaymond en-aut-sei=Porter en-aut-mei=Raymond kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=RomagosaIgnacio en-aut-sei=Romagosa en-aut-mei=Ignacio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=RuudAnja Karine en-aut-sei=Ruud en-aut-mei=Anja Karine kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=SatoKazuhiro en-aut-sei=Sato en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=SalviSilvio en-aut-sei=Salvi en-aut-mei=Silvio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=SangiorgiGiuseppe en-aut-sei=Sangiorgi en-aut-mei=Giuseppe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=SchüllerRebekka en-aut-sei=Schüller en-aut-mei=Rebekka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=SenTaner Z. en-aut-sei=Sen en-aut-mei=Taner Z. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=SorianoJosé Miguel en-aut-sei=Soriano en-aut-mei=José Miguel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=StuparRobert M. en-aut-sei=Stupar en-aut-mei=Robert M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=TingTo‐Chia en-aut-sei=Ting en-aut-mei=To‐Chia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=ViningKelly en-aut-sei=Vining en-aut-mei=Kelly kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=von KorffMaria en-aut-sei=von Korff en-aut-mei=Maria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=WallaAgatha en-aut-sei=Walla en-aut-mei=Agatha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=WangDiane R. en-aut-sei=Wang en-aut-mei=Diane R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=WaughRobbie en-aut-sei=Waugh en-aut-mei=Robbie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=WiseRoger P. en-aut-sei=Wise en-aut-mei=Roger P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=WolfeRobert en-aut-sei=Wolfe en-aut-mei=Robert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=YaoEric en-aut-sei=Yao en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=HayesPatrick M. en-aut-sei=Hayes en-aut-mei=Patrick M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= affil-num=1 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=2 en-affil=Department of Crop Sciences, University of Illinois at Urbana-Champaign kn-affil= affil-num=3 en-affil=Nordic Genetic Resource Centre kn-affil= affil-num=4 en-affil=CIHEAM-Zaragoza kn-affil= affil-num=5 en-affil=Department of Plant Pathology, Entomology, and Microbiology, Iowa State University kn-affil= affil-num=6 en-affil=Department of Plant Sciences and Plant Pathology, Montana State University kn-affil= affil-num=7 en-affil=Department of Plant Sciences, University of California-Davis kn-affil= affil-num=8 en-affil=Departamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSIC kn-affil= affil-num=9 en-affil=Departamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSIC kn-affil= affil-num=10 en-affil=AGROTECNIO-CERCA Center, Universidad de Lleida kn-affil= affil-num=11 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=12 en-affil=U.S. Department of Agriculture-Agricultural Research Service, Corn Insects and Crop Genetics Research Unit, Iowa State University kn-affil= affil-num=13 en-affil=Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid kn-affil= affil-num=14 en-affil=Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid kn-affil= affil-num=15 en-affil=Department of Agronomy and Plant Genetics, University of Minnesota kn-affil= affil-num=16 en-affil=Aardevo North America kn-affil= affil-num=17 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=18 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=19 en-affil=Departamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSIC kn-affil= affil-num=20 en-affil=Department of Plant Sciences, Norwegian University of Life Sciences kn-affil= affil-num=21 en-affil=Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid kn-affil= affil-num=22 en-affil=AGROTECNIO-CERCA Center, Universidad de Lleida kn-affil= affil-num=23 en-affil=Plant Breeding and Genetics Section, School of Integrative Plant Science, Cornell University kn-affil= affil-num=24 en-affil=Colfax-Mingo Community High School kn-affil= affil-num=25 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=26 en-affil=Department of Plant Pathology, Entomology, and Microbiology, Iowa State University kn-affil= affil-num=27 en-affil=Haupert Institute for Agricultural Studies, Huntington University kn-affil= affil-num=28 en-affil=AGROTECNIO-CERCA Center, Universidad de Lleida kn-affil= affil-num=29 en-affil=Department of Plant Sciences, Norwegian University of Life Sciences kn-affil= affil-num=30 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=31 en-affil=Department of Agricultural and Food Sciences, University of Bologna kn-affil= affil-num=32 en-affil=Department of Agricultural and Food Sciences, University of Bologna kn-affil= affil-num=33 en-affil=Department of Crop Sciences, University of Illinois at Urbana-Champaign kn-affil= affil-num=34 en-affil=Crop Improvement and Genetics Research Unit, U.S. Department of Agriculture-Agricultural Research Service kn-affil= affil-num=35 en-affil=AGROTECNIO-CERCA Center, Universidad de Lleida kn-affil= affil-num=36 en-affil=Department of Agronomy and Plant Genetics, University of Minnesota kn-affil= affil-num=37 en-affil=Agronomy Department, Purdue University kn-affil= affil-num=38 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=39 en-affil=Institute of Plant Genetics, Heinrich-Heine-Universität Düsseldorf kn-affil= affil-num=40 en-affil=Institute of Plant Genetics, Heinrich-Heine-Universität Düsseldorf kn-affil= affil-num=41 en-affil=Agronomy Department, Purdue University kn-affil= affil-num=42 en-affil=Division of Plant Sciences, School of Life Sciences, University of Dundee kn-affil= affil-num=43 en-affil=Department of Plant Pathology, Entomology, and Microbiology, Iowa State University kn-affil= affil-num=44 en-affil=Agriculture and Agri-Food Canada kn-affil= affil-num=45 en-affil=Crop Improvement and Genetics Research Unit, U.S. Department of Agriculture-Agricultural Research Service kn-affil= affil-num=46 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=9 article-no= start-page=846 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240905 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Unveiling a New Antimicrobial Peptide with Efficacy against P. aeruginosa and K. pneumoniae from Mangrove-Derived Paenibacillus thiaminolyticus NNS5-6 and Genomic Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study focused on the discovery of the antimicrobial peptide (AMP) derived from mangrove bacteria. The most promising isolate, NNS5-6, showed the closest taxonomic relation to Paenibacillus thiaminolyticus, with the highest similarity of 74.9%. The AMP produced by Paenibacillus thiaminolyticus NNS5-6 exhibited antibacterial activity against various Gram-negative pathogens, especially Pseudomonas aeruginosa and Klebsiella pneumoniae. The peptide sequence consisted of 13 amino acids and was elucidated as Val-Lys-Gly-Asp-Gly-Gly-Pro-Gly-Thr-Val-Tyr-Thr-Met. The AMP mainly exhibited random coil and antiparallel beta-sheet structures. The stability study indicated that this AMP was tolerant of various conditions, including proteolytic enzymes, pH (1.2–14), surfactants, and temperatures up to 40 °C for 12 h. The AMP demonstrated 4 µg/mL of MIC and 4–8 µg/mL of MBC against both pathogens. Time-kill kinetics showed that the AMP acted in a time- and concentration-dependent manner. A cell permeability assay and scanning electron microscopy revealed that the AMP exerted the mode of action by disrupting bacterial membranes. Additionally, nineteen biosynthetic gene clusters of secondary metabolites were identified in the genome. NNS5-6 was susceptible to various commonly used antibiotics supporting the primary safety requirement. The findings of this research could pave the way for new therapeutic approaches in combating antibiotic-resistant pathogens. en-copyright= kn-copyright= en-aut-name=SermkaewNamfa en-aut-sei=Sermkaew en-aut-mei=Namfa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AtipairinApichart en-aut-sei=Atipairin en-aut-mei=Apichart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KrobthongSucheewin en-aut-sei=Krobthong en-aut-mei=Sucheewin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AonbangkhenChanat en-aut-sei=Aonbangkhen en-aut-mei=Chanat kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YingchutrakulYodying en-aut-sei=Yingchutrakul en-aut-mei=Yodying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SongnakaNuttapon en-aut-sei=Songnaka en-aut-mei=Nuttapon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=School of Pharmacy, Walailak University kn-affil= affil-num=2 en-affil=School of Pharmacy, Walailak University kn-affil= affil-num=3 en-affil=Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry, Faculty of Science, Chulalongkorn University kn-affil= affil-num=4 en-affil=Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry, Faculty of Science, Chulalongkorn University kn-affil= affil-num=5 en-affil=National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency kn-affil= affil-num=6 en-affil=Department of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=School of Pharmacy, Walailak University kn-affil= en-keyword=antimicrobial peptide kn-keyword=antimicrobial peptide en-keyword=antimicrobial resistance kn-keyword=antimicrobial resistance en-keyword=bacterial genome kn-keyword=bacterial genome en-keyword=biosynthetic gene cluster kn-keyword=biosynthetic gene cluster en-keyword=Klebsiella pneumoniae kn-keyword=Klebsiella pneumoniae en-keyword=Mangrove kn-keyword=Mangrove en-keyword=mass spectrometry kn-keyword=mass spectrometry en-keyword=NNS5-6 kn-keyword=NNS5-6 en-keyword=Paenibacillus thiaminolyticus kn-keyword=Paenibacillus thiaminolyticus en-keyword=Pseudomonas aeruginosa kn-keyword=Pseudomonas aeruginosa END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue= article-no= start-page=100277 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=Development of a technique to identify μm-sized organic matter in asteroidal material: An approach using machine learning en-subtitle= kn-subtitle= en-abstract= kn-abstract=Asteroidal materials contain organic matter (OM), which records a number of extraterrestrial environments and thus provides a record of Solar System processes. OM contain essential compounds for the origin of life. To understand the origin and evolution of OM, systematic identification and detailed observation using in-situ techniques is required. While both nm- and μm-sized OM were studied previously, only a small portion of a given sample surface was investigated in each study. Here, a novel workflow was developed and applied to identify and classify μm-sized OM on mm-sized asteroidal materials. The workflow involved image processing and machine learning, enabling a comprehensive and non-biased way of identifying, classifying, and measuring the properties of OM. We found that identifying OM is more accurate by classification with machine learning than by clustering. On the approach of classification with machine learning, five algorithms were tested. The random forest algorithm was selected as it scored the highest in 4 out of 5 accuracy parameters during evaluation. The workflow gave modal OM abundances that were consistent with those identified manually, demonstrating that the workflow can accurately identify 1-15 μm-sized OM. The size distribution of OM was modeled using the power-law distribution, giving slope α values that were consistent with fragmentation processes. The shape of the OM was quantified using circularity and solidity, giving a positive correlation and indicating these properties are closely related. Overall, the workflow enabled identification of many OM quickly and accurately and the obtainment of chemical and petrographic information. Such information can help the selection of OM for further in-situ techniques, and elucidate the origin and evolution of OM preserved in asteroidal materials. en-copyright= kn-copyright= en-aut-name=KumarRahul en-aut-sei=Kumar en-aut-mei=Rahul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiKatsura en-aut-sei=Kobayashi en-aut-mei=Katsura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PotiszilChristian en-aut-sei=Potiszil en-aut-mei=Christian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KunihiroTak en-aut-sei=Kunihiro en-aut-mei=Tak kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=The Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=The Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=The Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= affil-num=4 en-affil=The Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University kn-affil= en-keyword=Asteroidal material kn-keyword=Asteroidal material en-keyword=Organic matter kn-keyword=Organic matter en-keyword=Carbonaceous chondrites kn-keyword=Carbonaceous chondrites en-keyword=RyuguImage processing kn-keyword=RyuguImage processing en-keyword=Machine learning kn-keyword=Machine learning en-keyword=Size distribution kn-keyword=Size distribution END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=10 article-no= start-page=4724 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250515 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Stem Cell Factors BAM1 and WOX1 Suppressing Longitudinal Cell Division of Margin Cells Evoked by Low-Concentration Auxin in Young Cotyledon of Arabidopsis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Highly differentiated tissues and organs play essential biological functions in multicellular organisms. Coordination of organ developmental process with tissue differentiation is necessary to achieve proper development of mature organs, but mechanisms for such coordination are not well understood. We used cotyledon margin cells from Arabidopsis plant as a new model system to investigate cell elongation and cell division during organ growth and found that margin cells endured a developmental phase transition from the “elongation” phase to the “elongation and division” phase at the early stage in germinating seedlings. We also discovered that the stem cell factors BARELY ANY MERISTEM 1 (BAM1) and WUSCHEL-related homeobox1 (WOX1) are involved in the regulation of margin cell developmental phase transition. Furthermore, exogenous auxin treatment (1 nanomolar,nM) promotes cell division, especially longitudinal cell division. This promotion of cell division did not occur in bam1 and wox1 mutants. Based on these findings, we hypothesized a new “moderate auxin concentration” model which emphasizes that a moderate auxin concentration is the key to triggering the developmental transition of meristematic cells. en-copyright= kn-copyright= en-aut-name=JiangYuli en-aut-sei=Jiang en-aut-mei=Yuli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiangJian en-aut-sei=Liang en-aut-mei=Jian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangChunyan en-aut-sei=Wang en-aut-mei=Chunyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanLi en-aut-sei=Tan en-aut-mei=Li kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawanoYoji en-aut-sei=Kawano en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagawaShingo en-aut-sei=Nagawa en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Institute for Translational Brain Reaearch, Fudan University kn-affil= affil-num=2 en-affil=Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences kn-affil= affil-num=3 en-affil=Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences kn-affil= affil-num=4 en-affil=Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences kn-affil= en-keyword=BAM1 kn-keyword=BAM1 en-keyword=WOX1 kn-keyword=WOX1 en-keyword=margin cells kn-keyword=margin cells en-keyword=auxin kn-keyword=auxin END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=17 article-no= start-page=8643 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250905 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Anti-HMGB1 Antibody Therapy Ameliorates Spinal Cord Ischemia–Reperfusion Injury in Rabbits en-subtitle= kn-subtitle= en-abstract= kn-abstract=Spinal cord ischemia–reperfusion (SCI/R) injury remains a major clinical challenge with limited therapeutic options. High-mobility group box 1 (HMGB1), a proinflammatory mediator released during cellular stress, has been implicated in the pathogenesis of ischemia–reperfusion-induced neural damage. In this study, we investigated the neuroprotective potential of the anti-HMGB1 monoclonal antibody (mAb) in a rabbit model of SCI/R injury. Male New Zealand White rabbits were anesthetized and subjected to 11 min of abdominal aortic occlusion using a micro-bulldog clamp following heparinization. Anti-HMGB1 mAb or control IgG was administered intravenously immediately after reperfusion and again at 6 h post-reperfusion. Neurological function was assessed at 6, 24, and 48 h after reperfusion using the modified Tarlov scoring system. The rabbits were euthanized 48 h after reperfusion for spinal cord and blood sampling. Treatment with anti-HMGB1 mAb significantly improved neurological outcomes, reduced the extent of spinal cord infarction, preserved motor neuron viability, and decreased the presence of activated microglia and infiltrating neutrophils. Furthermore, it attenuated apoptosis, oxidative stress, and inflammatory responses in the spinal cord, and helped maintain the integrity of the blood–spinal cord barrier. These findings suggest that anti-HMGB1 mAb may serve as a promising therapeutic agent for SCI/R injury. en-copyright= kn-copyright= en-aut-name=MuraokaGenya en-aut-sei=Muraoka en-aut-mei=Genya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiYasuhiro en-aut-sei=Fujii en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiuKeyue en-aut-sei=Liu en-aut-mei=Keyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=QiaoHandong en-aut-sei=Qiao en-aut-mei=Handong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WangDengli en-aut-sei=Wang en-aut-mei=Dengli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OusakaDaiki en-aut-sei=Ousaka en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OozawaSusumu en-aut-sei=Oozawa en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KasaharaShingo en-aut-sei=Kasahara en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Translational Research, Center for Innovative Clinical Medicine, Medical Development Field, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Medical Technology, Faculty of Science, Okayama University of Science kn-affil= affil-num=7 en-affil=Division of Medical Safety Management, Safety Management Facility, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Cardiovascular Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Translational Research and Drug Development, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=thoracoabdominal aortic aneurysm kn-keyword=thoracoabdominal aortic aneurysm en-keyword=spinal cord ischemia–reperfusion injury kn-keyword=spinal cord ischemia–reperfusion injury en-keyword=high mobility group box 1 kn-keyword=high mobility group box 1 en-keyword=neuroprotection kn-keyword=neuroprotection en-keyword=blood–spinal cord barrier kn-keyword=blood–spinal cord barrier en-keyword=aortic surgery kn-keyword=aortic surgery END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=305 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250818 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Precise stratification of prognosis in pancreatic ductal adenocarcinoma patients based on pre- and postoperative genomic information en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate among all cancers; hence, multidisciplinary treatment is essential for patients with PDAC. Although the resectability status, tumour marker, KRAS circulating tumour DNA (mutKRAS-ctDNA) mutations, and GATA binding 6 (GATA6) expression status are promising prognostic biomarkers, their effective integration before and after surgery remains unclear.
Methods In this retrospective cohort study, patients with PDAC who had undergone radical resection were enrolled, and pre- and postoperative independent factors associated with poor prognosis were identified using Cox hazard modelling. Risk stratification systems were developed using the identified prognostic factors and investigated for the ability to predict prognosis.
Results A total of 91 patients with PDAC were included (median follow-up duration, 28 months). Borderline resectable or locally advanced cancer at diagnosis, elevated carbohydrate antigen 19–9 (CA19-9) level, and mutKRAS-ctDNA-positive status were identified as independent preoperative factors associated with poor prognosis. The postoperative factors significantly associated with shorter overall survival were low GATA6 expression, elevated CA19-9 level, and mutKRAS-ctDNA-positive status. Finally, the preoperative and postoperative risk scoring systems developed using Cox modelling hazard ratio values could significantly stratify prognosis after curative resection for PDAC.
Conclusion A risk stratification system based on liquid biopsy, specialised for each phase (pre- and post-surgery), has been proven to be a useful, simple, and practical prognostic prediction clinical tool to determine the optimal multidisciplinary treatment protocol for PDAC. en-copyright= kn-copyright= en-aut-name=MiyamotoKokichi en-aut-sei=Miyamoto en-aut-mei=Kokichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaRyuichi en-aut-sei=Yoshida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=YoshidaKazuhiro en-aut-sei=Yoshida en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=11 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=12 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=13 ORCID= en-aut-name=NishiyamaTakeyoshi en-aut-sei=Nishiyama en-aut-mei=Takeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 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=18 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=19 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=20 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=21 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science 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 Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Biomedical Informatics, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=20 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=21 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Pancreatic ductal adenocarcinoma kn-keyword=Pancreatic ductal adenocarcinoma en-keyword=Risk stratification kn-keyword=Risk stratification en-keyword=Prognosis kn-keyword=Prognosis en-keyword=Tumour marker kn-keyword=Tumour marker en-keyword=KRAS kn-keyword=KRAS END start-ver=1.4 cd-journal=joma no-vol=65 cd-vols= no-issue=9 article-no= start-page=396 end-page=406 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250915 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real-world Experience of Embolization for Intracranial Tumors in Japan: Analysis of 2,756 Cases from Japanese Registry of NeuroEndovascular Therapy 4 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Embolization of intracranial tumors is predominantly performed in Japan, primarily before neurosurgical resection. The Japanese Registry of NeuroEndovascular Therapy (JR-NET) Study Group, established in 2005, aims to clarify the factors influencing the outcomes of neuroendovascular treatment. Japanese Registry of NeuroEndovascular Therapy 4 is a nationwide, multicenter retrospective observational study that evaluates real-world data on intracranial tumor embolization in Japan. Japanese Registry of NeuroEndovascular Therapy 4 is based on data collected from 166 neurosurgical centers in Japan between January 2015 and December 2019. Of 63,230 patients, 2,664 (4.2%) with intracranial tumors underwent embolization. The primary endpoint was the proportion of patients with a modified Rankin scale (mRS) score of 0-2 at 30 days post-procedure. Secondary endpoints included procedure-related complications. Among the 2,664 patients, 61 records lacked sufficient data, leaving 2,603 patients (1,612 females, median age: 61 years [interquartile range 51-71]). The proportion of patients with mRS scores ≤2 at 30 days after the procedure was 86.9%. The overall incidence of procedure-related complications was 4.8%, with 1.8% hemorrhagic, 2.0% ischemic, and 1.0% classified as other complications. In the multivariate analysis, general anesthesia and embolization of vessels other than the external carotid artery were identified as risk factors for the development of complications. Meningioma cases had a complication rate of 4.3%, with major complications occurring in 3.5%. Hemangioblastoma cases had a 14.9% complication rate, with major complications at 9.9%. Japanese Registry of NeuroEndovascular Therapy 4 provides comprehensive real-world data on intracranial tumor embolization in Japan, identifying risk factors to inform and improve the safe practice of intracranial tumor embolization in neuroendovascular therapy. en-copyright= kn-copyright= en-aut-name=HARUMAJun en-aut-sei=HARUMA en-aut-mei=Jun 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=HISHIKAWATomohito en-aut-sei=HISHIKAWA en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SOUTOMEYuta en-aut-sei=SOUTOME en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EBISUDANIYuki en-aut-sei=EBISUDANI en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KIMURARyu en-aut-sei=KIMURA en-aut-mei=Ryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EDAKIHisanori en-aut-sei=EDAKI en-aut-mei=Hisanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KAWAKAMIMasato en-aut-sei=KAWAKAMI en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MURAISatoshi en-aut-sei=MURAI en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HIRAMATSUMasafumi en-aut-sei=HIRAMATSU en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TANAKAShota en-aut-sei=TANAKA en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SATOWTetsu en-aut-sei=SATOW en-aut-mei=Tetsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IIHARAKoji en-aut-sei=IIHARA en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 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=15 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=16 ORCID= en-aut-name=SAKAIChiaki en-aut-sei=SAKAI en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YOSHIMURAShinichi en-aut-sei=YOSHIMURA en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SAKAINobuyuki en-aut-sei=SAKAI en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=Japanese Registry of Neuroendovascular Therapy (JR-NET) Investigators en-aut-sei=Japanese Registry of Neuroendovascular Therapy (JR-NET) Investigators en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurosurgery, Kawasaki Medical School kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neurosurgery, Kawasaki Medical School kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurosurgery, Kindai University kn-affil= affil-num=13 en-affil=Department of Neurosurgery, National Cerebral and Cardiovascular Center kn-affil= affil-num=14 en-affil=Department of Neurosurgery, National Cerebral and Cardiovascular Center kn-affil= affil-num=15 en-affil=Department of Neurosurgery, Juntendo University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Neurosurgery, Institute of Medicine, University of Tsukuba kn-affil= affil-num=17 en-affil=Department of Neurosurgery, Kyoto University kn-affil= affil-num=18 en-affil=Department of Neurosurgery, Hyogo Medical University kn-affil= affil-num=19 en-affil=Department of Neurological Surgery, Shimizu Hospital kn-affil= affil-num=20 en-affil= kn-affil= en-keyword=complication kn-keyword=complication en-keyword=intracranial tumor kn-keyword=intracranial tumor en-keyword=embolization kn-keyword=embolization en-keyword=Japanese registry kn-keyword=Japanese registry 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=20250905 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Double-blind randomized noninferiority study of the effect of pharyngeal lidocaine anesthesia on EUS en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and objectives: EUS is typically performed under sedation, often with concomitant analgesics to reduce pain. Traditionally used pharyngeal anesthesia, commonly with lidocaine, may cause pharyngeal discomfort and allergic reactions. This study investigated whether lidocaine-based pharyngeal anesthesia is necessary for EUS under sedation with analgesics.
Methods: A double-blind, randomized, noninferiority study was conducted on EUS cases that met the selection criteria. Patients were randomly assigned to receive either 5 sprays of 8% lidocaine (lidocaine group: LG) or saline spray (placebo group: PG) as endoscopy pretreatment. The primary outcome was EUS tolerability, analyzed separately for endoscopists and patients, with a noninferiority margin set at 15%. Secondary outcomes included endoscopist and patient satisfaction, midazolam/pethidine doses, number of gag events, number of esophageal insertion attempts, use of sedative/analgesic antagonists, interruptions due to body movements, throat symptoms after endoscopy, and sedation-related adverse events.
Results: Favorable tolerance was 85% in LG and 88% for PG among endoscopists (percent difference: 3.0 [95% confidence interval, −6.6 to 12.6]) and 90% in LG and 91% in PG among patients (percent difference, 0.94 [95% confidence interval, −7.5 to 9.4]). Both groups exceeded the noninferiority margin (P = 0.0002 for endoscopists and patients). Patient satisfaction was significantly higher in PG (P = 0.0080), but no intergroup differences were found in other secondary outcomes.
Conclusions: PG was noninferior to LG for pharyngeal anesthesia during EUS with sedation and analgesics. These results suggest that pharyngeal anesthesia with lidocaine can be omitted when performing EUS under sedation with concomitant analgesics. Omitting pharyngeal anesthesia with lidocaine may prevent discomfort and complications caused by pharyngeal anesthesia, shorten examination times, and reduce medical costs. en-copyright= kn-copyright= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaKei en-aut-sei=Harada en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HattoriNao en-aut-sei=Hattori en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ObataTaisuke en-aut-sei=Obata en-aut-mei=Taisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsutsumiKoichiro en-aut-sei=Tsutsumi en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=13 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=EUS kn-keyword=EUS en-keyword=Lidocaine kn-keyword=Lidocaine en-keyword=Tolerance kn-keyword=Tolerance END start-ver=1.4 cd-journal=joma no-vol=34 cd-vols= no-issue=2 article-no= start-page=67 end-page=73 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=Depletion of Lysyl Oxidase-Like 4 (LOXL4) Attenuates Colony Formation in vitro and Collagen Deposition in vivo Breast Cancer Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Lysyl oxidase (LOX) family proteins have recently become a topic in cancer progression. Our recent study found a high expression of LOX-like 4 (LOXL4) in MDA-MB-231 cells. Objective: To reveal the impact of depleted LOXL4 in both in vitro and in vivo breast cancer models from a histological perspective. Material and Method: Endogenous LOXL4 was depleted using the CRISPR/Cas9 on MDA-MB-231 parental cells. Based on the LOXL4 protein expression, the clone was determined for the next experiment, thus generating MDA-MB-231 LOXL4 KO. Cell assay was conducted using colony formation assay (n=3) followed by crystal violet staining. The indicated cells were inoculated orthotopically to female BALB/c nude mice (n=5). At the end of the experiment, tumors were isolated, fixed, and prepared for Masson Trichrome staining. Result: CRISPR/Cas9 completely depleted LOXL4 expression on clone number #2-22. Depletion of LOXL4 reduced the colony size formed by MDA-MB-231 cells. MDA-MB-231 LOXL4 KO #2-22 derived tumors showed depressed tumor volume compared to the parental group. Reduced collagen was also observed from the Masson Trichrome staining (p<0.001). Conclusion: Depletion of LOXL4 downregulates the growth of MDA-MB-231 cells in vitro and collagen deposition in vivo. en-copyright= kn-copyright= en-aut-name=Ni Luh Gede Yoni Komalasari en-aut-sei=Ni Luh Gede Yoni Komalasari en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=I Gde Haryo Ganesha en-aut-sei=I Gde Haryo Ganesha en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=I Gusti Nyoman Sri Wiryawan en-aut-sei=I Gusti Nyoman Sri Wiryawan en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Cell Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Histology, Faculty of Medicine, Udayana University kn-affil= affil-num=3 en-affil=Department of Histology, Faculty of Medicine, Udayana University kn-affil= affil-num=4 en-affil=Department of Cell Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Cell Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University kn-affil= en-keyword=Good health kn-keyword=Good health en-keyword=Lysyl oxidase kn-keyword=Lysyl oxidase en-keyword=Extracellular matrix kn-keyword=Extracellular matrix 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=20250903 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Vendor‐Agnostic Vision Transformer‐Based Artificial Intelligence for Peroral Cholangioscopy: Diagnostic Performance in Biliary Strictures Compared With Convolutional Neural Networks and Endoscopists en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Accurate diagnosis of biliary strictures remains challenging. This study aimed to develop an artificial intelligence (AI) system for peroral cholangioscopy (POCS) using a Vision Transformer (ViT) architecture and to evaluate its performance compared to different vendor devices, conventional convolutional neural networks (CNNs), and endoscopists.
Methods: We retrospectively analyzed 125 patients with indeterminate biliary strictures who underwent POCS between 2012 and 2024. AI models including the ViT architecture and two established CNN architectures were developed using images from CHF-B260 or B290 (CHF group; Olympus Medical) and SpyScope DS or DS II (Spy group; Boston Scientific) systems via a patient-level, 3-fold cross-validation. For a direct comparison against endoscopists, a balanced 440-image test set, containing an equal number of images from each vendor, was used for a blinded evaluation.
Results: The 3-fold cross-validation on the entire 2062-image dataset yielded a robust accuracy of 83.9% (95% confidence interval (CI), 80.9–86.7) for the ViT model. The model's accuracy was consistent between CHF (82.7%) and Spy (86.8%, p = 0.198) groups, and its performance was comparable to the evaluated conventional CNNs. On the 440-image test set, the ViT's accuracy of 78.4% (95% CI, 72.5–83.8) was comparable to that of expert endoscopists (82.0%, p = 0.148) and non-experts (73.0%, p = 0.066), with no statistically significant differences observed.
Conclusions: The novel ViT-based AI model demonstrated high vendor-agnostic diagnostic accuracy across multiple POCS systems, achieving performance comparable to conventional CNNs and endoscopists evaluated in this study. en-copyright= kn-copyright= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomiyaMasahiro en-aut-sei=Tomiya en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanimotoTakayoshi en-aut-sei=Tanimoto en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhtoAkimitsu en-aut-sei=Ohto en-aut-mei=Akimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkiKentaro en-aut-sei=Oki en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KajitaniSatoshi en-aut-sei=Kajitani en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KikuchiTatsuya en-aut-sei=Kikuchi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=11 ORCID= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TsutsumiKoichiro en-aut-sei=Tsutsumi en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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=16 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=Healthcare Solutions Division, Ryobi Systems Co., Ltd kn-affil= affil-num=4 en-affil=Healthcare Solutions Division, Ryobi Systems Co., Ltd kn-affil= affil-num=5 en-affil=Healthcare Solutions Division, Ryobi Systems Co., Ltd kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=bile duct neoplasms kn-keyword=bile duct neoplasms en-keyword=cholangioscopy kn-keyword=cholangioscopy en-keyword=computer-assisted diagnosis kn-keyword=computer-assisted diagnosis en-keyword=vision transformer kn-keyword=vision transformer END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=113544 end-page=113556 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Optimized Ensemble Deep Learning for Real-Time Intrusion Detection on Resource-Constrained Raspberry Pi Devices en-subtitle= kn-subtitle= en-abstract= kn-abstract=The rapid growth of Internet of Things (IoT) networks has increased security risks, making it essential to have effective Intrusion Detection Systems (IDS) for real-time threat detection. Deep learning techniques offer promising solutions for such detection due to their superior complex pattern recognition and anomaly detection capabilities in large datasets. This paper proposes an optimized ensemble-based IDS designed specifically for efficient deployment on edge hardware. However, deploying such computationally intensive models on resource-limited edge devices remains a significant challenge due to model size and computational overhead on devices with limited processing capabilities. Building upon our previously developed stacked Long Short-Term Memory (LSTM) model integrated with ANOVA feature selection, we optimize it by integrating dual-stage model compression: pruning and quantization to create a lightweight model suitable for real-time inference on Raspberry Pi devices. To evaluate the system under realistic conditions, we combined with a Kafka-based testbed to simulate dynamic IoT environments with variable traffic loads, delays, and multiple simultaneous attack sources. This enables the assessment of detection performance under varying traffic volumes, latency, and overlapping attack scenarios. The proposed system maintains high detection performance with accuracy of 97.3% across all test scenarios, while efficiently leveraging multi-core processing with peak CPU usage reaching 111.8%. These results demonstrate the system’s practical viability for real-time IoT security at the edge. en-copyright= kn-copyright= 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=1 ORCID= en-aut-name=HudaSamsul en-aut-sei=Huda en-aut-mei=Samsul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NguyenTuy Tan en-aut-sei=Nguyen en-aut-mei=Tuy Tan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KoderaYuta en-aut-sei=Kodera en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=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=Interdisciplinary Education and Research Field, Okayama University kn-affil= affil-num=3 en-affil=School of Informatics, Computing, and Cyber Systems, Northern Arizona 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=Internet of things kn-keyword=Internet of things en-keyword=intrusion detection system kn-keyword=intrusion detection system en-keyword=stacked lstm kn-keyword=stacked lstm en-keyword=pruning model kn-keyword=pruning model en-keyword=optimizing model kn-keyword=optimizing model en-keyword=quantization model kn-keyword=quantization model en-keyword=raspberry pi kn-keyword=raspberry pi en-keyword=real-time detection kn-keyword=real-time detection en-keyword=apache kafka kn-keyword=apache kafka END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=89003 end-page=89024 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250519 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Security in Post-Quantum Era: A Comprehensive Survey on Lattice-Based Algorithms en-subtitle= kn-subtitle= en-abstract= kn-abstract=Lattice-based post-quantum cryptography (PQC) has attracted significant attention as a promising solution to the security challenges posed by quantum computing. Unlike traditional cryptographic algorithms, lattice-based schemes are expected to remain secure even in the presence of quantum attacks, making them essential for securing future data. Despite their strong theoretical foundations, lattice-based schemes face several practical challenges, particularly in optimizing performance and scalability for real-world applications. This survey provides a novel taxonomy that categorizes lattice-based PQC designs, with an emphasis on computational paradigms and security considerations. We systematically evaluate lattice-based PQC implementations across both software platforms, including central processing units and graphics processing units, as well as hardware platforms like field-programmable gate arrays and application-specific integrated circuits, highlighting their strengths and limitations. In addition, we explore the practical applications of lattice-based cryptography in fields such as secure communication, critical infrastructure, privacy-preserving data analytics, artificial intelligence, and trust and authentication systems. By offering a comprehensive overview of the current state of lattice-based PQC, this survey aims to provide valuable insights into the ongoing advancements and future research directions in the field as we transition to a post-quantum era. en-copyright= kn-copyright= en-aut-name=NguyenHien en-aut-sei=Nguyen en-aut-mei=Hien kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HudaSamsul en-aut-sei=Huda en-aut-mei=Samsul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=NguyenTuy Tan en-aut-sei=Nguyen en-aut-mei=Tuy Tan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=School of Informatics, Computing, and Cyber Systems, Northern Arizona University kn-affil= affil-num=2 en-affil=Interdisciplinary Education and Research Field, 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=School of Informatics, Computing, and Cyber Systems, Northern Arizona University kn-affil= en-keyword=Post-quantum cryptography kn-keyword=Post-quantum cryptography en-keyword=lattice-based cryptography kn-keyword=lattice-based cryptography en-keyword=number theoretic transform kn-keyword=number theoretic transform en-keyword=hardware and software implementation kn-keyword=hardware and software implementation END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=8 article-no= start-page=e70325 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cardiotoxicity Assessment of EGFR Tyrosine Kinase Inhibitors Using Human iPS Cell‐Derived Cardiomyocytes and FDA Adverse Events Reporting System en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent advances in the development of anti-cancer drugs have contributed to prolonged survival of cancer patients. In contrast, drug-induced cardiotoxicity, particularly cardiac contractile dysfunction, is of growing concern in cancer treatment. Therefore, it is important to understand the risks of anti-cancer drug-induced cardiac contractile dysfunction in drug development. We have previously developed image-based motion analysis using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to assess the effect of drugs on contractility. However, the utility and predictive potential of image-based motion analysis using hiPSC-CMs for anti-cancer drug-induced cardiac contractile dysfunction have not been well understood. Here we focused on epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and investigated the correlation between the hiPSC-CMs data and clinical signals of adverse events related to cardiac contractile dysfunction. We examined the effects of the four EGFR-TKIs, osimertinib, gefitinib, afatinib, and erlotinib, on the contractility of hiPSC-CMs using image-based motion analysis. We found that osimertinib decreased contraction velocity and deformation distance in a dose- and time-dependent manner, whereas gefitinib, afatinib, and erlotinib had little effect on these parameters. Next, we examined the real-world data of the EGFR-TKIs using FDA Adverse Event Reporting System (FAERS; JAPIC AERS). Only osimertinib showed significant clinical signals of adverse events related to cardiac contractile dysfunction. These data suggest that hiPSC-CM data correlate with clinical signals in FAERS analysis for four EGFR-TKIs. Thus, image-based motion analysis using hiPSC-CMs can be a useful platform for predicting the risk of anti-cancer drug-induced cardiac contractile dysfunction in patients. en-copyright= kn-copyright= en-aut-name=YanagidaShota en-aut-sei=Yanagida en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawagishiHiroyuki en-aut-sei=Kawagishi en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SaitoMitsuo en-aut-sei=Saito en-aut-mei=Mitsuo 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=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KandaYasunari en-aut-sei=Kanda en-aut-mei=Yasunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Division of Pharmacology, National Institute of Health Sciences (NIHS) kn-affil= affil-num=2 en-affil=Division of Pharmacology, National Institute of Health Sciences (NIHS) kn-affil= affil-num=3 en-affil=Japan Pharmaceutical Information Center (JAPIC) kn-affil= affil-num=4 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Division of Pharmacology, National Institute of Health Sciences (NIHS) kn-affil= en-keyword=cardiomyocytes kn-keyword=cardiomyocytes en-keyword=cardiotoxicity kn-keyword=cardiotoxicity en-keyword=contractility kn-keyword=contractility en-keyword=EGFR-tyrosine kinase inhibitor kn-keyword=EGFR-tyrosine kinase inhibitor en-keyword=FAERS kn-keyword=FAERS en-keyword=human iPS cell kn-keyword=human iPS cell END start-ver=1.4 cd-journal=joma no-vol=188 cd-vols= no-issue= article-no= start-page=118137 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=Unravelling the cardioprotective effects of calcitriol in Sunitinib-induced toxicity: A comprehensive in silico and in vitro study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sunitinib (SUN), a drug used to treat advanced renal cell carcinoma and other cancers, causes cardiotoxicity. This study aimed to identify a potential drug candidate to counteract SUN-induced cardiotoxicity. We analysed real-world data from adverse event report databases of existing clinically approved drugs to identify potential candidates. Through in silico analyses and in vitro experiments, the mechanisms of action were determined. The study identified calcitriol (CTL), an active form of vitamin D, as a promising candidate against SUN-induced cardiotoxicity. In H9c2 cells, SUN decreased cell viability significantly, whereas CTL mitigated this effect significantly. The SUN-treated group exhibited increased autophagy in H9c2 cells, which was reduced significantly in the CTL group. Bioinformatics analysis using Ingenuity Pathway Analysis revealed the mechanistic target of rapamycin (mTOR) as a common factor between autophagy and CTL. Notably, rapamycin, an mTOR inhibitor, nullified the effects of CTL on cell viability and autophagy. Furthermore, SUN treatment led to significant reductions in cardiomyocyte diameters and increases in their widths, changes that were inhibited by CTL. SUN also induced morphological changes in surviving H9c2 cells, causing them to adopt a rounded shape, whereas CTL improved their morphology to resemble the elongated shape of the control group. In conclusion, the findings of the present study suggest that CTL has the potential to prevent SUN-induced cardiomyocyte damage through autophagy, particularly via mTOR-mediated pathways. The findings indicate that CTL could serve as an effective prophylactic agent against SUN-induced cardiotoxicity, offering a promising avenue for further research and potential clinical applications. en-copyright= kn-copyright= en-aut-name=SakamotoYoshika en-aut-sei=Sakamoto en-aut-mei=Yoshika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=TomochikaNanami en-aut-sei=Tomochika en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakawaWakana en-aut-sei=Murakawa en-aut-mei=Wakana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=9 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=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=Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=2 en-affil=Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=3 en-affil=Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=4 en-affil=Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=5 en-affil=Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=6 en-affil=Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=7 en-affil=Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=8 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=10 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences kn-affil= en-keyword=Sunitinib kn-keyword=Sunitinib en-keyword=Advanced renal cell carcinoma kn-keyword=Advanced renal cell carcinoma en-keyword=Cardiotoxicity kn-keyword=Cardiotoxicity en-keyword=Calcitriol kn-keyword=Calcitriol en-keyword=Autophagy kn-keyword=Autophagy en-keyword=MTOR kn-keyword=MTOR END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=40 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250428 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Time dependent predictors of cardiac inflammatory adverse events in cancer patients receiving immune checkpoint inhibitors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Cardio-inflammatory immune related adverse events (irAEs) while receiving immune checkpoint inhibitor (ICI) therapy are particularly consequential due to their associations with poorer treatment outcomes. Evaluation of predictive factors of these serious irAEs with a time dependent approach allows better understanding of patients most at risk.
Objective: To identify different elements of patient data that are significant predictors of early and late-onset or delayed cardio-inflammatory irAEs through various predictive modeling strategies.
Methods: A cohort of patients receiving ICI therapy from January 1, 2010 to May 1, 2022 was identified from TriNetX meeting inclusion/exclusion criteria. Patient data collected included occurrence of early and later cardio-inflammatory irAEs, patient survival time, patient demographic information, ICI therapies, comorbidities, and medication histories. Predictive and statistical modeling approaches identified unique risk factors for early and later developing cardio-inflammatory irAEs.
Results: A cohort of 66,068 patients on ICI therapy were identified in the TriNetX platform; 193 (0.30%) experienced early cardio-inflammatory irAEs and 175 (0.26%) experienced later cardio-inflammatory irAEs. Significant predictors for early irAEs included: anti-PD-1 therapy at index, combination ICI therapy at index, and history of peripheral vascular disease. Significant predictors for later irAEs included: a history of myocarditis and/or pericarditis, cerebrovascular disease, and history of non-steroidal anti-inflammatory medication use.
Conclusions: Cardio-inflammatory irAEs can be divided into clinically meaningful categories of early and late based on time since initiation of ICI therapy. Considering distinct risk factors for early-onset and late-onset events may allow for more effective patient monitoring and risk assessment. en-copyright= kn-copyright= en-aut-name=SayerMichael en-aut-sei=Sayer en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=LeeBenjamin J. en-aut-sei=Lee en-aut-mei=Benjamin J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DohJean en-aut-sei=Doh en-aut-mei=Jean kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=PatelPranav M. en-aut-sei=Patel en-aut-mei=Pranav M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OzakiAya F. en-aut-sei=Ozaki en-aut-mei=Aya F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= affil-num=2 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=3 en-affil=Division of Hematology and Oncology, University of California kn-affil= affil-num=4 en-affil=Department of Pharmacy, University of California Irvine Health kn-affil= affil-num=5 en-affil=Department of Pharmacy, University of California Irvine Health kn-affil= affil-num=6 en-affil=Division of Cardiology, Department of Medicine, University of California kn-affil= affil-num=7 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=8 en-affil=School of Pharmacy & Pharmaceutical Sciences, University of California kn-affil= en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors en-keyword=Immune-Related adverse events kn-keyword=Immune-Related adverse events en-keyword=Myocarditis kn-keyword=Myocarditis en-keyword=Pericarditis kn-keyword=Pericarditis en-keyword=Predictive modeling kn-keyword=Predictive modeling en-keyword=TriNetx kn-keyword=TriNetx END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250701 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bioengineered chondrocyte-products from human induced pluripotent stem cells are useful for repairing articular cartilage injury in minipig model en-subtitle= kn-subtitle= en-abstract= kn-abstract=The capacity of articular cartilage for self-repair is limited. Therefore, wide-ranging cartilage damage rarely resolves spontaneously, leading to the development of osteoarthritis. Previously, we developed human-induced pluripotent stem cell (hiPSC)-derived expandable human limb-bud-like mesenchymal (ExpLBM) cells with stable expansion and high chondrogenic capacity. In this study, various forms of articular cartilage-like tissue were fabricated using ExpLBM technology and evaluated to examine their potential as biomaterials. ExpLBM cells derived from hiPSCs were used to produce particle-like cartilage tissue and plate-like cartilage tissue. The cartilaginous particles and cartilaginous plates were transplanted into a minipig osteochondral defect model, and cartilage engraftment was histologically evaluated. For both transplanted cartilaginous particles and cartilaginous plates, good Safranin O staining and integration with the surrounding tissue were observed. Cartilaginous particles and cartilaginous plates made using hiPSCs-derived ExpLBM cells are effective for the regeneration of cartilage after injury. en-copyright= kn-copyright= en-aut-name=TakihiraShota en-aut-sei=Takihira en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakaoTomoka en-aut-sei=Takao en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujisawaYuki en-aut-sei=Fujisawa en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamadaDaisuke en-aut-sei=Yamada en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HanakiShojiro en-aut-sei=Hanaki en-aut-mei=Shojiro 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=OtakeShigeo en-aut-sei=Otake en-aut-mei=Shigeo 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=YamadaKazuki en-aut-sei=Yamada en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyazawaShinichi en-aut-sei=Miyazawa en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakaradaTakeshi en-aut-sei=Takarada en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=11 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=5 article-no= start-page=1302 end-page=1309 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250718 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=X-ray fluorescence holography under high-pressure conditions en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study reports the first application of X-ray fluorescence holography (XFH) under high-pressure conditions. We integrated XFH with a diamond anvil cell to investigate the local structure around Sr atoms in single-crystal SrTiO3 under high pressure. By utilizing nano-polycrystalline diamond anvils and a yttrium filter, we effectively eliminated significant background noise from both the anvils and the gasket. This optimized experimental configuration enabled the measurement of Sr Kα holograms of the SrTiO3 sample at pressures up to 13.3 GPa. The variation of lattice constants with pressure was calculated by the shifts of Kossel lines, and real-space images of the atomic structures were reconstructed from the Sr Kα holograms at different pressures. This work successfully demonstrates the feasibility of employing XFH under high-pressure conditions as a novel method for visualizing pressure-induced changes in the three-dimensional local structure around the specified element. en-copyright= kn-copyright= en-aut-name=ZhanXinhui en-aut-sei=Zhan en-aut-mei=Xinhui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshimatsuNaoki en-aut-sei=Ishimatsu en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraKoji en-aut-sei=Kimura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HappoNaohisa en-aut-sei=Happo en-aut-mei=Naohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SekharHalubai en-aut-sei=Sekhar en-aut-mei=Halubai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatoTomoko en-aut-sei=Sato en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakajimaNobuo en-aut-sei=Nakajima en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawamuraNaomi en-aut-sei=Kawamura en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HigashiKotaro en-aut-sei=Higashi en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SekizawaOki en-aut-sei=Sekizawa en-aut-mei=Oki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KadobayashiHirokazu en-aut-sei=Kadobayashi en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=EguchiRitsuko en-aut-sei=Eguchi en-aut-mei=Ritsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KubozonoYoshihiro en-aut-sei=Kubozono en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TajiriHiroo en-aut-sei=Tajiri en-aut-mei=Hiroo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HosokawaShinya en-aut-sei=Hosokawa en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MatsushitaTomohiro en-aut-sei=Matsushita en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ShinmeiToru en-aut-sei=Shinmei en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IrifuneTetsuo en-aut-sei=Irifune en-aut-mei=Tetsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HayashiKoichi en-aut-sei=Hayashi en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Graduate School of Advanced Science and Engineering, Hiroshima University kn-affil= affil-num=2 en-affil=Geodynamics Research Center, PIAS, Ehime University kn-affil= affil-num=3 en-affil=Department of Physical Science and Engineering, Nagoya Institute of Technology kn-affil= affil-num=4 en-affil=Graduate School of Information Sciences, Hiroshima City University kn-affil= affil-num=5 en-affil=Institute of Industrial Nanomaterials, Kumamoto University kn-affil= affil-num=6 en-affil=Institute of Materials Structure Science, High Energy Accelerator Research Organization, KEK kn-affil= affil-num=7 en-affil=Graduate School of Advanced Science and Engineering, Hiroshima University kn-affil= affil-num=8 en-affil=Japan Synchrotron Radiation Research Institute, SPring-8 kn-affil= affil-num=9 en-affil=Japan Synchrotron Radiation Research Institute, SPring-8 kn-affil= affil-num=10 en-affil=Japan Synchrotron Radiation Research Institute, SPring-8 kn-affil= affil-num=11 en-affil=Japan Synchrotron Radiation Research Institute, SPring-8 kn-affil= affil-num=12 en-affil=Graduate School of Science, University of Hyogo kn-affil= affil-num=13 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=14 en-affil=Japan Synchrotron Radiation Research Institute, SPring-8 kn-affil= affil-num=15 en-affil=Faculty of Materials for Energy, Shimane University kn-affil= affil-num=16 en-affil=Graduate School of Science and Technology, Nara Institute of Science and Technology kn-affil= affil-num=17 en-affil=Geodynamics Research Center, PIAS, Ehime University kn-affil= affil-num=18 en-affil=Geodynamics Research Center, PIAS, Ehime University kn-affil= affil-num=19 en-affil=Department of Physical Science and Engineering, Nagoya Institute of Technology kn-affil= en-keyword=X-ray fluorescence holography kn-keyword=X-ray fluorescence holography en-keyword=high pressure kn-keyword=high pressure en-keyword=SrTiO3 kn-keyword=SrTiO3 END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=4 article-no= start-page=139 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250402 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An Implementation of Creep Test Assisting System with Dial Gauge Needle Reading and Smart Lighting Function for Laboratory Automation en-subtitle= kn-subtitle= en-abstract= kn-abstract=For decades, analog dial gauges have been essential for measuring and monitoring data at various industrial instruments including production machines and laboratory equipment. Among them, we focus on the instrument for creep test in a mechanical engineering laboratory, which evaluates material strength under sustained stress. Manual reading of gauges imposes significant labor demands, especially in long-duration tests. This burden further increases under low-lighting environments, where poor visibility can lead to misreading data points, potentially compromising the accuracy of test results. In this paper, to address the challenges, we implement a creep test assisting system that possesses the following features: (1) to save the installation cost, a web camera and Raspberry Pi are employed to capture images of the dial gauge and automate the needle reading by image processing in real time, (2) to ensure reliability under low-lighting environments, a smart lighting mechanism is integrated to turn on a supplementary light when the dial gauge is not clearly visible, and (3) to allow a user to stay in a distant place from the instrument during a creep test, material break is detected and the corresponding message is notified to a laboratory staff using LINE automatically. For evaluations, we install the implemented system into a material strength measuring instrument at Okayama University, Japan, and confirm the effectiveness and accuracy through conducting experiments under various lighting conditions. 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=FangShihao en-aut-sei=Fang en-aut-mei=Shihao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Noprianto en-aut-sei=Noprianto en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkayasuMitsuhiro en-aut-sei=Okayasu en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=PuspitaningayuPradini en-aut-sei=Puspitaningayu en-aut-mei=Pradini kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil= Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil= Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil= Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil= Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil= Department of Electrical Engineering, Universitas Negeri Surabaya kn-affil= en-keyword=creep test kn-keyword=creep test en-keyword=Raspberry Pi kn-keyword=Raspberry Pi en-keyword=dial gauge kn-keyword=dial gauge en-keyword=needle reading kn-keyword=needle reading en-keyword=smart lighting kn-keyword=smart lighting END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=4 article-no= start-page=401 end-page=409 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High-Definition Topographic Archiving and Educational Applications in Regions Affected by the 2024 Noto Peninsula Earthquake en-subtitle= kn-subtitle= en-abstract= kn-abstract=The 2024 Noto Peninsula earthquake (Mw 7.5) caused extensive damage in Ishikawa Prefecture, Japan, and surrounding areas, with considerable coastal uplift and tsunami flooding. Past 100 years’ records show no earthquake above Mw 7.0 in the Noto Peninsula, so for everyone alive today, this event is truly without precedent. Therefore, we aimed to support disaster prevention education by developing teaching materials using unmanned aerial vehicles (UAVs) based on digitally archived topographic changes. High-definition topographic data collected from multiple UAV surveys were processed into digital and analog formats, including 3D models, spherical panorama images, and 3D printings. These materials were designed to provide detailed and intuitive representations of post-disaster landforms and were used as educational tools in schools. The learning materials were introduced during a workshop for disaster-affected teachers, featuring hands-on activities to help participants familiarize themselves with the materials, and explore their integration into geography and science classes. Feedback from participants indicated that these tools were highly effective in enhancing classroom learning. The results of this study are expected to contribute to preserving disaster records while enhancing disaster awareness in educational settings and local communities. en-copyright= kn-copyright= en-aut-name=OguraTakuro en-aut-sei=Ogura en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamauchiHiroyuki en-aut-sei=Yamauchi en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AokiTatsuto en-aut-sei=Aoki en-aut-mei=Tatsuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MattaNobuhisa en-aut-sei=Matta en-aut-mei=Nobuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IizukaKotaro en-aut-sei=Iizuka en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwasaYoshiya en-aut-sei=Iwasa en-aut-mei=Yoshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiTakayuki en-aut-sei=Takahashi en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HayashiKiyomi en-aut-sei=Hayashi en-aut-mei=Kiyomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HattanjiTsuyoshi en-aut-sei=Hattanji en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OguchiTakashi en-aut-sei=Oguchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Graduate School of Education, Hyogo University of Teacher Education kn-affil= affil-num=2 en-affil=Art Research Center, Ritsumeikan University kn-affil= affil-num=3 en-affil=Faculty of Regional Development Studies, Kanazawa University kn-affil= affil-num=4 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=5 en-affil=Center for Spatial Information Science, The University of Tokyo kn-affil= affil-num=6 en-affil=Faculty of Education, University of Teacher Education Fukuoka kn-affil= affil-num=7 en-affil=International Research Institute of Disaster Science, Tohoku University kn-affil= affil-num=8 en-affil=Faculty of Regional Development Studies, Kanazawa University kn-affil= affil-num=9 en-affil=Institute of Life and Environmental Sciences, University of Tsukuba kn-affil= affil-num=10 en-affil=Center for Spatial Information Science, The University of Tokyo kn-affil= en-keyword=disaster risk-reduction education kn-keyword=disaster risk-reduction education en-keyword=uplift area kn-keyword=uplift area en-keyword=UAV kn-keyword=UAV en-keyword=3D printing kn-keyword=3D printing END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Asymptomatic intracranial vascular lesions and cognitive function in a general population of Japanese men: Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Intracranial subclinical vessel diseases are considered important indicators of cognitive impairment. However, a comprehensive assessment of various types of vessel disease, particularly in Asian populations, is lacking. We aimed to compare multiple types of intracranial vessel disease in association with cognitive function among a community-based Japanese male population. Methods: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) randomly recruited and examined a community-based cohort of Japanese men from Shiga, Japan. We analyzed those who underwent the Cognitive Abilities Screening Instrument (CASI) assessment and cranial magnetic resonance imaging/angiogram (MRI/MRA) in 2010–2015. Using MRI/MRA, we assessed lacunar infarction, microbleeds, periventricular hyperintensity (PVH), deep subcortical white matter hyperintensity (DSWMH), and intracranial artery stenosis (ICAS). We divided these subclinical cerebrovascular diseases (SCDs) into three categories according to severity. Using linear regression, we calculated the CASI score according to the grade of each vessel disease, adjusted for age and years of education. Results: In the adjusted models, CASI scores were significantly associated with both PVH and DSWMH. Specifically, multivariable-adjusted CASI scores declined across increasing severity categories of DSWMH (91.7, 91.2, and 90.4; p for trend = 0.011) and PVH (91.5, 90.4, and 89.7; p for trend = 0.006). Other SCDs did not show significant associations. In stratified analyses based on the presence or absence of each SCD, both DSWMH and PVH demonstrated significant inverse trends with CASI scores in the absence of lacunar infarcts and microbleeds and in the presence of ICAS. Additionally, among participants with PVH (+), ≥moderate ICAS was significantly associated with lower CASI scores. Conclusion: PVH and DSWMH showed significant dose-response relationships with cognitive function among community-based Japanese men. These findings suggest that white matter lesions may be an important indicator of early cognitive impairment, and severe ICAS may also play a role in those with PVH. en-copyright= kn-copyright= en-aut-name=ItoTakahiro en-aut-sei=Ito en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 ORCID= en-aut-name=ShitaraSatoshi en-aut-sei=Shitara en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyagawaNaoko en-aut-sei=Miyagawa en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SegawaHiroyoshi en-aut-sei=Segawa en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= en-aut-name=TooyamaIkuo en-aut-sei=Tooyama en-aut-mei=Ikuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WatanabeYoshiyuki en-aut-sei=Watanabe en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YoshidaKazumichi en-aut-sei=Yoshida en-aut-mei=Kazumichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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=16 ORCID= en-aut-name=The SESSA Research Group en-aut-sei=The SESSA Research Group en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Radiology, Shiga University of Medical Science kn-affil= affil-num=2 en-affil=Department of Radiology, Shiga University of Medical Science kn-affil= affil-num=3 en-affil=Department of Hygiene and Public Health, Teikyo University School of Medicine kn-affil= affil-num=4 en-affil=Molecular Neuroscience Research Center, Shiga University of Medical Science kn-affil= affil-num=5 en-affil=Department of Neurosurgery, Shiga University of Medical Science kn-affil= affil-num=6 en-affil=Department of Preventive Medicine and Public Health, Keio University School of Medicine kn-affil= affil-num=7 en-affil=Department of Radiology, Shiga University of Medical Science kn-affil= affil-num=8 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Radiology, Shiga University of Medical Science kn-affil= affil-num=10 en-affil=Department of Radiology, Shiga University of Medical Science kn-affil= affil-num=11 en-affil=Department of Radiology, Shiga University of Medical Science kn-affil= affil-num=12 en-affil=Molecular Neuroscience Research Center, Shiga University of Medical Science kn-affil= affil-num=13 en-affil=Department of Radiology, Shiga University of Medical Science kn-affil= affil-num=14 en-affil=Department of Neurosurgery, Shiga University of Medical Science kn-affil= affil-num=15 en-affil=Department of Neurosurgery, Shiga University of Medical Science kn-affil= affil-num=16 en-affil=Department of Radiology, Shiga University of Medical Science kn-affil= affil-num=17 en-affil= kn-affil= en-keyword=Cognitive impairment kn-keyword=Cognitive impairment en-keyword=Cerebrovascular disease kn-keyword=Cerebrovascular disease en-keyword=Brain magnetic resonance imaging kn-keyword=Brain magnetic resonance imaging en-keyword=White matter lesion kn-keyword=White matter lesion en-keyword=Community-based population study kn-keyword=Community-based population study END start-ver=1.4 cd-journal=joma no-vol=287 cd-vols= no-issue= article-no= start-page=117674 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A plant-insertable multi-enzyme biosensor for the real-time monitoring of stomatal sucrose uptake en-subtitle= kn-subtitle= en-abstract= kn-abstract=Monitoring sucrose transport in plants is essential for understanding plant physiology and improving agricultural practices, yet effective sensors for continuous and real-time in-vivo monitoring are lacking. In this study, we developed a plant-insertable sucrose sensor capable of real-time sucrose concentration monitoring and demonstrated its application as a useful tool for plant research by monitoring the sugar-translocating path from leaves to the lower portion of plants through the stem in living plants. The biosensor consists of a bilirubin oxidase-based biocathode and a needle-type bioanode integrating glucose oxidase, invertase, and mutarotase, with the two electrodes separated by an agarose gel for ionic connection. The sensor exhibits a sensitivity of 6.22 μA mM−1 cm−2, a limit of detection of 100 μM, a detection range up to 60 mM, and a response time of 90 s at 100 μM sucrose. Additionally, the sensor retained 86 % of its initial signal after 72 h of continuous measurement. Day-night monitoring from the biosensor inserted in strawberry guava (Psidium cattleianum) showed higher sucrose transport activity at night, following well the redistribution of photosynthetically produced sugars. In addition, by monitoring the forced translocation of sucrose dissolved in the stable isotopically labeled water, we demonstrated that a young seedling of Japanese cedar known as Sugi (Cryptomeria japonica) can absorb and transport both water and sucrose through light-dependently opened stomata, which is the recently revealed path for liquid uptake by higher plants. These findings highlight the potential of our sensor for studying dynamic plant processes and its applicability in real-time monitoring of sugar transport under diverse environmental conditions. en-copyright= kn-copyright= en-aut-name=WuShiqi en-aut-sei=Wu en-aut-mei=Shiqi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakagawaWakutaka en-aut-sei=Nakagawa en-aut-mei=Wakutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriYuki en-aut-sei=Mori en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AzhariSaman en-aut-sei=Azhari en-aut-mei=Saman kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MéhesGábor en-aut-sei=Méhes en-aut-mei=Gábor kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawanoTomonori en-aut-sei=Kawano en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyakeTakeo en-aut-sei=Miyake en-aut-mei=Takeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Information, Production and Systems, Waseda University kn-affil= affil-num=2 en-affil=Graduate School of Information, Production and Systems, Waseda University kn-affil= affil-num=3 en-affil=Faculty and Graduate School of Environmental Engineering, The University of Kitakyushu kn-affil= affil-num=4 en-affil=Graduate School of Information, Production and Systems, Waseda University kn-affil= affil-num=5 en-affil=Graduate School of Information, Production and Systems, Waseda University kn-affil= affil-num=6 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=7 en-affil=Faculty and Graduate School of Environmental Engineering, The University of Kitakyushu kn-affil= affil-num=8 en-affil=Graduate School of Information, Production and Systems, Waseda University kn-affil= en-keyword=Flexible wearable sensor kn-keyword=Flexible wearable sensor en-keyword=Plant monitoring kn-keyword=Plant monitoring en-keyword=Carbon fiber kn-keyword=Carbon fiber en-keyword=Multi-enzyme system kn-keyword=Multi-enzyme system END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=10 article-no= start-page=2373 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241017 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development and Characterization of a Three-Dimensional Organotypic In Vitro Oral Cancer Model with Four Co-Cultured Cell Types, Including Patient-Derived Cancer-Associated Fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Cancer organoids have emerged as a valuable tool of three-dimensional (3D) cell cultures to investigate tumor heterogeneity and predict tumor behavior and treatment response. We developed a 3D organotypic culture model of oral squamous cell carcinoma (OSCC) to recapitulate the tumor–stromal interface by co-culturing four cell types, including patient-derived cancer-associated fibroblasts (PD-CAFs). Methods: A stainless-steel ring was used twice to create the horizontal positioning of the cancer stroma (adjoining normal oral mucosa connective tissue) and the OSCC layer (surrounding normal oral mucosa epithelial layer). Combined with a structured bi-layered model of the epithelial component and the underlying stroma, this protocol enabled us to construct four distinct portions mimicking the oral cancer tissue arising in the oral mucosa. Results: In this model, α-smooth muscle actin-positive PD-CAFs were localized in close proximity to the OSCC layer, suggesting a crosstalk between them. Furthermore, a linear laminin-γ2 expression was lacking at the interface between the OSCC layer and the underlying stromal layer, indicating the loss of the basement membrane-like structure. Conclusions: Since the specific 3D architecture and polarity mimicking oral cancer in vivo provides a more accurate milieu of the tumor microenvironment (TME), it could be crucial in elucidating oral cancer TME. en-copyright= kn-copyright= en-aut-name=AizawaYuka en-aut-sei=Aizawa en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagaKenta en-aut-sei=Haga en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshibaNagako en-aut-sei=Yoshiba en-aut-mei=Nagako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YortchanWitsanu en-aut-sei=Yortchan en-aut-mei=Witsanu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakadaSho en-aut-sei=Takada en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaRintaro en-aut-sei=Tanaka en-aut-mei=Rintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NaitoEriko en-aut-sei=Naito en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AbéTatsuya en-aut-sei=Abé en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaruyamaSatoshi en-aut-sei=Maruyama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamazakiManabu en-aut-sei=Yamazaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TanumaJun-ichi en-aut-sei=Tanuma en-aut-mei=Jun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IgawaKazuyo en-aut-sei=Igawa en-aut-mei=Kazuyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TomiharaKei en-aut-sei=Tomihara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TogoShinsaku en-aut-sei=Togo en-aut-mei=Shinsaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IzumiKenji en-aut-sei=Izumi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=2 en-affil=Division of Reconstructive Surgery for Oral and Maxillofacial Region, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=3 en-affil=Department of Oral Health and Welfare, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=4 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=5 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=6 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=7 en-affil=Division of Oral and Maxillofacial Surgery, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=8 en-affil=Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=9 en-affil=Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=10 en-affil=Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=11 en-affil=Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=12 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=13 en-affil=Division of Oral and Maxillofacial Surgery, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, Graduate School of Medicine, Juntendo University kn-affil= affil-num=15 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= en-keyword=oral cancer kn-keyword=oral cancer en-keyword=cancer-associated fibroblasts kn-keyword=cancer-associated fibroblasts en-keyword=oral mucosa kn-keyword=oral mucosa en-keyword=patient-derived kn-keyword=patient-derived en-keyword=organotypic culture kn-keyword=organotypic culture en-keyword=3D in vitro model kn-keyword=3D in vitro model en-keyword=polarity kn-keyword=polarity END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=roaf042 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Recommendations for the treatment of juvenile idiopathic arthritis with oligoarthritis or polyarthritis from the 2024 update of the Japan College of Rheumatology Clinical Practice Guidelines for the management of rheumatoid arthritis including juvenile idiopathic arthritis with oligoarthritis or polyarthritis – secondary publication en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: To conduct systematic reviews (SRs) and develop clinical practice guidelines (CPGs) for managing juvenile idiopathic arthritis (JIA) with oligoarthritis or polyarthritis.
Methods: The Grading of Recommendations, Assessment, Development, and Evaluation methodology was employed to carry out SRs and formulate the CPGs. An expert panel, including patients, paediatric and nonpaediatric rheumatologists, guideline specialists, and patient representatives, used the Delphi method to discuss and agree on the recommendations.
Results: Six clinical questions (CQs) on the efficacy and safety of medical treatments were evaluated. These included CQ1 on methotrexate (MTX), CQ2 on non-MTX conventional synthetic disease-modifying antirheumatic drugs, CQ3 on glucocorticoids, CQ4 on tumour necrosis factor inhibitors, CQ5 on interleukin-6 inhibitors, and CQ6 on Janus kinase inhibitors. Two randomized controlled trials were identified for CQ1, three for CQ2, two for CQ3, eight for CQ4, two for CQ5, and two for CQ6. Based on these evaluations, three strong and three conditional recommendations were established. The CPGs have been endorsed by the Japan College of Rheumatology and the Pediatric Rheumatology Association of Japan.
Conclusions: The SRs provided the necessary evidence to develop the CPGs, which are intended to guide not only paediatric but also nonpaediatric rheumatologists, caregivers, patients, and their families in treatment decision-making. en-copyright= kn-copyright= en-aut-name=MiyamaeTakako en-aut-sei=Miyamae en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkamotoNami en-aut-sei=Okamoto en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InoueYuzaburo en-aut-sei=Inoue en-aut-mei=Yuzaburo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KubotaTomohiro en-aut-sei=Kubota en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EbatoTakasuke en-aut-sei=Ebato en-aut-mei=Takasuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IrabuHitoshi en-aut-sei=Irabu en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KamedaHideto en-aut-sei=Kameda en-aut-mei=Hideto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanekoYuko en-aut-sei=Kaneko en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KuboHiroshi en-aut-sei=Kubo en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MitsunagaKanako en-aut-sei=Mitsunaga en-aut-mei=Kanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MoriMasaaki en-aut-sei=Mori en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakajimaAyako en-aut-sei=Nakajima en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NishimuraKenichi en-aut-sei=Nishimura en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OhkuboNaoaki en-aut-sei=Ohkubo en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SatoTomomi en-aut-sei=Sato en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SugitaYuko en-aut-sei=Sugita en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakanashiSatoshi en-aut-sei=Takanashi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TanakaTakayuki en-aut-sei=Tanaka en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=UmebayashiHiroaki en-aut-sei=Umebayashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YamanishiShingo en-aut-sei=Yamanishi en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=FusamaMie en-aut-sei=Fusama en-aut-mei=Mie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=HirataShintaro en-aut-sei=Hirata en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KishimotoMitsumasa en-aut-sei=Kishimoto en-aut-mei=Mitsumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KohnoMasataka en-aut-sei=Kohno en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KojimaMasayo en-aut-sei=Kojima en-aut-mei=Masayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KojimaToshihisa en-aut-sei=Kojima en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MorinobuAkio en-aut-sei=Morinobu en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=SugiharaTakahiko en-aut-sei=Sugihara en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=TanakaEiichi en-aut-sei=Tanaka en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=YajimaNobuyuki en-aut-sei=Yajima en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=YanaiRyo en-aut-sei=Yanai en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=KawahitoYutaka en-aut-sei=Kawahito en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=HarigaiMasayoshi en-aut-sei=Harigai en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= affil-num=1 en-affil=Department of Pediatric Rheumatology, Institute of Rheumatology, Tokyo Women’s Medical University Hospital kn-affil= affil-num=2 en-affil=Department of Pediatrics, Osaka Rosai Hospital, Japan Organization of Occupational Health and Safety kn-affil= affil-num=3 en-affil=Department of General Medical Science, Graduate School of Medicine, Chiba University kn-affil= affil-num=4 en-affil=Department of Pediatrics, Kagoshima Prefectural Satsunan Hospital kn-affil= affil-num=5 en-affil=Department of Pediatrics, Kitasato University kn-affil= affil-num=6 en-affil=Department of Pediatrics and Development Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University kn-affil= affil-num=7 en-affil=Division of Rheumatology, Department of Internal Medicine, Toho University kn-affil= affil-num=8 en-affil=Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=10 en-affil=Department of Allergy and Rheumatology, Chiba Children's Hospital kn-affil= affil-num=11 en-affil=Department of Lifetime Clinical Immunology, Tokyo Medical and Dental University kn-affil= affil-num=12 en-affil=Center for Rheumatic Diseases, Mie University Hospital kn-affil= affil-num=13 en-affil=Department of Pediatrics, Yokohama City University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Iizuka Hospital kn-affil= affil-num=15 en-affil=Clinical Education Center For Physicians, Shiga University of Medical Science kn-affil= affil-num=16 en-affil=Department of Pediatrics, School of Medicine, Osaka Medical and Pharmaceutical University kn-affil= affil-num=17 en-affil=Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=18 en-affil=Department of Pediatrics, Japanese Red Cross Otsu Hospital kn-affil= affil-num=19 en-affil=Department of Rheumatology and Infectious Diseases, Miyagi Children’s Hospital kn-affil= affil-num=20 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=21 en-affil=Department of Pediatrics, Nippon Medical School kn-affil= affil-num=22 en-affil=Health Sciences Department of Nursing, Kansai University of International Studies kn-affil= affil-num=23 en-affil=Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital kn-affil= affil-num=24 en-affil=Department of Nephrology and Rheumatology, Kyorin University School of Medicine kn-affil= affil-num=25 en-affil=Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=26 en-affil=Graduate School of Medical Sciences, Nagoya City University kn-affil= affil-num=27 en-affil=Department of Orthopedic Surgery, National Hospital Organization Nagoya Medical Center kn-affil= affil-num=28 en-affil=Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=29 en-affil=Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine kn-affil= affil-num=30 en-affil=Division of Rheumatology, Department of Internal Medicine, School of Medicine, Tokyo Women's Medical University kn-affil= affil-num=31 en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine kn-affil= affil-num=32 en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine kn-affil= affil-num=33 en-affil=Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=34 en-affil=Division of Rheumatology, Department of Internal Medicine, School of Medicine, Tokyo Women's Medical University kn-affil= en-keyword=Clinical practice guidelines kn-keyword=Clinical practice guidelines en-keyword=baricitinib kn-keyword=baricitinib en-keyword=GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) kn-keyword=GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) en-keyword=juvenile idiopathic arthritis kn-keyword=juvenile idiopathic arthritis en-keyword=systematic review kn-keyword=systematic review END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue= article-no= start-page=244 end-page=256 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Postnatal expression of Cat-315-positive perineuronal nets in the SAMP10 mouse primary somatosensory cortex en-subtitle= kn-subtitle= en-abstract= kn-abstract=Perineuronal nets (PNNs) form at the end of the critical period of plasticity in the mouse primary somatosensory cortex. PNNs are said to have functions that control neuroplasticity and provide neuroprotection. However, it is not clear which molecules in PNNs have these functions. We have previously reported that Cat-315-positive molecules were not expressed in the PNNs of the senescence-accelerated model (SAM)P10 strain model mice at 12 months of age. To confirm whether the loss of Cat-315-positive molecules occurred early in life in SAMP10 mice, we examined Cat-315-positive PNNs in the primary somatosensory cortex during postnatal development. This research helps to elucidate the function of PNNs and the mechanism of cognitive decline associated with ageing. To confirm whether Cat-315-positive PNNs changed in an age-dependent manner in SAMP10 mice, we examined the primary somatosensory cortex at 21, 28, and 56 days after birth. We compared these results with those of senescence-accelerated mouse-resistant (SAMR) mice. In SAMP10 mice, Cat-315-positive PNNs were expressed in the primary somatosensory cortex early after birth, but their expression was significantly lower than that in SAMR1 mice. Many other molecules that calibrated the PNN were unchanged between SAMP10 and SAMR1 mice. This study revealed that the expression of the Cat-315 epitope was decreased in the primary somatosensory cortex of SAMP10 mice during postnatal development. SAMP10 mice have had histological abnormalities in their brains since early life. Furthermore, using SAMP10 will be useful in elucidating the mechanism of age-related abnormalities in brain function as well as in elucidating the function and structure of PNNs. en-copyright= kn-copyright= en-aut-name=UenoHiroshi en-aut-sei=Ueno en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiYu en-aut-sei=Takahashi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriSachiko en-aut-sei=Mori en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitanoEriko en-aut-sei=Kitano en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiShinji en-aut-sei=Murakami en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WaniKenta en-aut-sei=Wani en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoYosuke en-aut-sei=Matsumoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoMotoi en-aut-sei=Okamoto en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshiharaTakeshi en-aut-sei=Ishihara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Medical Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=2 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= en-keyword=Ageing kn-keyword=Ageing en-keyword=Brain function kn-keyword=Brain function en-keyword=Neuroplasticity kn-keyword=Neuroplasticity en-keyword=Neuroprotection kn-keyword=Neuroprotection en-keyword=Cognitive decline kn-keyword=Cognitive decline END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Age-related behavioural abnormalities in C57BL/6.KOR–Apoe shl mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Spontaneously hyperlipidaemic (Apoeshl) mice were discovered in 1999 as mice lacking apolipoprotein E (ApoE) owing to a mutation in the Apoe gene. However, age-related behavioural changes in commercially available Apoeshl mice have not yet been clarified. The behavioural abnormalities of ApoE-deficient mice, which are genetically modified mice artificially deficient in ApoE, have been investigated in detail, and it has been reported that they can serve as a model of Alzheimer’s disease (AD). To understand whether Apoeshl mice can also serve as a murine model of AD, it is necessary to investigate age-related behavioural abnormalities in Apoeshl mice. In this study, we conducted a series of behavioural experiments on 7- and 11-month-old Apoeshl mice to investigate the behavioural abnormalities associated with ageing in Apoeshl mice. In this study, 7-month-old Apoeshl mice showed decreased body weight and grip strength compared to age-matched wild-type mice. In the open field test, 7-month-old Apoeshl mice showed increased anxiety-like behaviour compared to wild-type mice, whereas 11-month-old Apoeshl mice showed decreased anxiety-like behaviour. Moreover, Apoeshl mice aged 7 and 11 months had increased serum cholesterol levels. These results indicate that the behaviour of Apoeshl mice changes with age. However, 11-month-old Apoeshl mice did not show a decline in cognitive function or memory ability similar to murine models of AD. Our findings indicate that Apoeshl mice can be used to investigate the function of ApoE in the central nervous system. en-copyright= kn-copyright= en-aut-name=UenoHiroshi en-aut-sei=Ueno en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiYu en-aut-sei=Takahashi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriSachiko en-aut-sei=Mori en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitanoEriko en-aut-sei=Kitano en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiShinji en-aut-sei=Murakami en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WaniKenta en-aut-sei=Wani en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyazakiTetsuji en-aut-sei=Miyazaki en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsumotoYosuke en-aut-sei=Matsumoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkamotoMotoi en-aut-sei=Okamoto en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiharaTakeshi en-aut-sei=Ishihara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Medical Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=2 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=8 en-affil=Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= en-keyword=age kn-keyword=age en-keyword=apolipoprotein kn-keyword=apolipoprotein en-keyword=behavioural test kn-keyword=behavioural test en-keyword=central nervous system kn-keyword=central nervous system en-keyword=mouse kn-keyword=mouse END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250222 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rearing in an envy-like environment increases anxiety-like behaviour in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Interest in the societal and psychological harm caused by widespread envy and social comparison is increasing. Envy is associated with anxiety and depression, though the mechanism by which envy affects neuropsychiatric disorders, such as depression, remains unclear. Clarifying the neurobiological basis of envy’s effects on behaviour and emotion regulation in experimental mice is essential for developing disease-prevention and treatment strategies. As mice recognize other mice in neighbouring cages, this study investigated whether they recognize neighbouring cages housed in environmentally enriched cages and suffer psychological stress due to envy. After being raised in an envy-like environment for 3 weeks, we revealed changes in the behaviour of the mice through a series of behavioural experiments. Mice raised in an envious environment showed increased body weight and anxiety-like behaviour but decreased social behaviour and serum corticosterone levels compared to control mice. Thus, mice recognize their neighbouring cages and experience psychological stress due to envy. This study revealed a part of the scientific basis for why envy increased anxiety. Using this novel experimental breeding environment, it may be possible to create an experimental animal model of anxiety disorders. en-copyright= kn-copyright= en-aut-name=UenoHiroshi en-aut-sei=Ueno en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitanoEriko en-aut-sei=Kitano en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiYu en-aut-sei=Takahashi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriSachiko en-aut-sei=Mori en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiShinji en-aut-sei=Murakami en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WaniKenta en-aut-sei=Wani en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoYosuke en-aut-sei=Matsumoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoMotoi en-aut-sei=Okamoto en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshiharaTakeshi en-aut-sei=Ishihara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Medical Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=2 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= en-keyword=behaviour kn-keyword=behaviour en-keyword=anxiety kn-keyword=anxiety en-keyword=mouse kn-keyword=mouse en-keyword=envy kn-keyword=envy en-keyword=rodent kn-keyword=rodent END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=2 article-no= start-page=156 end-page=167 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Metaverse Support Groups for LGBTQ+ Youth: An Observational Study on Safety, Self-Expression, and Early Intervention en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study explored whether metaverse-based support groups could address social isolation and suicide risks among LGBTQ+ youths by providing enhanced anonymity, avatar-based self-expression, and improved accessibility. Over one year, 53 individuals aged 14–23 participated in regular online sessions facilitated via the "cluster" metaverse platform by a non-profit LGBTQ+ organization. Each 90-minute session included voice and text-based interactions within a specially designed single-floor virtual space featuring conversation areas and a designated "safe area" for emotional regulation. Post-session questionnaires (5-point Likert scales) captured demographics, avatar preferences, self-confidence, and perceived safety, self-expression, and accessibility; responses were analyzed with Pearson's chi-squared test and Mann–Whitney U tests (α=0.05). Results indicated that 79.2% of participants selected avatars aligned with their gender identity, reporting high satisfaction (mean = 4.10/5) and minimal discomfort (mean = 1.79/5). Social confidence was significantly higher in the metaverse compared with real-world settings (p<0.001), particularly among those with lower real-world confidence, who exhibited an average gain of 2.08 points. Approximately half of all first-time participants were aged 16 years or younger, which suggested the platform’s value for early intervention. Additionally, the metaverse environment was rated significantly higher in safety/privacy (3.94/5), self-expression (4.02/5), and accessibility (4.21/5) compared with the real-world baseline, and 73.6% reported they felt more accepted virtually. However, some participants who had high confidence offline experienced mild adaptation challenges (mean decrease of 0.58 points), which highlighted that metaverse-based support may be more effective as a complement to in-person services rather than a replacement. Overall, these findings demonstrate that metaverse-based support groups can reduce psychological barriers for LGBTQ+ youth by facilitating safe and affirming virtual environments. The metaverse may help alleviate emotional distress and prevent further severe outcomes, such as suicidal ideation by providing early intervention, especially for adolescents unable to access conventional in-person services. Further research should examine its integration with existing clinical, community, and educational resources to ensure comprehensive, long-term support. en-copyright= kn-copyright= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoYosuke en-aut-sei=Matsumoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaiHiroki en-aut-sei=Kawai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkahisaYuko en-aut-sei=Okahisa en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=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 Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceu-tical Sciences, Okayama University kn-affil= en-keyword=LGBTQ+ Youth kn-keyword=LGBTQ+ Youth en-keyword=Social Isolation kn-keyword=Social Isolation en-keyword=Suicide Prevention kn-keyword=Suicide Prevention en-keyword=Avatar-Based Interventions kn-keyword=Avatar-Based Interventions END start-ver=1.4 cd-journal=joma no-vol=390 cd-vols= no-issue= article-no= start-page=116594 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Extension-type flexible pneumatic actuator with a large extension force using a cross-link mechanism based on pantographs en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this study, we propose an extension-type flexible pneumatic actuator (EFPA) with a high extension force and no buckling. In a previous study, soft actuators that extended in the axial direction by applying a supply pressure were unable to generate the extension’s pushing force because the actuators buckled owing to their high flexibility. To generate a pushing force, the circumferential stiffness of an extension-type flexible soft actuator must be reinforced. Therefore, a cross-linked EFPA (CL-EFPA) was developed, inspired by a pantograph that restrains the EFPA three-dimensionally using the proposed link mechanism. The proposed CL-EFPA consists of three EFPAs and a cross-linking mechanism for integrating each EFPA circumference. The pushing force of the CL-EFPA is approximately 3.0 times compared with that generated by the previous EFPA with plates to restrain its plane. To perform various bending motions, attitude control was performed using an analytical model and a system that included valves, sensors, and controllers. en-copyright= kn-copyright= en-aut-name=ShimookaSo en-aut-sei=Shimooka en-aut-mei=So kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TadachiKazuma en-aut-sei=Tadachi en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Mechanical and Systems Engineering Program, School of Engineering, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Soft robot kn-keyword=Soft robot en-keyword=Extension soft actuator kn-keyword=Extension soft actuator en-keyword=Link mechanism kn-keyword=Link mechanism en-keyword=Pantograph kn-keyword=Pantograph en-keyword=Attitude control kn-keyword=Attitude control END start-ver=1.4 cd-journal=joma no-vol=37 cd-vols= no-issue=1 article-no= start-page=43 end-page=53 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fan-Shaped Pneumatic Soft Actuator that Can Operate Bending Motion for Ankle-Joint Rehabilitation Device en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nowadays, owing to declining birthrates and an aging population, patients and the elderly requiring rehabilitation are not getting enough physical activity. In addressing this issue, devices for rehabilitating them have been researched and developed. However, rehabilitation devices are almost exclusively used for patients who can get up, rather than those who are bedridden. In this study, we aim to develop a rehabilitation device that can provide passive exercise for bedridden patients. The ankle joint was selected as the target joint because the patients who have undergone surgery for cerebrovascular disease remain bedridden, and early recovery in the acute stage is highly desirable. We proposed and tested a fan-shaped pneumatic soft actuator (FPSA) that can expand and bend stably at angles when supply pressure is applied as an actuator for a rehabilitation device to encourage patient exercise. However, the previous FPSA’s movement deviates from the arch of the foot owing to increased supply pressure. In the ideal case, FPSA should push the arch of the foot in an arc motion. This study proposes and tests the FPSA that can operate a bending motion to provide passive exercise to the ankle joint using tensile springs and a winding mechanism powered by a servo motor. The proposed FPSA has a significant advantage of exhibiting no hysteresis in its pressure-displacement characteristics. The configuration and static analytical model of the improved FPSA are described. en-copyright= kn-copyright= en-aut-name=ShimookaSo en-aut-sei=Shimooka en-aut-mei=So kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokoyaHirosato en-aut-sei=Yokoya en-aut-mei=Hirosato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamadaMasanori en-aut-sei=Hamada en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShiomiShun en-aut-sei=Shiomi en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UeharaTakenori en-aut-sei=Uehara en-aut-mei=Takenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HirayamaTakahiro en-aut-sei=Hirayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KamegawaTetsushi en-aut-sei=Kamegawa en-aut-mei=Tetsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, NHO Okayama Medical Center kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=fan-shaped pneumatic soft actuator kn-keyword=fan-shaped pneumatic soft actuator en-keyword=ankle-joint rehabilitation device kn-keyword=ankle-joint rehabilitation device en-keyword=hysteresis kn-keyword=hysteresis en-keyword=range of motion kn-keyword=range of motion END start-ver=1.4 cd-journal=joma no-vol=329 cd-vols= no-issue=1 article-no= start-page=L183 end-page=L196 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250701 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Activated factor X inhibition ameliorates NF-κB-IL-6-mediated perivascular inflammation and pulmonary hypertension en-subtitle= kn-subtitle= en-abstract= kn-abstract=Activated factor X (FXa) induces inflammatory response and cell proliferation in various cell types via activation of proteinase-activated receptor-1 (PAR1) and/or PAR2. We thus aimed to investigate the impact of FXa on the development of pulmonary arterial hypertension (PAH) and the mechanisms involved. The effects of edoxaban, a selective FXa inhibitor, on hemodynamic, right ventricular (RV) hypertrophy, and vascular remodeling were evaluated in a monocrotaline (MCT)-exposed pulmonary hypertension (PH) rat model. At 21 days after a single subcutaneous injection of MCT of 60 mg/kg, right ventricular systolic pressure (RVSP) and total pulmonary vascular resistance index (TPRI) were elevated concomitant with the increased plasma FXa and lung interleukin-6 (IL-6) mRNA. Daily administration of edoxaban (10 mg/kg/day, by gavage) starting from the day of MCT injection for 21 days ameliorated RVSP, TPRI, RV hypertrophy, pulmonary vascular remodeling, and macrophage accumulation. Edoxaban reduced nuclear factor-kappa B (NF-κB) activity and IL-6 mRNA level in the lungs of MCT-exposed rats. mRNA levels of FXa, PAR1, and PAR2 in cultured pulmonary arterial smooth muscle cells (PASMCs) isolated from patients with PAH were higher than those seen in normal PASMCs. FXa stimulation increased cell proliferation and mRNA level of IL-6 in normal PASMCs, both of which were blunted by edoxaban and PAR1 antagonist. Moreover, FXa stimulation activated extracellularly regulated kinases 1/2 in a PAR1-dependent manner. Inhibition of FXa ameliorates NF-κB-IL-6-mediated perivascular inflammation, pulmonary vascular remodeling, and the development of PH in MCT-exposed rats, suggesting that FXa may be a potential target for the treatment of PAH.
NEW & NOTEWORTHY This study demonstrated that chronic treatment with activated factor X (FXa) inhibitor ameliorated NF-κB-IL-6-mediated perivascular inflammation in a rat model with pulmonary arterial hypertension, which is associated with elevated FXa activity. FXa may act on pulmonary arterial smooth muscle cells, inducing cell proliferation and inflammatory response via upregulated PAR1, thereby contributing to pulmonary vascular remodeling. Understanding the patient-specific pathophysiology is a prerequisite for applying FXa-targeted therapy to the treatment of pulmonary arterial hypertension. en-copyright= kn-copyright= en-aut-name=ImakiireSatomi en-aut-sei=Imakiire en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuroKeiji en-aut-sei=Kimuro en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshidaKeimei en-aut-sei=Yoshida en-aut-mei=Keimei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MasakiKohei en-aut-sei=Masaki en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IzumiRyo en-aut-sei=Izumi en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ImabayashiMisaki en-aut-sei=Imabayashi en-aut-mei=Misaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanabeTakanori en-aut-sei=Watanabe en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IshikawaTomohito en-aut-sei=Ishikawa en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HosokawaKazuya en-aut-sei=Hosokawa en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsushimaShouji en-aut-sei=Matsushima en-aut-mei=Shouji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HashimotoToru en-aut-sei=Hashimoto en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShinoharaKeisuke en-aut-sei=Shinohara en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KatsukiShunsuke en-aut-sei=Katsuki en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MatobaTetsuya en-aut-sei=Matoba en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HiranoKatsuya en-aut-sei=Hirano en-aut-mei=Katsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TsutsuiHiroyuki en-aut-sei=Tsutsui en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=AbeKohtaro en-aut-sei=Abe en-aut-mei=Kohtaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=11 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=13 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=14 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=15 en-affil=Department of Cardiovascular Medicine, Okayama University kn-affil= affil-num=16 en-affil=Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University kn-affil= affil-num=17 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=18 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= en-keyword=factor Xa kn-keyword=factor Xa en-keyword=IL-6 kn-keyword=IL-6 en-keyword=proteinase-activated receptor kn-keyword=proteinase-activated receptor en-keyword=pulmonary arterial hypertension kn-keyword=pulmonary arterial hypertension en-keyword=pulmonary hypertension kn-keyword=pulmonary hypertension END start-ver=1.4 cd-journal=joma no-vol=487 cd-vols= no-issue= article-no= start-page=137307 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Co-precipitating calcium phosphate as oral detoxification of cadmium en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bone-eating (also known as osteophagia), found in wild animals, is primarily recognized as a means to supplement phosphorus and calcium intake. Herein, we describe a novel function of bone-eating in detoxifying heavy metal ions through the dissolution and co-precipitation of bone minerals as they travel through the gastrointestinal (GI) tract. In this study, cadmium (Cd), a heavy metal ion, served as a toxic model. We demonstrated that hydroxyapatite (HAp), the major calcium phosphate (CaP) in bone, dissolves in the stomach and acts as a co-precipitant in the intestine for Cd detoxification. We compared HAp to a common antidote, activated charcoal (AC), which did not precipitate within the GI tract. In vitro experiments showed that HAp dissolves under acidic conditions and, upon return to a neutral environment, efficiently re-sequesters Cd. Similarly, oral administration of HAp effectively prevented Cd absorption and accumulation, resulting in enhanced Cd excretion in the feces when compared to AC. A co-precipitating CaP in the GI tract could serve as an excellent detoxification system, as it helps prevent the accumulation of toxic substances and aids in developing appropriate strategies to reduce tissue toxicity. Moreover, understanding this detoxification system would be a valuable indicator for designing efficient detoxification materials. en-copyright= kn-copyright= en-aut-name=BikharudinAhmad en-aut-sei=Bikharudin en-aut-mei=Ahmad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkadaMasahiro en-aut-sei=Okada en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SungPing-chin en-aut-sei=Sung en-aut-mei=Ping-chin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoTakuya en-aut-sei=Matsumoto en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Cadmium detoxification kn-keyword=Cadmium detoxification en-keyword=Coprecipitation kn-keyword=Coprecipitation en-keyword=Calcium phosphate kn-keyword=Calcium phosphate en-keyword=Gastrointestinal tract kn-keyword=Gastrointestinal tract END start-ver=1.4 cd-journal=joma no-vol=56 cd-vols= no-issue=1 article-no= start-page=64 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250527 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluating a discretized data acquisition method for couch modeling to streamline the commissioning process of radiological instruments en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The commissioning of radiotherapy treatment planning system (RTPS) involves many time-consuming tests to maintain consistency between actual and planned dose. As the number of new technologies and peripheral devices increases year by year, there is a need for time-efficient and accurate commissioning of radiation therapy equipment. Couch modeling is one type of commissioning, and there are no recommended values for CT due to differences in equipment calibration between facilities. This study evaluated the optimal electron density (ED) for the couch using discretized gantry angles.
Results All discrete-angle groups showed a high correlation between the surface ED and dose difference between the actual and planned doses (|r|> 0.9). AcurosXB did not demonstrate a significant correlation between dose differences and each energy. For a small number of discretized gantry groups, the optimal couch modeling results revealed several combinations of surface and interior ED with the same score. Upon adding all couch thickness scores, all energy scores, and both algorithm scores, the optimal surface and interior EDs with the highest score across all couch thicknesses were 0.4 and 0.07, respectively.
Conclusions The optimal couch surface ED dose difference trend was identified, and the effectiveness indicated using the dose difference score from discrete-angle couch modeling. Using this method, couch modeling can be evaluated in a highly precise and quick manner, which helps in the commissioning of complicated linear accelerator and radiological treatment plans. en-copyright= kn-copyright= en-aut-name=TomimotoSyouta en-aut-sei=Tomimoto en-aut-mei=Syouta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaekiYusuke en-aut-sei=Saeki en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotodaOkihiro en-aut-sei=Motoda en-aut-mei=Okihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaMasato en-aut-sei=Tanaka en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsumotoSyouki en-aut-sei=Tsumoto en-aut-mei=Syouki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishikawaHana en-aut-sei=Nishikawa en-aut-mei=Hana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyashimaYuki en-aut-sei=Miyashima en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiguchiMakiko en-aut-sei=Higuchi en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TaniTadashi en-aut-sei=Tani en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=TanabeYoshinori en-aut-sei=Tanabe en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Radiological Technology, Faculty of Medicine, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Kawasaki Medical School Hospital kn-affil= affil-num=3 en-affil=Department of Radiological Technology, Kawasaki Medical School Hospital kn-affil= affil-num=4 en-affil=Department of Radiological Technology, Kawasaki Medical School Hospital kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Faculty of Medicine, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Radiological Technology, Faculty of Medicine, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Radiological Technology, Kawasaki Medical School Hospital kn-affil= affil-num=8 en-affil=Department of Radiological Technology, Kawasaki Medical School Hospital kn-affil= affil-num=9 en-affil=Department of Radiological Technology, Kawasaki Medical School Hospital kn-affil= affil-num=10 en-affil=Department of Radiology, Kawasaki Medical School kn-affil= affil-num=11 en-affil=Department of Radiological Technology, Faculty of Medicine, Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=Couch modeling kn-keyword=Couch modeling en-keyword=Commissioning kn-keyword=Commissioning en-keyword=Attenuation of couch kn-keyword=Attenuation of couch en-keyword=Linear accelerator kn-keyword=Linear accelerator en-keyword=Radiotherapy planning system kn-keyword=Radiotherapy planning system END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=2 article-no= start-page=373 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Asia-Pacific Body Mass Index Classification and New-Onset Chronic Kidney Disease in Non-Diabetic Japanese Adults: A Community-Based Longitudinal Study from 1998 to 2023 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Obesity is a risk factor for chronic kidney disease (CKD) in Asians. The Asia-Pacific body mass index (BMI) classification sets lower obesity cutoffs than the conventional BMI classification for all races, generally reflecting the lower BMIs in Asians. This longitudinal study evaluated the association between BMI, as classified by the Asia-Pacific BMI system, and CKD development in non-diabetic Asian adults. Methods: A population-based longitudinal study (1998–2023) was conducted in non-diabetic Japanese adults (hemoglobin A1c < 6.5%) in Zentsuji City (Kagawa Prefecture, Japan). The generalized gamma model was used to assess the relationship between time-varying BMI categories and CKD development, stratified by sex. CKD was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2. BMI was calculated as weight (kg) divided by the square of height (m2) and categorized per the Asia-Pacific classification as overweight (23.0–24.9 kg/m2), obesity class I (25.0–29.9 kg/m2), and obesity class II (≥30.0 kg/m2). Results: CKD developed in 34.2% of 3098 men and 34.8% of 4391 women. The mean follow-up times were 7.41 years for men and 8.25 years for women. During follow-up, the BMI distributions for men were 5.0% underweight, 43.3% normal weight, 25.6% overweight, 24.1% obesity class I, and 2.0% obesity class II; those for women were 7.7%, 50.5%, 20.5%, 18.3%, and 2.9%, respectively. Compared with normal weight, obesity class I was associated with a 6% (95% confidence interval [CI]: 2–10%) shorter time to CKD onset in men and 5% (95% CI: 2–7%) in women. In both sexes, obesity class II showed shorter survival times than normal weight by point estimates, although all 95% CIs crossed the null value. Conclusions: Obesity, as classified by the Asia-Pacific BMI system, shortened the time to CKD onset in non-diabetic Asians. The conventional BMI cutoff for obesity (≥30.0 kg/m2) may be too high to identify CKD risk in this population. The findings of this study may be useful for public health professionals in designing interventions to prevent CKD. en-copyright= kn-copyright= en-aut-name=OkawaYukari en-aut-sei=Okawa en-aut-mei=Yukari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TsudaToshihide en-aut-sei=Tsuda en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Public Health and Welfare, Zentsuji City Hall kn-affil= affil-num=2 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=body mass index kn-keyword=body mass index en-keyword=chronic kidney disease kn-keyword=chronic kidney disease en-keyword=East Asian kn-keyword=East Asian en-keyword=longitudinal studies kn-keyword=longitudinal studies en-keyword=risk factors kn-keyword=risk factors END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=1 article-no= start-page=e261 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230703 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Alcohol consumption, multiple Lugol‐voiding lesions, and field cancerization en-subtitle= kn-subtitle= en-abstract= kn-abstract=The development of multiple squamous cell carcinomas (SCC) in the upper aerodigestive tract, which includes the oral cavity, pharynx, larynx, and esophagus, is explained by field cancerization and is associated with alcohol consumption and cigarette smoking. We reviewed the association between alcohol consumption, multiple Lugol-voiding lesions, and field cancerization, mainly based on the Japan Esophageal Cohort study. The Japan Esophageal Cohort study is a prospective cohort study that enrolled patients with esophageal SCC after endoscopic resection. Enrolled patients received surveillance by gastrointestinal endoscopy every 6 months and surveillance by an otolaryngologist every 12 months. The Japan Esophageal Cohort study showed that esophageal SCC and head and neck SCC that developed after endoscopic resection for esophageal SCC were associated with genetic polymorphisms related to alcohol metabolism. They were also associated with Lugol-voiding lesions grade in the background esophageal mucosa, the score of the health risk appraisal model for predicting the risk of esophageal SCC, macrocytosis, and score on alcohol use disorders identification test. The standardized incidence ratio of head and neck SCC in patients with esophageal SCC after endoscopic resection was extremely high compared to the general population. Drinking and smoking cessation is strongly recommended to reduce the risk of metachronous esophageal SCC after treatment of esophageal SCC. Risk factors for field cancerization provide opportunities for early diagnosis and minimally invasive treatment. Lifestyle guidance of alcohol consumption and cigarette smoking for esophageal precancerous conditions, which are endoscopically visualized as multiple Lugol-voiding lesions, may play a pivotal role in decreasing the incidence and mortality of esophageal SCC. en-copyright= kn-copyright= en-aut-name=KatadaChikatoshi en-aut-sei=Katada en-aut-mei=Chikatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokoyamaTetsuji en-aut-sei=Yokoyama en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YanoTomonori en-aut-sei=Yano en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiHaruhisa en-aut-sei=Suzuki en-aut-mei=Haruhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FurueYasuaki en-aut-sei=Furue en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoKeiko en-aut-sei=Yamamoto en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DoyamaHisashi en-aut-sei=Doyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KoikeTomoyuki en-aut-sei=Koike en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TamaokiMasashi en-aut-sei=Tamaoki en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawataNoboru en-aut-sei=Kawata en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HiraoMotohiro en-aut-sei=Hirao en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OgataTakashi en-aut-sei=Ogata en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KatagiriAtsushi en-aut-sei=Katagiri en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamanouchiTakenori en-aut-sei=Yamanouchi en-aut-mei=Takenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KiyokawaHirofumi en-aut-sei=Kiyokawa en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KawakuboHirofumi en-aut-sei=Kawakubo en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KonnoMaki en-aut-sei=Konno en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YokoyamaAkira en-aut-sei=Yokoyama en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OhashiShinya en-aut-sei=Ohashi en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KondoYuki en-aut-sei=Kondo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KishimotoYo en-aut-sei=Kishimoto en-aut-mei=Yo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KanoKoichi en-aut-sei=Kano en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MureKanae en-aut-sei=Mure en-aut-mei=Kanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=HayashiRyuichi en-aut-sei=Hayashi en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=IshikawaHideki en-aut-sei=Ishikawa en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=YokoyamaAkira en-aut-sei=Yokoyama en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MutoManabu en-aut-sei=Muto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= affil-num=1 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=2 en-affil=Department of Health and Promotion, National Institute of Public Health kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East kn-affil= affil-num=4 en-affil=Endoscopy Division, National Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=6 en-affil=Division of Endoscopy, Hokkaido University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Ishikawa Prefectural Central Hospital kn-affil= affil-num=8 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=10 en-affil=Division of Endoscopy, Shizuoka Cancer Center kn-affil= affil-num=11 en-affil=Department of Surgery, National Hospital Organization Osaka National Hospital kn-affil= affil-num=12 en-affil=Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Gastroenterology, Kanagawa Cancer Center kn-affil= affil-num=14 en-affil=Department of Medicine, Division of Gastroenterology, Showa University Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Kumamoto Regional Medical Center kn-affil= affil-num=16 en-affil=Division of Gastroenterology, Department of Internal Medicine, St. Marianna University School of Medicine kn-affil= affil-num=17 en-affil=Department of Surgery, Kawasaki Municipal Kawasaki Hospital kn-affil= affil-num=18 en-affil=Department of Gastroenterology, Tochigi Cancer Center kn-affil= affil-num=19 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=20 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=21 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=22 en-affil=Department of Otolaryngology-Head and Neck Surgery, Kyoto University Hospital kn-affil= affil-num=23 en-affil=Department of Otorhinolaryngology-Head and Neck Surgery, Kitasato University School of Medicine kn-affil= affil-num=24 en-affil=Department of Public Health, Wakayama Medical University School of Medicine kn-affil= affil-num=25 en-affil=Department of Head and Neck Surgery, National Cancer Center Hospital East kn-affil= affil-num=26 en-affil=Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine kn-affil= affil-num=27 en-affil=Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center kn-affil= affil-num=28 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= en-keyword=alcohol kn-keyword=alcohol en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=field cancerization kn-keyword=field cancerization en-keyword=head and neck cancer kn-keyword=head and neck cancer en-keyword=JEC study kn-keyword=JEC study END start-ver=1.4 cd-journal=joma no-vol=52 cd-vols= no-issue=8 article-no= start-page=e18026 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Commissioning of respiratory‐gated 4D dynamic dose calculations for various gating widths without spot timestamp in proton pencil beam scanning en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Proton pencil beam scanning (PBS) is susceptible to dose degradation because of interplay effects on moving targets. For cases of unacceptable motion, respiratory-gated (RG) irradiation is an effective alternative to free breathing (FB) irradiation. However, the introduction of RG irradiation with larger gate widths (GW) is hindered by interplay effects, which are analogous to those observed with FB irradiation. Accurate estimation of interplay effects can be performed by recording spot timestamps. However, our machine lacks this feature, making it imperative to find an alternative approach. Thus, we developed an RG 4-dimensional dynamic dose (RG-4DDD) system without spot timestamps.
Purpose: This study aimed to investigate the accuracy of calculated doses from the RG-4DDD system for PBS plans with varying breathing curves, amplitudes, and periods for 10%–50% GW.
Methods: RG-4DDDs were reconstructed using in-house developed software that assigned timestamps to individual spots, integrated start times for spills with breathing curves, and utilized deformable registrations for dose accumulation. Three cubic verification plans were created using a heterogeneous phantom. Additionally, typical liver and lung cases were employed for patient plan validation. Single- and multi-field-optimized (SFO and IMPT) plans (ten beams in total) were created for the liver and lung cases in a homogeneous phantom. Lateral profile measurements were obtained under both motion and no-motion conditions using a 2D ionization chamber array (2D-array) and EBT3 Gafchromic films on the CIRS dynamic platform. Breathing curves from the cubic plans were used to assess nine patterns of sine curves, with amplitudes of 5.0–10.0 mm (10.0–20.0 mm target motions) and periods of 3–6 sec. Patient field verifications were conducted using a representative patient curve with an average amplitude of 6.4 mm and period of 3.2 sec. Additional simulations were performed assuming a ± 10% change in assigned timestamps for the dose rate (DR), spot spill (0.08-s), and gate time delay (0.1-s) to evaluate the effect of parameter selection on our 4DDD models. The 4DDDs were compared with measured values using the 2D gamma index and absolute doses over that required for dosing 95% of the target.
Results: The 2D-array measurements showed that average gamma scores for the reference (no motion) and 4DDD plans for all GWs were at least 99.9 ± 0.2% and 98.2 ± 2.4% at 3%/3 mm, respectively. The gamma scores of the 4DDDs in film measurements exceeded 95.4% and 92.9% at 2%/2 mm for the cubic and patient plans, respectively. The 4DDD calculations were acceptable under DR changes of ±10% and both spill and gate time delays of ±0.18 sec. For the 4DDD plan using all GWs for all measurement points, the absolute point differences for all validation plans were within ±5.0% for 99.1% of the points.
Conclusions: The RG-4DDD calculations (less than 50% GW) of the heterogeneous and actual patient plans showed good agreement with measurements for various breathing curves in the amplitudes and periods described above. The proposed system allows us to evaluate actual RG irradiation without requiring the ability to record spot timestamps. en-copyright= kn-copyright= en-aut-name=TominagaYuki en-aut-sei=Tominaga en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WakisakaYushi en-aut-sei=Wakisaka en-aut-mei=Yushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatoTakahiro en-aut-sei=Kato en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IchiharaMasaya en-aut-sei=Ichihara en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YasuiKeisuke en-aut-sei=Yasui en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SasakiMotoharu en-aut-sei=Sasaki en-aut-mei=Motoharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OitaMasataka en-aut-sei=Oita en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishioTeiji en-aut-sei=Nishio en-aut-mei=Teiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Radiotherapy, Medical Co. Hakuhokai, Osaka Proton Therapy Clinic kn-affil= affil-num=2 en-affil=Department of Radiotherapy, Medical Co. Hakuhokai, Osaka Proton Therapy Clinic kn-affil= affil-num=3 en-affil=Department of Radiological Sciences, School of Health Sciences, Fukushima Medical University kn-affil= affil-num=4 en-affil=Medical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of Osaka kn-affil= affil-num=5 en-affil=School of Medical Sciences, Fujita Health University kn-affil= affil-num=6 en-affil=Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=7 en-affil=Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Medical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of Osaka kn-affil= en-keyword=4D dynamic dose kn-keyword=4D dynamic dose en-keyword=interplay effect kn-keyword=interplay effect en-keyword=pencil beam scanning kn-keyword=pencil beam scanning en-keyword=proton therapy kn-keyword=proton therapy en-keyword=respiratory gating kn-keyword=respiratory gating END start-ver=1.4 cd-journal=joma no-vol=54 cd-vols= no-issue=8 article-no= start-page=afaf224 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oestrogen replacement combined with resistance exercise in older women with knee osteoarthritis: a randomised, double-blind, placebo-controlled clinical trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Interventions targeting physical function decline in older women with knee osteoarthritis (KOA) are vital for healthy ageing. The additive benefits of combining oestrogen replacement therapy (ERT) with resistance exercise remain unclear.
Objective: To evaluate the additive effect of low-dose ERT on physical performance when combined with a muscle resistance exercise programme (MREP) in older women with KOA.
Design: This is a placebo-controlled, double-blind, randomised clinical trial.
Subjects: The subjects were community-dwelling women aged ≥65 years with chronic knee pain and KOA diagnosis.
Methods: Participants completed a 3-month MREP and were randomised to receive daily low-dose transdermal ERT (oestradiol 0.54 mg/day) or placebo. Outcomes were assessed at baseline, postintervention and 12 months later. The primary outcome was change in 30-second chair stand test (CS-30) score. Secondary outcomes included muscle mass, knee extension strength, walking performance, metabolic indicators, knee pain scale and 12-item short-form health survey (SF-12). Between-group differences in CS-30 changes were analysed using a linear regression model based on the intention-to-treat principle.
Results: Among 168 individuals screened, 75 participants (mean age 73.8 years, SD 5.8) were enrolled and randomised into an ERT group (n = 37) or a placebo group (n = 38). Baseline CS-30 scores were 14.81 (SD 3.95) in the ERT group and 15.58 (SD 3.48) in the placebo group. At 3 months, mean changes were 2.59 (SD 2.58) and 1.79 (SD 2.28) repetitions, respectively. The primary analysis showed no statistically significant between-group difference [regression coefficient: 0.81 (95% CI: −0.31, 1.92); P = .16]. Post hoc subgroup and sensitivity analyses suggested that benefits may exist among early-stage KOA participants. SF-12 mental health scores also improved significantly in the ERT group. No serious adverse events occurred.
Conclusions: ERT did not confer significant additive benefits to resistance exercise overall but may improve outcomes in early-stage KOA and mental health domains. These exploratory findings warrant further investigation. en-copyright= kn-copyright= en-aut-name=MitomaTomohiro en-aut-sei=Mitoma en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OobaHikaru en-aut-sei=Ooba en-aut-mei=Hikaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiKasumi en-aut-sei=Takahashi en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoTsunemasa en-aut-sei=Kondo en-aut-mei=Tsunemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkedaTomohiro en-aut-sei=Ikeda en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakamotoYoko en-aut-sei=Sakamoto en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MakiJota en-aut-sei=Maki en-aut-mei=Jota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Medical Development Field, Center for Innovative Clinical Medicine, Okayama University kn-affil= affil-num=2 en-affil=Medical Development Field, Center for Innovative Clinical Medicine, Okayama University kn-affil= affil-num=3 en-affil=Obstetrics and Gynecology, Ochiai Hospital kn-affil= affil-num=4 en-affil=Obstetrics and Gynecology, Ochiai Hospital kn-affil= affil-num=5 en-affil=Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Medical Development Field, Center for Innovative Clinical Medicine, Okayama University kn-affil= affil-num=7 en-affil=Medical Development Field, Center for Innovative Clinical Medicine, Okayama University kn-affil= affil-num=8 en-affil=Medical Development Field, Center for Innovative Clinical Medicine, Okayama University kn-affil= en-keyword=oestrogen replacement therapy kn-keyword=oestrogen replacement therapy en-keyword=muscle resistance exercise kn-keyword=muscle resistance exercise en-keyword=knee osteoarthritis kn-keyword=knee osteoarthritis en-keyword=physical performance kn-keyword=physical performance en-keyword=randomised controlled trial kn-keyword=randomised controlled trial en-keyword=older people kn-keyword=older people END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=77 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of amyloid and tau positivity on longitudinal brain atrophy in cognitively normal individuals en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Individuals on the preclinical Alzheimer's continuum, particularly those with both amyloid and tau positivity (A + T +), display a rapid cognitive decline and elevated disease progression risk. However, limited studies exist on brain atrophy trajectories within this continuum over extended periods.
Methods This study involved 367 ADNI participants grouped based on combinations of amyloid and tau statuses determined through cerebrospinal fluid tests. Using longitudinal MRI scans, brain atrophy was determined according to the whole brain, lateral ventricle, and hippocampal volumes and cortical thickness in AD-signature regions. Cognitive performance was evaluated with the Preclinical Alzheimer's Cognitive Composite (PACC). A generalized linear mixed-effects model was used to examine group × time interactions for these measures. In addition, progression risks to mild cognitive impairment (MCI) or dementia were compared among the groups using Cox proportional hazards models.
Results A total of 367 participants (48 A + T + , 86 A + T − , 63 A − T + , and 170 A − T − ; mean age 73.8 years, mean follow-up 5.1 years, and 47.4% men) were included. For the lateral ventricle and PACC score, the A + T − and A + T + groups demonstrated statistically significantly greater volume expansion and cognitive decline over time than the A − T − group (lateral ventricle: β = 0.757 cm3/year [95% confidence interval 0.463 to 1.050], P < .001 for A + T − , and β = 0.889 cm3/year [0.523 to 1.255], P < .001 for A + T + ; PACC: β =  − 0.19 /year [− 0.36 to − 0.02], P = .029 for A + T − , and β =  − 0.59 /year [− 0.80 to − 0.37], P < .001 for A + T +). Notably, the A + T + group exhibited additional brain atrophy including the whole brain (β =  − 2.782 cm3/year [− 4.060 to − 1.504], P < .001), hippocampus (β =  − 0.057 cm3/year [− 0.085 to − 0.029], P < .001), and AD-signature regions (β =  − 0.02 mm/year [− 0.03 to − 0.01], P < .001). Cox proportional hazards models suggested an increased risk of progressing to MCI or dementia in the A + T + group versus the A − T − group (adjusted hazard ratio = 3.35 [1.76 to 6.39]).
Conclusions In cognitively normal individuals, A + T + compounds brain atrophy and cognitive deterioration, amplifying the likelihood of disease progression. Therapeutic interventions targeting A + T + individuals could be pivotal in curbing brain atrophy, cognitive decline, and disease progression. en-copyright= kn-copyright= en-aut-name=FujishimaMotonobu en-aut-sei=Fujishima en-aut-mei=Motonobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawasakiYohei en-aut-sei=Kawasaki en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=MatsudaHiroshi en-aut-sei=Matsuda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Radiology, Kumagaya General Hospital kn-affil= affil-num=2 en-affil=Department of Biostatistics, Graduate School of Medicine, Saitama Medical University kn-affil= affil-num=3 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Biofunctional Imaging, Fukushima Medical University kn-affil= en-keyword=Preclinical kn-keyword=Preclinical en-keyword=Alzheimer’s disease kn-keyword=Alzheimer’s disease en-keyword=Longitudinal MRI kn-keyword=Longitudinal MRI en-keyword=Tau kn-keyword=Tau en-keyword=Amyloid-β kn-keyword=Amyloid-β END start-ver=1.4 cd-journal=joma no-vol=207 cd-vols= no-issue= article-no= start-page=108683 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Intracranial activity of sotorasib vs docetaxel in pretreated KRAS G12C-mutated advanced non-small cell lung cancer from a global, phase 3, randomized controlled trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: To assess the efficacy and safety of sotorasib in patients with brain metastases using data from the phase 3 CodeBreaK 200 study, which evaluated sotorasib in adults with pretreated advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC).
Materials and methods: Patients with KRAS G12C-mutated NSCLC who progressed after platinum-based chemotherapy and checkpoint inhibitor therapy were randomized 1:1 to sotorasib or docetaxel. An exploratory post-hoc analysis evaluated central nervous system (CNS) progression-free survival (PFS) and time to CNS progression in patients with treated and stable brain metastases at baseline. Measures were assessed by blinded independent central review per study-modified Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.
Results: Of the patients randomly assigned to receive sotorasib (n=171) or docetaxel (n=174), baseline CNS metastases were present in 40 (23%) and 29 (17%) patients, respectively. With a median follow-up of 20.0 months for this patient subgroup, median CNS PFS was longer with sotorasib compared with docetaxel (9.6 vs 4.5 months; hazard ratio, 0.43 [95% CI, 0.20–0.92]; P=0.02). Among patients with baseline treated CNS lesions of ≥10 mm, the percentage of patients who achieved CNS tumor shrinkage of ≥30% was two-fold higher with sotorasib than docetaxel (33.3% vs 15.4%). Treatment-related adverse events among patients with CNS lesions at baseline were consistent with those of the overall study population.
Conclusions: These results suggest intracranial activity with sotorasib complements the overall PFS benefit observed with sotorasib vs docetaxel, with safety outcomes similar to those in the general CodeBreaK 200 population.
Clinical trials registration number: NCT04303780. en-copyright= kn-copyright= en-aut-name=DingemansAnne-Marie C. en-aut-sei=Dingemans en-aut-mei=Anne-Marie C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SyrigosKonstantinos en-aut-sei=Syrigos en-aut-mei=Konstantinos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiviLorenzo en-aut-sei=Livi en-aut-mei=Lorenzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PaulusAstrid en-aut-sei=Paulus en-aut-mei=Astrid kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimSang-We en-aut-sei=Kim en-aut-mei=Sang-We kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ChenYuanbin en-aut-sei=Chen en-aut-mei=Yuanbin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FelipEnriqueta en-aut-sei=Felip en-aut-mei=Enriqueta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=GriesingerFrank en-aut-sei=Griesinger en-aut-mei=Frank kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ZalcmanGerard en-aut-sei=Zalcman en-aut-mei=Gerard kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HughesBrett G.M. en-aut-sei=Hughes en-aut-mei=Brett G.M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SørensenJens Benn en-aut-sei=Sørensen en-aut-mei=Jens Benn kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=BlaisNormand en-aut-sei=Blais en-aut-mei=Normand kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FerreiraCarlos G.M. en-aut-sei=Ferreira en-aut-mei=Carlos G.M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=LindsayColin R. en-aut-sei=Lindsay en-aut-mei=Colin R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=DziadziuszkoRafal en-aut-sei=Dziadziuszko en-aut-mei=Rafal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=WardPatrick J. en-aut-sei=Ward en-aut-mei=Patrick J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ObiozorCynthia Chinedu en-aut-sei=Obiozor en-aut-mei=Cynthia Chinedu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=WangYang en-aut-sei=Wang en-aut-mei=Yang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=PetersSolange en-aut-sei=Peters en-aut-mei=Solange kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Erasmus MC Cancer Institute, University Medical Center kn-affil= affil-num=2 en-affil=Sotiria General Hospital kn-affil= affil-num=3 en-affil=Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, University of Florence kn-affil= affil-num=4 en-affil=Centre Hospitalier Universitaire de Liège kn-affil= affil-num=5 en-affil=Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine kn-affil= affil-num=6 en-affil=The Cancer & Hematology Centers of Western Michigan kn-affil= affil-num=7 en-affil=Medical Oncology Department, Vall d’Hebron University Hospital kn-affil= affil-num=8 en-affil=Pius-Hospital Oldenburg kn-affil= affil-num=9 en-affil=Okayama University Hospital kn-affil= affil-num=10 en-affil=Hospital Bichat-Claude Bernard kn-affil= affil-num=11 en-affil=The Prince Charles Hospital, University of Queensland kn-affil= affil-num=12 en-affil=Rigshospitalet kn-affil= affil-num=13 en-affil=Department of Medicine, Centre Hospitalier de l’Université de Montréal kn-affil= affil-num=14 en-affil=Oncoclinicas kn-affil= affil-num=15 en-affil=Division of Cancer Sciences, University of Manchester and The Christie NHS Foundation Trust kn-affil= affil-num=16 en-affil=University Clinical Centre, Medical University of Gdansk kn-affil= affil-num=17 en-affil=SCRI at OHC kn-affil= affil-num=18 en-affil=Amgen Inc. kn-affil= affil-num=19 en-affil=Amgen Inc. kn-affil= affil-num=20 en-affil=Lausanne University Hospital kn-affil= en-keyword=Brain metastases kn-keyword=Brain metastases en-keyword=KRAS G12C-mutated kn-keyword=KRAS G12C-mutated en-keyword=Non-small cell lung cancer kn-keyword=Non-small cell lung cancer en-keyword=NSCLC kn-keyword=NSCLC en-keyword=Randomized controlled trial kn-keyword=Randomized controlled trial en-keyword=Sotorasib kn-keyword=Sotorasib en-keyword=Survival kn-keyword=Survival END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250802 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Berberine Prevents NSAID-Induced Small Intestinal Injury by Protecting Intestinal Barrier and Inhibiting Inflammasome-Associated Activation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Nonsteroidal anti-inflammatory drugs (NSAID), which are commonly used to manage pain and inflammation, often cause gastrointestinal injuries, including small intestinal damage. Berberine (BBR) is a traditional Chinese medicine that protects against these injuries. However, the mechanism of action is not fully understood.
Aims This study aimed to evaluate the protective effects of BBR against NSAID-induced intestinal injury and elucidate the underlying molecular mechanisms.
Methods We evaluated the effects of BBR on NSAID-induced intestinal injury using a combination of mouse models and human gut organoids. Mice were treated with indomethacin with or without BBR to induce small intestinal injury. Human gut organoids were exposed to NSAID, with or without BBR, to assess their direct epithelial effects. Histological analyses, cytokine measurements, and Western blotting were performed to evaluate intestinal damage, tight junction integrity, and inflammasome-associated activation.
Results In NSAID-treated mice, BBR markedly reduced ulcers and adhesions and preserved ileal Claudin-1, Occludin, and Zonula Occludens-1 (ZO-1) levels. BBR inhibited both NOD-like receptor family pyrin domain-containing 6 and NOD-like receptor family caspase recruitment domain–containing protein 4 inflammasome activation, reducing Caspase-1 maturation and downstream interleukin-1β and tumor necrosis factor-α release. In human gut organoids, BBR demonstrated comparable protective effects by directly mitigating NSAID-induced epithelial barrier disruption caused by Claudin-1 and Occludin downregulation, although it did not restore ZO-1 expression.
Conclusions BBR effectively prevented NSAID-induced small intestinal injury by maintaining tight junction integrity and inhibiting inflammasome-associated activation, indicating its potential as a therapeutic agent against such damage. en-copyright= kn-copyright= en-aut-name=IshiguroMikako en-aut-sei=Ishiguro en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakaharaMasahiro en-aut-sei=Takahara en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakakiAkinobu en-aut-sei=Takaki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToyosawaJyunki en-aut-sei=Toyosawa en-aut-mei=Jyunki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AoyamaYuki en-aut-sei=Aoyama en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IgawaShoko en-aut-sei=Igawa en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamasakiYasushi en-aut-sei=Yamasaki en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=InokuchiToshihiro en-aut-sei=Inokuchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KinugasaHideaki en-aut-sei=Kinugasa en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Nonsteroidal anti-inflammatory drugs-induced small intestinal injury kn-keyword=Nonsteroidal anti-inflammatory drugs-induced small intestinal injury en-keyword=Berberine kn-keyword=Berberine en-keyword=Tight junction protein kn-keyword=Tight junction protein en-keyword=Inflammasomes kn-keyword=Inflammasomes END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The duration of prior anti-tumor necrosis factor agents is associated with the effectiveness of vedolizumab in patients with ulcerative colitis: a real-world multicenter retrospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aims Previous literature suggests that the response of patients with ulcerative colitis to vedolizumab may be affected by previous biologic therapy exposure. This real-world study evaluated vedolizumab treatment effectiveness in biologicnon-naïve patients.
Methods This was a multicenter, retrospective, observational chart review of records from 16 hospitals in Japan (December 1, 2018, to February 29, 2020). Included patients who had ulcerative colitis, were aged ≥ 20 years, and received at least 1 dose of vedolizumab. Outcomes included clinical remission rates from weeks 2 to 54 according to prior biologic exposure status and factors associated with clinical remission up to week 54.
Results A total of 370 eligible patients were included. Clinical remission rates were significantly higher in biologic-naïve (n=197) than in biologic-non-naïve (n=173) patients for weeks 2 to 54 of vedolizumab treatment. Higher clinical remission rates up to week 54 were significantly associated with lower disease severity (partial Mayo score ≤ 4, P= 0.001; albumin ≥ 3.0, P= 0.019) and the duration of prior anti-tumor necrosis factor α (anti-TNFα) therapy (P= 0.026). Patients with anti-TNFα therapy durations of < 3 months, 3 to < 12 months, and ≥ 12 months had clinical remission rates of 28.1%, 32.7%, and 60.0%, respectively (P= 0.001 across groups).
Conclusions The effectiveness of vedolizumab in biologic-non-naïve patients was significantly influenced by duration of prior anti-TNFα therapy. (Japanese Registry of Clinical Trials: jRCT-1080225363) en-copyright= kn-copyright= en-aut-name=KobayashiTaku en-aut-sei=Kobayashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisamatsuTadakazu en-aut-sei=Hisamatsu en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotoyaSatoshi en-aut-sei=Motoya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsuuraMinoru en-aut-sei=Matsuura en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujiiToshimitsu en-aut-sei=Fujii en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KunisakiReiko en-aut-sei=Kunisaki en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShibuyaTomoyoshi en-aut-sei=Shibuya en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiKen en-aut-sei=Takeuchi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasudaHiroshi en-aut-sei=Yasuda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YokoyamaKaoru en-aut-sei=Yokoyama en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakatsuNoritaka en-aut-sei=Takatsu en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaemotoAtsuo en-aut-sei=Maemoto en-aut-mei=Atsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaharaToshiyuki en-aut-sei=Tahara en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TominagaKeiichi en-aut-sei=Tominaga en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShimadaMasaaki en-aut-sei=Shimada en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KunoNobuaki en-aut-sei=Kuno en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=CavaliereMary en-aut-sei=Cavaliere en-aut-mei=Mary kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IshiguroKaori en-aut-sei=Ishiguro en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FernandezJovelle L en-aut-sei=Fernandez en-aut-mei=Jovelle L kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HibiToshifumi en-aut-sei=Hibi en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=3 en-affil=Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=6 en-affil=Inflammatory Bowel Disease Center, Yokohama City University Medical Center kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Juntendo University School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, IBD Center, Tsujinaka Hospital Kashiwanoha kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology, St. Marianna University School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=12 en-affil=Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital kn-affil= affil-num=13 en-affil=Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Saiseikai Utsunomiya Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Dokkyo Medical University kn-affil= affil-num=16 en-affil=Department of Gastroenterology, NHO Nagoya Medical Center kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Medicine, Fukuoka University Hospital kn-affil= affil-num=18 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=19 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=20 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=21 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= en-keyword=Tumor necrosis factor-alpha kn-keyword=Tumor necrosis factor-alpha en-keyword=Real-world evidence kn-keyword=Real-world evidence en-keyword=Colitis kn-keyword=Colitis en-keyword=ulcerative kn-keyword=ulcerative en-keyword=Vedolizumab kn-keyword=Vedolizumab en-keyword=Sequencing kn-keyword=Sequencing END start-ver=1.4 cd-journal=joma no-vol=40 cd-vols= no-issue=6 article-no= start-page=1435 end-page=1445 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250515 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real-World Effectiveness and Safety of Vedolizumab in Patients ≥ 70 Versus < 70 Years With Ulcerative Colitis: Multicenter Retrospective Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aim: Vedolizumab (VDZ) is often used in older patients with ulcerative colitis (UC) in clinical practice; however, real-world evidence is still limited, including in those with late-onset UC.
Methods: This post hoc analysis of a multicenter, retrospective, observational chart review, enrolling 370 patients with UC receiving VDZ between December 2018 and February 2020, compared effectiveness and safety of VDZ among patients ≥ 70 (n = 40) versus < 70 years (n = 330), and among patients ≥ 70 years with and without late-onset UC (age at disease onset: ≥ 70 [n = 13] versus < 70 years [n = 26]).
Results: There were no differences between patients ≥ 70 and < 70 years in clinical remission rates (week 6: 57.5% vs. 47.6%, p = 0.9174; week 14: 62.5% vs. 54.8%, p = 0.1317; week 54: 47.5% vs. 46.4%, p = 0.8149), primary nonresponse (10.0% vs. 15.5%, p = 0.6248), loss of response (12.5% vs. 9.4%, p = 0.5675), or overall safety. Among patients ≥ 70 years, the incidence of adverse drug reactions was numerically greater in those with concomitant corticosteroids than in those without. For older patients with and without late-onset UC, week 54 remission rates were 23.1% versus 57.7% (p = 0.0544); surgery was reported in 3/13 versus 2/26 patients and hospitalization in 5/13 versus 6/26 patients. One death was reported in patients with late-onset UC.
Conclusions: VDZ effectiveness and safety were similar in patients ≥ 70 and < 70 years; VDZ may be a suitable treatment option for patients ≥ 70 years with UC. Patients with late-onset UC tended to have more frequent surgery/hospitalization and lower effectiveness than those without, possibly necessitating greater caution when using VDZ.
Trial Registration: Japanese Registry of Clinical Trials registration number: jRCT-1080225363 en-copyright= kn-copyright= en-aut-name=HisamatsuTadakazu en-aut-sei=Hisamatsu en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiTaku en-aut-sei=Kobayashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotoyaSatoshi en-aut-sei=Motoya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiiToshimitsu en-aut-sei=Fujii en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunisakiReiko en-aut-sei=Kunisaki en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShibuyaTomoyoshi en-aut-sei=Shibuya en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuuraMinoru en-aut-sei=Matsuura en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakeuchiKen en-aut-sei=Takeuchi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasudaHiroshi en-aut-sei=Yasuda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YokoyamaKaoru en-aut-sei=Yokoyama en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakatsuNoritaka en-aut-sei=Takatsu en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaemotoAtsuo en-aut-sei=Maemoto en-aut-mei=Atsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaharaToshiyuki en-aut-sei=Tahara en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TominagaKeiichi en-aut-sei=Tominaga en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShimadaMasaaki en-aut-sei=Shimada en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KunoNobuaki en-aut-sei=Kuno en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FernandezJovelle L. en-aut-sei=Fernandez en-aut-mei=Jovelle L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HiroseLisa en-aut-sei=Hirose en-aut-mei=Lisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=IshiguroKaori en-aut-sei=Ishiguro en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=CavaliereMary en-aut-sei=Cavaliere en-aut-mei=Mary kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HibiToshifumi en-aut-sei=Hibi en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=2 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= affil-num=3 en-affil=Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=5 en-affil=Inflammatory Bowel Disease Center, Yokohama City University Medical Center kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Juntendo University School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=8 en-affil= kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, IBD Center, Tsujinaka Hospital Kashiwanoha kn-affil= affil-num=10 en-affil=Department of Gastroenterology, St. Marianna University School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=12 en-affil=Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital kn-affil= affil-num=13 en-affil=Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Saiseikai Utsunomiya Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Dokkyo Medical University kn-affil= affil-num=16 en-affil=Department of Gastroenterology, NHO Nagoya Medical Center kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Medicine, Fukuoka University Hospital kn-affil= affil-num=18 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=19 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=20 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=21 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=22 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= en-keyword=elderly kn-keyword=elderly en-keyword=inflammatory bowel diseases kn-keyword=inflammatory bowel diseases en-keyword=onset age kn-keyword=onset age en-keyword=vedolizumab kn-keyword=vedolizumab END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250116 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Factors affecting 1-year persistence with vedolizumab for ulcerative colitis: a multicenter, retrospective real-world study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aims The objectives of this real-world study were to determine 1-year persistence with vedolizumab in patients with ulcerative colitis and to evaluate factors contributing to loss of response.
Methods In this multicenter, retrospective, observational chart review, patients with moderately to severely active ulcerative colitis who received ≥ 1 dose of vedolizumab in clinical practice at 16 tertiary hospitals in Japan (from December 2018 through February 2020) were enrolled.
Results Persistence with vedolizumab was 64.5% (n = 370); the median follow-up time was 53.2 weeks. Discontinuation due to loss of response among initial clinical remitters was reported in 12.5% (35/281) of patients. Multivariate analysis showed that concomitant use of tacrolimus (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.00–7.62; P= 0.050) and shorter disease duration (OR for median duration ≥ 7.8 years vs. < 7.8 years, 0.33; 95% CI, 0.13–0.82; P= 0.017) were associated with discontinuation due to loss of response. Loss of response was not associated with prior use of anti-tumor necrosis factor alpha therapy, age at the time of treatment, disease severity, or concomitant corticosteroids or immunomodulators. Of the 25 patients with disease duration < 1 year, 32.0% discontinued due to loss of response.
Conclusions Persistence with vedolizumab was consistent with previous reports. Use of tacrolimus and shorter disease duration were the main predictors of decreased persistence. en-copyright= kn-copyright= en-aut-name=KobayashiTaku en-aut-sei=Kobayashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisamatsuTadakazu en-aut-sei=Hisamatsu en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotoyaSatoshi en-aut-sei=Motoya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiiToshimitsu en-aut-sei=Fujii en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunisakiReiko en-aut-sei=Kunisaki en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShibuyaTomoyoshi en-aut-sei=Shibuya en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuuraMinoru en-aut-sei=Matsuura en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiKen en-aut-sei=Takeuchi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasudaHiroshi en-aut-sei=Yasuda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YokoyamaKaoru en-aut-sei=Yokoyama en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakatsuNoritaka en-aut-sei=Takatsu en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaemotoAtsuo en-aut-sei=Maemoto en-aut-mei=Atsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaharaToshiyuki en-aut-sei=Tahara en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TominagaKeiichi en-aut-sei=Tominaga en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShimadaMasaaki en-aut-sei=Shimada en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KunoNobuaki en-aut-sei=Kuno en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FernandezJovelle L. en-aut-sei=Fernandez en-aut-mei=Jovelle L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IshiguroKaori en-aut-sei=Ishiguro en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=CavaliereMary en-aut-sei=Cavaliere en-aut-mei=Mary kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=DeguchiHisato en-aut-sei=Deguchi en-aut-mei=Hisato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HibiToshifumi en-aut-sei=Hibi en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=3 en-affil=Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=5 en-affil=Inflammatory Bowel Disease Center, Yokohama City University Medical Center kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Juntendo University School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, IBD Center kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology, St. Marianna University School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=12 en-affil=Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital kn-affil= affil-num=13 en-affil=Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Saiseikai Utsunomiya Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Dokkyo Medical University kn-affil= affil-num=16 en-affil=Department of Gastroenterology, NHO Nagoya Medical Center kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Medicine, Fukuoka University Hospital kn-affil= affil-num=18 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=19 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=20 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=21 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=22 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= en-keyword=Colitis, ulcerative kn-keyword=Colitis, ulcerative en-keyword=Inflammatory bowel diseases kn-keyword=Inflammatory bowel diseases en-keyword=Japan kn-keyword=Japan en-keyword=Vedolizumab kn-keyword=Vedolizumab en-keyword=Medication persistence kn-keyword=Medication persistence END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=7 article-no= start-page=920 end-page=927 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The association of fasting triglyceride variability with renal dysfunction and proteinuria in medical checkup participants en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The association between the variability of triglyceride (TG) and chronic kidney disease (CKD) progression remains unclear. We examined whether intraindividual variability in fasting TG was associated with the exacerbation of CKD.
Methods We conducted a retrospective and observational study. 18,339 participants, who went through medical checkups and had checked their estimated glomerular filtration rate (eGFR) and semi-quantitative proteinuria by urine dipstick every year since 2017 for 4 years were registered. Variability in fasting TG was determined using the standard deviation (SD), and maximum minus minimum difference (MMD) between 2017 and 2021. The primary end point for the analysis of eGFR decline was eGFR < 60 mL/min/1.73 m2. The secondary end point for the analysis of proteinuria was the incidence of proteinuria ≥ ( ±) by urine dipstick.
Results The renal survival was lower in the higher-SD, and higher-MMD groups than in the lower-SD, and lower-MMD groups, respectively (log-rank test p < 0.001, and < 0.001, respectively). Lower SD and lower MMD were significantly associated with renal survival in the adjusted model (hazard ratio (HR), 1.12; 95% confidence intervals (CI), 1.04–1.21, and HR, 1.13; 95% CI 1.05–1.23, respectively). The non-incidence of proteinuria was lower in the higher-SD, and higher-MMD groups than in the lower-SD, and lower-MMD groups, respectively (log-rank test p < 0.001 and < 0.001, respectively).
Conclusion Fasting TG variability was associated with CKD progression in participants who went through medical checkups. en-copyright= kn-copyright= en-aut-name=Matsuoka-UchiyamaNatsumi en-aut-sei=Matsuoka-Uchiyama en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsakawaTomohiko en-aut-sei=Asakawa en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakurabuYoshimasa en-aut-sei=Sakurabu en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatayamaKatsuyoshi en-aut-sei=Katayama en-aut-mei=Katsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkamotoShugo en-aut-sei=Okamoto en-aut-mei=Shugo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OnishiYasuhiro en-aut-sei=Onishi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaKeiko en-aut-sei=Tanaka en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakeuchiHidemi en-aut-sei=Takeuchi en-aut-mei=Hidemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakemotoRika en-aut-sei=Takemoto en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UmebayashiRyoko en-aut-sei=Umebayashi en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=eGFR decline kn-keyword=eGFR decline en-keyword=Proteinuria kn-keyword=Proteinuria en-keyword=Renal dysfunction kn-keyword=Renal dysfunction en-keyword=Triglyceride variability kn-keyword=Triglyceride variability en-keyword=Fasting triglyceride kn-keyword=Fasting triglyceride END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=311 end-page=315 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=Mimicking Contralateral Pneumothorax during Thoracoscopic Bullectomy Associated with Intraoperative Hyperinflation of a Large Bulla in an Obese Patient en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 55-year-old obese Japanese male with left pneumothorax presented to our hospital. Bilateral pulmonary emphysema was confirmed. Persistent air leakage was observed, and a thoracoscopic bullectomy was performed. Although the thoracoscopic bullectomy was completed uneventfully, pre-extubation chest X-ray imaging indicated hyper-lucency occupying the right upper part of the thoracic cavity, suggesting right-sided pneumothorax. CT imaging indicated a right-upper-lobe expanded bulla. Extubation was performed, and the hyperinflated bulla gradually deflated. Careful management of bulla expansion and respiratory status may be necessary for patients with obesity and large bullae, especially in one-lung ventilation cases. en-copyright= kn-copyright= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiranoYutaka en-aut-sei=Hirano en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= en-keyword=giant bulla kn-keyword=giant bulla en-keyword=pneumothorax kn-keyword=pneumothorax en-keyword=obesity kn-keyword=obesity en-keyword=positive pressure ventilation kn-keyword=positive pressure ventilation en-keyword=one lung ventilation kn-keyword=one lung ventilation END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=299 end-page=303 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=Pulmonary Calcium Phosphate Cement Embolism After Percutaneous Vertebroplasty for Thoracic Vertebrae Fractures en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pulmonary cement embolism (PCE) is a rare but severe complication following percutaneous vertebroplasty (PVP). Calcium phosphate cement (CPC) has emerged as an alternative to traditional materials for vertebral augmentation. There appear to be no established guidelines for managing symptomatic PCE, and there is scarce literature on CPC embolisms. This is a first report of a case of pulmonary CPC embolism following PVP. The patient, a 63-year-old Chinese female, was administered anticoagulant treatment and achieved a satisfactory outcome. Her case highlights the severe potential morbidity associated with CPC leakage and emphasizes the efficacy of anticoagulant treatment for managing pulmonary CPC embolisms. en-copyright= kn-copyright= en-aut-name=FengRuibin en-aut-sei=Feng en-aut-mei=Ruibin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ZhuBikang en-aut-sei=Zhu en-aut-mei=Bikang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WeiDanyun en-aut-sei=Wei en-aut-mei=Danyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhuDingjiao en-aut-sei=Zhu en-aut-mei=Dingjiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChenCairu en-aut-sei=Chen en-aut-mei=Cairu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical University kn-affil= affil-num=2 en-affil=Department of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical University kn-affil= affil-num=3 en-affil=Department of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical University kn-affil= affil-num=4 en-affil=Department of Radiology, the Ninth Affiliated Hospital of Guangxi Medical University kn-affil= affil-num=5 en-affil=Department of Orthopedics, the Ninth Affiliated Hospital of Guangxi Medical University kn-affil= en-keyword=percutaneous vertebroplasty kn-keyword=percutaneous vertebroplasty en-keyword=thoracic vertebrae fracture kn-keyword=thoracic vertebrae fracture en-keyword=calcium phosphate cement kn-keyword=calcium phosphate cement en-keyword=pulmonary embolism kn-keyword=pulmonary embolism END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=283 end-page=286 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Anterior Uveitis Secondary to an Infected Postoperative Maxillary Cyst en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 76-year-old man presented with right eyelid swelling and deteriorated vision. Examination revealed anterior uveitis with hypopyon and a visual acuity of 20/2,000 in the right eye, with no abnormalities in the left. Computed tomography revealed enlargement of the right maxillary sinus and internal fluid accumulation, suggesting a postoperative maxillary cyst (POMC). Nasal endoscopic surgery drained the pus by opening the lower wall of the maxillary cyst. Following the procedure, intraocular inflammation resolved, and visual acuity in the right eye improved to 24/20. This is the first reported case of uveitis secondary to POMC. en-copyright= kn-copyright= en-aut-name=ImamuraYuta en-aut-sei=Imamura en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShiodeYusuke en-aut-sei=Shiode en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraShuhei en-aut-sei=Kimura en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HosokawaMio en-aut-sei=Hosokawa en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KanzakiYuki en-aut-sei=Kanzaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KindoHiroya en-aut-sei=Kindo en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MoritaTetsuro en-aut-sei=Morita en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MuraiAya en-aut-sei=Murai en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=anterior uveitis kn-keyword=anterior uveitis en-keyword=hypopyon kn-keyword=hypopyon en-keyword=maxillary sinus kn-keyword=maxillary sinus en-keyword=postoperative maxillary cyst kn-keyword=postoperative maxillary cyst END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=269 end-page=278 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=Femoral and Global Femoral Offset, but not Anteroposterior Offset, to Improve Postoperative Outcomes Following Total Hip Arthroplasty: Considerations Independent of the Contralateral Side en-subtitle= kn-subtitle= en-abstract= kn-abstract=The global femoral offset (the sum of the acetabular and femoral offsets) influences outcomes after total hip arthroplasty (THA). The optimal offset using plain radiographs has been reported, but internal and external rotations of the hip affect the offset value, producing unclear results when the nonsurgical side is not intact. We investigated the relationship between a functional hip score, i.e., the Harris Hip Score (HHS) and its effect on the post-THA anteroposterior and lateral offsets, and we sought to identify the optimal offset value. The cases of 158 patients with hemilateral hip osteoarthritis who underwent THA at a single center were retrospectively analyzed in this cross-sectional study. Three-dimensional pelvic and femoral models generated from computed tomography were used to examine several parameters, and the results revealed a significant binomial correlation among the modified HHS and femoral and global femoral offsets, with maximum values of 21.3 mm and 40 mm/100 cm body height, respectively. Pelvic and femoral parameters were measured and evaluated via alignment with a specific coordinate system. Our findings indicate that preoperative planning using these parameters may improve postoperative hip function, even when the nonoperative side is unsuitable for use as a reference, as in bilateral hip osteoarthritis cases. en-copyright= kn-copyright= en-aut-name=ImaiNorio en-aut-sei=Imai en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiranoYuki en-aut-sei=Hirano en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HommaDaisuke en-aut-sei=Homma en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EndoYuki en-aut-sei=Endo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HorigomeYoji en-aut-sei=Horigome en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiHayato en-aut-sei=Suzuki en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawashimaHiroyuki en-aut-sei=Kawashima en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=2 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=3 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=4 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=5 en-affil=Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=6 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=7 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= en-keyword=total hip arthroplasty kn-keyword=total hip arthroplasty en-keyword=global femoral offset kn-keyword=global femoral offset en-keyword=postoperative outcome kn-keyword=postoperative outcome en-keyword=three-dimensional analysis kn-keyword=three-dimensional analysis en-keyword=anteroposterior offset kn-keyword=anteroposterior offset END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=261 end-page=267 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=Outcome of Decompression Surgery Following Rapid Neurological Deterioration in Patients with Spinal Cord Injury Without Radiographic Evidence of Trauma (SCIWORET) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cervical spondylotic myelopathy (CSM) and ossification of the posterior longitudinal ligament (OPLL) increase the likelihood of spinal cord injury without radiographic evidence of trauma (SCIWORET). Opinions regarding the optimal timing for surgery in such cases vary, however. We retrospectively investigated the demographics and outcomes of patients with SCIWORET who underwent surgery shortly after experiencing rapid neurological deterioration, and we matched patients who underwent standby surgery for CSM or OPLL. Although the optimal timing of surgery for SCIWORET remains unclear, our findings suggest that early stage surgery for SCIWORET may yield favorable neurological improvements. en-copyright= kn-copyright= en-aut-name=HirataYuichi en-aut-sei=Hirata en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugaharaChiaki en-aut-sei=Sugahara en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SasadaSusumu en-aut-sei=Sasada en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyakeHayato en-aut-sei=Miyake en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagaseTakayuki en-aut-sei=Nagase en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=spinal trauma kn-keyword=spinal trauma en-keyword=SCIWORET kn-keyword=SCIWORET en-keyword=timing of surgery kn-keyword=timing of surgery en-keyword=cervical spondylotic myelopathy kn-keyword=cervical spondylotic myelopathy en-keyword=ossification of the posterior longitudinal ligament kn-keyword=ossification of the posterior longitudinal ligament END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=253 end-page=259 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Study of Periprosthetic Femoral Stem Fractures in Hip Arthroplasty for Femoral Neck Fracture en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study investigated the risk factors for bone fragility and perioperative periprosthetic femoral stem fractures in patients undergoing hip arthroplasty for femoral neck fractures. The records of 215 patients (42 male, 173 female; mean age, 84.4 years) were analyzed to assess correlations among periprosthetic fracture rates and sex, age, body mass index (BMI), Dorr classification, femoral stem fixation type (cemented/cementless), and bone mineral density (BMD) of the contralateral proximal femur. The overall prevalence of perioperative periprosthetic fractures was 4.7%. All patients with periprosthetic fractures were female, and all but one were ≥ 80 years of age. Fracture rates were higher in patients with lower BMI, although this difference was not significant. The fracture rates were 0%, 4.7%, and 7.9% for Dorr types A, B, and C, respectively, and 0% and 5.3% for patients who received cemented and cementless stems, respectively. The findings indicated that female patients, those of advanced age, those with lower BMI, and those with Dorr type C had lower BMDs. Although BMD was significantly lower in patients who received cemented stems compared to those who received cementless stems, no fractures were observed in the former group, suggesting that the use of cemented stems is safe for this high-risk population. en-copyright= kn-copyright= en-aut-name=MiyakeYoshiaki en-aut-sei=Miyake en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakagiToru en-aut-sei=Takagi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KonishiikeTaizo en-aut-sei=Konishiike en-aut-mei=Taizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital kn-affil= en-keyword=bone mineral density kn-keyword=bone mineral density en-keyword=cemented stem kn-keyword=cemented stem en-keyword=Dorr classification kn-keyword=Dorr classification en-keyword=femoral neck fracture kn-keyword=femoral neck fracture en-keyword=periprosthetic femoral stem fracture kn-keyword=periprosthetic femoral stem fracture END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=231 end-page=242 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bloodstream Infections Caused by Gram-Negative Bacteria in Geriatric Patients: Epidemiology, Antimicrobial Resistance and The Factors Affecting Mortality en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bloodstream infections (BSIs) are an important cause of morbidity and mortality in geriatric patients. We retrospectively analyzed the cases of geriatric patients who developed BSIs due to gram-negative bacteria in order to evaluate the epidemiology, antimicrobial resistance, and the factors affecting mortality. The cases of 110 patients aged ≥ 65 years admitted to our hospital between January 1, 2017, and December 31, 2022 were assessed; 70 (63.6%) of the BSIs were healthcare-associated BSIs. The urinary system was the most common detectable source of infection at 43.6%. The most frequently isolated bacteria were Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, in that order. Carbapenem resistance was detected in 17 patients (15.5%), and extended-spectrum beta-lactamase (ESBL) production from Enterobacterales family members was detected in 37 (51.4%) patients. Multivariate analysis revealed that (i) the probability of mortality in the patients with total bilirubin was increased by approx. sixfold and (ii) the likelihood of mortality for those with a Pitt bacteremia score (PBS) ≥ 4 points was approx. 17 times higher. PBS and simplified qPitt scores can help predict mortality and manage geriatric patients. There is a significant increase in mortality among patients with procalcitonin (PCT) levels at ≥ 2 nm/ml. en-copyright= kn-copyright= en-aut-name=KardanM Enes en-aut-sei=Kardan en-aut-mei=M Enes kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ErdemIlknur en-aut-sei=Erdem en-aut-mei=Ilknur kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YildizEmre en-aut-sei=Yildiz en-aut-mei=Emre kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KirazNuri en-aut-sei=Kiraz en-aut-mei=Nuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ÇelikkolAliye en-aut-sei=Çelikkol en-aut-mei=Aliye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Faculty of Medicine, Namik Kemal University kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Faculty of Medicine, Namik Kemal University kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Faculty of Medicine, Namik Kemal University kn-affil= affil-num=4 en-affil=Department of Medical Microbiology, Faculty of Medicine, Namik Kemal University kn-affil= affil-num=5 en-affil=Department of Biochemistry, Faculty of Medicine, Namik Kemal University kn-affil= en-keyword=geriatrics kn-keyword=geriatrics en-keyword=gram-negative bacteria kn-keyword=gram-negative bacteria en-keyword=epidemiology kn-keyword=epidemiology en-keyword=antimicrobial resistance kn-keyword=antimicrobial resistance en-keyword=mortality kn-keyword=mortality END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=221 end-page=229 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=Organ Donation after Extracorporeal Cardiopulmonary Resuscitation: Clinical and Ethical Perspectives en-subtitle= kn-subtitle= en-abstract= kn-abstract=Extracorporeal cardiopulmonary resuscitation (ECPR) has evolved into a life-saving therapy for select cardiac arrest patients, yet a growing body of evidence suggests it also holds promise as a bridge to organ donation in non-survivors. This review explores the clinical outcomes, ethical complexities, and evolving policies surrounding organ donation after ECPR. We summarize recent international and Japanese data demonstrating favorable graft function from ECPR donors, with the exception of lung transplantation. The ethical challenges — particularly those involving brain death determination on extracorporeal membrane oxygenation and adherence to the dead donor rule — are discussed in the context of Japan’s recent regulatory reforms. Additionally, we highlight the importance of structured end-of-life communication through multidisciplinary team meetings in facilitating ethically sound transitions from rescue efforts to donation pathways. Moving forward, improvements in donor management, standardized legal frameworks, and public and professional education are essential to optimizing the life-saving and life-giving potential of ECPR. 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=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=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=KosakiYoshinori en-aut-sei=Kosaki en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AgetaKohei en-aut-sei=Ageta en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=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=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=brain death kn-keyword=brain death en-keyword=end-of-life care kn-keyword=end-of-life care en-keyword=ethical dilemmas kn-keyword=ethical dilemmas en-keyword=extracorporeal cardiopulmonary resuscitation kn-keyword=extracorporeal cardiopulmonary resuscitation 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=20250605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Determinants of residual myometrial thickness after cesarean delivery: Comparative analysis of barbed versus conventional sutures—A sub‐analysis from the SPIRAL trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: This sub-analysis aimed to determine whether conventional suture-associated risk factors for cesarean scar defect show similar outcomes with barbed continuous suturing, and to identify factors influencing residual myometrial thickness when using barbed continuous sutures.
Methods: This sub-analysis of a multicenter, parallel-group, randomized controlled trial across four Japanese obstetrics and gynecology departments included 1211 women who had their first cesarean delivery between May 2020 and March 2023. Among them, 298 women underwent a C-section, with 253 follow-up through July 2023. Singleton pregnancies were randomly assigned to receive either barbed or conventional double-layered continuous sutures in a 1:1 ratio; they were monitored from consent through their 6- to 7-month check-up. The effects of cervical ripening, facility characteristics, and surgeon experience were investigated using a two-way ANOVA.
Results: Of the remaining 253 patients, 33 were lost to follow-up and 220 completed follow-up (110 per group). One institution enrolled the largest proportion of participants (45.9%), whereas two other institutions had more experienced surgeons. Two-way ANOVA revealed that surgeon experience (P = 0.020) and institutional factors (P < 0.001) significantly influenced the residual myometrial thickness at 6–7 months after surgery, whereas cervical dilation during active labor did not (P = 0.215). Additionally, a significant interaction was observed between institutional factors and suture type (barbed vs. conventional) on residual myometrial thickness (Pinteraction <0.001).
Conclusion: Institutional factors and surgeon experience represent significant determinants of residual myometrial thickness when using barbed sutures for cesarean closure, highlighting the importance of standardized surgical protocols and training across facilities. en-copyright= kn-copyright= en-aut-name=MakiJota en-aut-sei=Maki en-aut-mei=Jota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OobaHikaru en-aut-sei=Ooba en-aut-mei=Hikaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitomaTomohiro en-aut-sei=Mitoma en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakatoHikari en-aut-sei=Nakato en-aut-mei=Hikari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuemoriAyano en-aut-sei=Suemori en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuriyamaChiaki en-aut-sei=Kuriyama en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakataShujiro en-aut-sei=Sakata en-aut-mei=Shujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MishimaSakurako en-aut-sei=Mishima en-aut-mei=Sakurako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OhiraAkiko en-aut-sei=Ohira en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EtoEriko en-aut-sei=Eto en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, 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 Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=barbed suture kn-keyword=barbed suture en-keyword=cervical ripening kn-keyword=cervical ripening en-keyword=cesarean scar defect kn-keyword=cesarean scar defect en-keyword=cesarean scar disorder kn-keyword=cesarean scar disorder en-keyword=niche kn-keyword=niche en-keyword=residual myometrial thickness kn-keyword=residual myometrial thickness en-keyword=risk factors kn-keyword=risk factors END start-ver=1.4 cd-journal=joma no-vol=104 cd-vols= no-issue=2 article-no= start-page=151495 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tri-culture model of intestinal epithelial cell, macrophage, and bacteria for the triggering of inflammatory bowel disease on a microfluidic device en-subtitle= kn-subtitle= en-abstract= kn-abstract=Inflammatory bowel disease (IBD) involves gastrointestinal inflammation, due to intestinal epithelial barrier destruction caused by excessive immune activation. Conventional cell culture systems do not provide a model system that can recapitulate the complex interactions between epithelial cells, immune cells, and intestinal bacteria. To address this, we developed a microfluidic device that mimics the inflammatory response associated with microbial invasion of the intestinal mucosa. The device consisted of two media channels, an upper and a lower channel, and a porous membrane between these channels on which C2BBe1 intestinal epithelial cells were seeded to form a tight junction layer. Each electrode was placed in contact with both channels to continuously monitor the tight junction state. Fresh medium flow allowed bacterial numbers to be controlled and bacterial toxins to be removed, allowing co-culture of mammalian cells and bacteria. In addition, RAW264 macrophage cells were attached to the bottom of the lower channel. By introducing E. coli into the lower channel, the RAW264 cells were activated and produced TNF-α, successfully recapitulating a culture model of inflammation in which the C2BBe1cell tight junction layer was destroyed. The main structure of the device was initially made of polydimethylsiloxane to facilitate its widespread use, but with a view to introducing anaerobic bacteria in the future, a similar phenomenon was successfully reproduced using polystyrene. When TPCA-1, an IκB kinase 2 inhibitor was added into this IBD culture model, the tight junction destruction was significantly suppressed. The results suggest that this IBD culture model also is useful as a screening system for anti-IBD drugs. en-copyright= kn-copyright= en-aut-name=TamuraShiori en-aut-sei=Tamura en-aut-mei=Shiori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PasangClarissa Ellice Talitha en-aut-sei=Pasang en-aut-mei=Clarissa Ellice Talitha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsudaMinami en-aut-sei=Tsuda en-aut-mei=Minami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaShilan en-aut-sei=Ma en-aut-mei=Shilan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShindoHiromasa en-aut-sei=Shindo en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhkuboTomoki en-aut-sei=Ohkubo en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiyamaYoichi en-aut-sei=Fujiyama en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TamaiMiho en-aut-sei=Tamai en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TagawaYoh-ichi en-aut-sei=Tagawa en-aut-mei=Yoh-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=2 en-affil=School of Life Science and Technology, Tokyo Institute of Technology kn-affil= affil-num=3 en-affil=School of Life Science and Technology, Tokyo Institute of Technology kn-affil= affil-num=4 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=5 en-affil=School of Life Science and Technology, Tokyo Institute of Technology kn-affil= affil-num=6 en-affil=Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Biology-Chemistry Unit, Technology Research Laboratory, Shimadzu Corporation kn-affil= affil-num=8 en-affil=Biology-Chemistry Unit, Technology Research Laboratory, Shimadzu Corporation kn-affil= affil-num=9 en-affil=School of Life Science and Technology, Tokyo Institute of Technology kn-affil= affil-num=10 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= en-keyword=Intestine chip kn-keyword=Intestine chip en-keyword=Inflammatory bowel disease kn-keyword=Inflammatory bowel disease en-keyword=Co-culture kn-keyword=Co-culture en-keyword=Tri-culture kn-keyword=Tri-culture en-keyword=Fluidic device kn-keyword=Fluidic device en-keyword=Disease model kn-keyword=Disease model en-keyword=Macrophage kn-keyword=Macrophage en-keyword=Inflammation kn-keyword=Inflammation END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=15 article-no= start-page=e71098 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real‐World Data of Comprehensive Cancer Genomic Profiling Tests Performed in the Routine Clinical Setting in Sarcoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Next-generation sequencing-based comprehensive cancer genomic profiling (CGP) tests are beneficial for refining diagnosis and personalized treatment of various cancers. However, the clinical impact of CGP, as covered by public health insurance in the management of sarcomas, remains unknown. Especially, the data on the utility of the newly emerging dual DNA–RNA panel compared to the conventional DNA-only panel in clinical settings is lacking. Therefore, we evaluated the utility of CGP in routine clinical practice for sarcoma treatment.
Patients and Methods: In this study, three types of DNA panel and one DNA–RNA panel, reimbursed by Japanese public health insurance, were utilized. We detected oncogenic and druggable gene mutations and genotype-matched therapies.
Results: One hundred and thirty-six patients were included in this study. Based on the detection of highly histology-specific translocations in the sequencing results, 2.2% of patients were re-classified. In patients with translocation-related sarcomas, a DNA–RNA panel identified more histology-specific fusion genes than DNA panels (p = 0.0035). Specifically, 86.8% and 39.0% of patients had oncogenic and druggable genomic alterations, respectively. Of these, 9.6% underwent genotype-matched therapy, with a 36.3% response rate and an 81.8% disease control rate. Patients who were administered genomically matched therapy had better overall survival (OS) than those who did not in patients with metastatic or advanced sarcoma with no prior chemotherapy (3-year OS: 83.3% vs. 48.0%, p = 0.42). Patients with TP53 and RB1 mutations had worse OS than those without. Germline findings were detected in 11.0% of the patients, one of whom had a truly germline origin.
Conclusions: This study suggests that publicly reimbursed CGP tests, particularly the dual DNA–RNA panel, could be beneficial for refining diagnostic precision in selected sarcoma subtypes, treatment decisions, detecting the germline findings, and prognosis prediction in routine clinical settings for sarcoma. The implementation of genotype-matched therapies showed favorable clinical outcomes and improved the prognosis. en-copyright= kn-copyright= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OsoneTatsunori en-aut-sei=Osone en-aut-mei=Tatsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItanoTakuto en-aut-sei=Itano en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IdaNaoyuki en-aut-sei=Ida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FutagawaMashu en-aut-sei=Futagawa en-aut-mei=Mashu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShimoiTatsunori en-aut-sei=Shimoi en-aut-mei=Tatsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Medical Oncology, National Cancer Center Hospital kn-affil= affil-num=13 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Center for Clinical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=comprehensive genomic profiling kn-keyword=comprehensive genomic profiling en-keyword=genotype-matched therapy kn-keyword=genotype-matched therapy en-keyword=multiplex gene panel test kn-keyword=multiplex gene panel test en-keyword=sarcoma kn-keyword=sarcoma END start-ver=1.4 cd-journal=joma no-vol=192 cd-vols= no-issue= article-no= start-page=155 end-page=162 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=Effectiveness of exercise therapy on chemotherapy-induced peripheral neuropathy in patients with ovarian cancer: A scoping review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background & aims. Exercise therapy is a potentially beneficial treatment option for chemotherapy-induced peripheral neuropathy (CIPN). However, there is a lack of consensus on the management of CIPN in patients with ovarian cancer. The purpose of this scoping review was to evaluate the evidence on the effectiveness of exercise therapy in patients with ovarian cancer and explore key physical fitness parameters.
Methods. A systematic electronic search was conducted using the MEDLINE, CINAHL, Web of Science, PEDro, and ClinicalTrials.gov databases. Two independent reviewers summarized the features and data from the literature regarding the effectiveness of exercise therapy for CIPN and the association between CIPN and physical fitness parameters.
Results. Ten articles involving 3402 participants were reviewed. The study design included one randomized controlled trial, one single-arm trial, one prospective cohort study, five retrospective cohort studies, and two cross-sectional studies. The mean patient age was >60 years in three studies and 50–60 years in six studies. The mean body mass index was >25.0 kg/m2 in six studies and not stated in four studies. In six references, patients received platinum and taxane-based chemotherapy. The effectiveness of an exercise therapy program for CIPN was reported in a randomized controlled trial. Two cross-sectional studies highlighted the association between daily physical inactivity and CIPN; two retrospective cohort studies showed an association between low skeletal muscle density and CIPN; one article demonstrated an association between physical dysfunction and CIPN.
Conclusion. This scoping review indicates that although evidence is lacking, exercise intervention programs for CIPN in patients with ovarian cancer have potential benefits, especially when focused on daily physical activity, skeletal muscle density, and physical function. en-copyright= kn-copyright= en-aut-name=KonumaMasanori en-aut-sei=Konuma en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkedaTomohiro en-aut-sei=Ikeda en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitomaTomohiro en-aut-sei=Mitoma en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShirakawaShinsuke en-aut-sei=Shirakawa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MakiJota en-aut-sei=Maki en-aut-mei=Jota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatayamaYoshimi en-aut-sei=Katayama en-aut-mei=Yoshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HamadaMasanori en-aut-sei=Hamada en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagaoShoji en-aut-sei=Nagao en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= en-keyword=Ovarian cancer kn-keyword=Ovarian cancer en-keyword=Peripheral neuropathy kn-keyword=Peripheral neuropathy en-keyword=Sarcopenia kn-keyword=Sarcopenia en-keyword=Physical activity kn-keyword=Physical activity en-keyword=Exercise therapy kn-keyword=Exercise therapy END start-ver=1.4 cd-journal=joma no-vol=508 cd-vols= no-issue= article-no= start-page=111242 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=Enhanced aboveground biomass density estimation in Central Vietnamese forests en-subtitle= kn-subtitle= en-abstract= kn-abstract=Accurate estimation of spatially explicit forest aboveground biomass density (AGBD) is essential for supporting climate change mitigation strategies. Recent studies have demonstrated the predictive effectiveness of the random forest (RF) algorithm in forest AGBD estimation utilizing multi-source remote sensing (RS) data. However, the RF-based estimates may be further enhanced by integrating RF with kriging techniques that account for spatial autocorrelation in model residuals. Therefore, we investigated the performance of random forest ordinary kriging (RFOK) and random forest co-kriging (RFCK) for estimating AGBD in Central Vietnamese forests using Advanced Land Observing Satellite-2 Phased Array L-band Synthetic Aperture Radar-2 (ALOS-2 PALSAR-2), Sentinel-1 (S1), and Sentinel-2 (S2) imageries. 277 predictors, including spectral bands, radar backscatter coefficients, vegetation indices, biophysical variables, and texture metrics, were derived from these RS datasets and statistically linked to field measurements from 104 geo-referenced forest inventory plots. The results showed that textures, modified chlorophyll absorption ratio index (MCARI), and radar backscatters were key contributors to AGBD variability. The fusion of ALOS-2 PALSAR-2 and S2 data yielded the highest RF performance, with coefficient of determination (R2), root mean square error (RMSE), and mean absolute error (MAE) achieving 0.75, 39.15 t.ha-1, and 32.20 t.ha-1, respectively. Incorporating interpolated residuals by ordinary kriging and co-kriging into RF predictions enhanced estimation accuracy, with relative improvements of 5.74–7.04 % in R2, 8.73–10.91 % in RMSE, and 13.62–15.27 % in MAE, yet these gains remained limited. Although RFOK achieved marginally better accuracy (R2 = 0.80, RMSE = 34.88 t.ha-1, MAE = 27.28 t.ha-1) compared to RFCK (R2 = 0.79, RMSE = 35.73 t.ha-1, MAE = 27.81 t.ha-1), the latter reduced estimation bias more effectively, likely due to the inclusion of elevation as a covariate in the co-kriging process. These findings underscore the potential of the hybrid RF-kriging frameworks for improving spatial AGBD estimation, offering a robust approach for carbon accounting in tropical ecosystems. en-copyright= kn-copyright= en-aut-name=HoViet Hoang en-aut-sei=Ho en-aut-mei=Viet Hoang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoritaHidenori en-aut-sei=Morita en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BachoferFelix en-aut-sei=Bachofer en-aut-mei=Felix kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HoThanh Ha en-aut-sei=Ho en-aut-mei=Thanh Ha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=German Aerospace Center (DLR), Earth Observation Center kn-affil= affil-num=4 en-affil=University of Agriculture and Forestry, Hue University kn-affil= en-keyword=Forest aboveground biomass density kn-keyword=Forest aboveground biomass density en-keyword=Random forest kn-keyword=Random forest en-keyword=Ordinary kriging kn-keyword=Ordinary kriging en-keyword=Co-kriging kn-keyword=Co-kriging en-keyword=Multispectral kn-keyword=Multispectral en-keyword=Multi-frequency synthetic aperture radar kn-keyword=Multi-frequency synthetic aperture radar END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=5 article-no= start-page=1554 end-page=1577 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250405 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparison of geostatistics, machine learning algorithms, and their hybrid approaches for modeling soil organic carbon density in tropical forests en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Understanding the spatial variability of soil organic carbon density (SOCD) in tropical forests is necessary for efficient climate change mitigation initiatives. However, accurately modeling SOCD in these landscapes is challenging due to low-density sampling efforts and the limited availability of in-situ data caused by constrained accessibility. In this study, we aimed to explore the most suitable modeling technique for SOCD estimation in the context of tropical forest ecosystems.
Methods To support the research, thirty predictor covariates derived from remote sensing data, topographic attributes, climatic factors, and geographic positions were utilized, along with 104 soil samples collected from the top 30 cm of soil in Central Vietnamese tropical forests. We compared the effectiveness of geostatistics (ordinary kriging, universal kriging, and kriging with external drift), machine learning (ML) algorithms (random forest and boosted regression tree), and their hybrid approaches (random forest regression kriging and boosted regression tree regression kriging) for the prediction of SOCD. Prediction accuracy was evaluated using the coefficient of determination (R2), the root mean squared error (RMSE), and the mean absolute error (MAE) obtained from leave-one-out cross-validation.
Results The study results indicated that hybrid approaches performed best in predicting forest SOCD with the greatest values of R2 and the lowest values of MAE and RMSE, and the ML algorithms were more accurate than geostatistics. Additionally, the prediction maps produced by the hybridization showed the most realistic SOCD pattern, whereas the kriged maps were prone to have smoother patterns, and ML-based maps were inclined to possess more detailed patterns. The result also revealed the superiority of the ML plus residual kriging approaches over the ML models in reducing the underestimation of large SOCD values in high-altitude mountain areas and the overestimation of low SOCD values in low-lying terrain areas.
Conclusion Our findings suggest that the hybrid approaches of geostatistics and ML models are most suitable for modeling SOCD in tropical forests. en-copyright= kn-copyright= en-aut-name=HoViet Hoang en-aut-sei=Ho en-aut-mei=Viet Hoang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoritaHidenori en-aut-sei=Morita en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HoThanh Ha en-aut-sei=Ho en-aut-mei=Thanh Ha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BachoferFelix en-aut-sei=Bachofer en-aut-mei=Felix kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NguyenThi Thuong en-aut-sei=Nguyen en-aut-mei=Thi Thuong 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, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=University of Agriculture and Forestry, Hue University kn-affil= affil-num=4 en-affil=German Aerospace Center (DLR), Earth Observation Center kn-affil= affil-num=5 en-affil=University of Agriculture and Forestry, Hue University kn-affil= en-keyword=Digital soil mapping kn-keyword=Digital soil mapping en-keyword=Hybrid approaches kn-keyword=Hybrid approaches en-keyword=Kriging kn-keyword=Kriging en-keyword=Machine learning kn-keyword=Machine learning en-keyword=Soil organic carbon density kn-keyword=Soil organic carbon density en-keyword=Tropical forests kn-keyword=Tropical forests END start-ver=1.4 cd-journal=joma no-vol=120 cd-vols= no-issue=1 article-no= start-page=87 end-page=98 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparable Clinical Outcomes Between Segmentectomy and Lobectomy for NSCLC With Unsuspected N1/N2: A Multicenter Real-World Data Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Segmentectomy for lung cancer has been increasingly performed. However, evidence regarding the necessity of additional surgical resection after the diagnosis of unsuspected N1 or N2 lymph node metastasis is limited.
Methods We conducted a multicenter, real-world data study of patients with any clinical T and N0 non-small cell lung cancer (NSCLC) who underwent lobectomy or segmentectomy between 2012 and 2021 and who subsequently received a diagnosis of pathologic N1 or N2 lymph node metastasis. Patients were categorized into lobectomy and segmentectomy groups. We analyzed overall survival (OS), recurrence-free survival (RFS), cumulative recurrence rates, and recurrence patterns using both unadjusted and propensity score–adjusted cohorts.
Results A total of 736 patients were in the lobectomy group, and 70 were in the segmentectomy group. In the unadjusted cohort, segmentectomy-treated patients were older, had a lower preoperative percentage of vital capacity, had smaller tumors, and received less postoperative adjuvant chemotherapy. The 5-year OS was significantly worse in the segmentectomy group (P = .011), with no significant differences in 5-year RFS or cumulative recurrence rates. In the propensity score–adjusted cohort, there were no significant differences in OS, RFS, or recurrence rates; however, the segmentectomy group had a higher rate of local recurrence.
Conclusions In patients with unsuspected N1 or N2 NSCLC, analysis using a cohort adjusted for patient background with propensity scores revealed no differences in OS, RFS, or cumulative recurrence rates between segmentectomy and lobectomy. This finding suggests that additional resection of the remaining segments may not be necessary for these patients. However, the higher rate of local recurrence in the segmentectomy group warrants careful consideration. en-copyright= kn-copyright= en-aut-name=RyukoTsuyoshi en-aut-sei=Ryuko en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UenoTsuyoshi en-aut-sei=Ueno en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiwaraToshiya en-aut-sei=Fujiwara en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeMototsugu en-aut-sei=Watanabe en-aut-mei=Mototsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=InokawaHidetoshi en-aut-sei=Inokawa en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MisaoTakahiko en-aut-sei=Misao en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TorigoeHidejiro en-aut-sei=Torigoe en-aut-mei=Hidejiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WashioKazuhiro en-aut-sei=Washio en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TaoHiroyuki en-aut-sei=Tao en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OkutaniDaisuke en-aut-sei=Okutani en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HayamaMakio en-aut-sei=Hayama en-aut-mei=Makio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=UomotoMasashi en-aut-sei=Uomoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YamadaEiji en-aut-sei=Yamada en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OtaniShinji en-aut-sei=Otani en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KurosakiTakeshi en-aut-sei=Kurosaki en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YaginumaYuji en-aut-sei=Yaginuma en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=NimanEito en-aut-sei=Niman en-aut-mei=Eito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KawamataOsamu en-aut-sei=Kawamata en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=NishikawaHitoshi en-aut-sei=Nishikawa en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OtsukaTomoaki en-aut-sei=Otsuka en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YoshikawaTakeshi en-aut-sei=Yoshikawa en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=HayashiTatsuro en-aut-sei=Hayashi en-aut-mei=Tatsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=7 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=8 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=9 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=10 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=11 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=12 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=13 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=14 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=15 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=16 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=17 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=18 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=19 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=20 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=21 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=22 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=23 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=24 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=25 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=26 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=27 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250726 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relationship between maternal body composition changes and heavy for date infants in pregnant women with diabetes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims/Introduction: Maternal hyperglycemia is associated with heavy for date (HFD) infants. Considering the association between body composition and hyperglycemia, we investigated the changes in maternal body composition and their relationship with HFD infants in pregnant women with diabetes.
Materials and Methods: Body composition was measured during pregnancy using a bioelectrical impedance analysis system. This retrospective study included 151 pregnant women; 27 women had type 1 diabetes mellitus (DM), 21 had type 2 DM, 101 were diagnosed with gestational DM, and 2 had overt DM. The number of HFD infants was 40.
Results: In the non-type 1 DM group, change in fat mass (ΔFM) (P < 0.01) and pre-pregnancy BMI (P < 0.05) were risk factors for HFD. In the insulin group, ΔFM, pre-pregnancy BMI, and age (all P < 0.05) were risk factors for HFD. The area under the curve was 0.813 for the predictive model combined with ΔFM and pre-pregnancy BMI in the non-type 1 DM group and 0.818 for the model combined with ΔFM, pre-pregnancy BMI, and age in the insulin group.
Conclusions: The combination of body composition parameters and clinical data may predict HFD in pregnant women with diabetes. en-copyright= kn-copyright= en-aut-name=EtoEriko en-aut-sei=Eto en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatoMasakazu en-aut-sei=Kato en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KirinoSatoe en-aut-sei=Kirino en-aut-mei=Satoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuriyamaChiaki en-aut-sei=Kuriyama en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakataSyujiro en-aut-sei=Sakata en-aut-mei=Syujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakatoHikari en-aut-sei=Nakato en-aut-mei=Hikari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MishimaSakurako en-aut-sei=Mishima en-aut-mei=Sakurako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhiraAkiko en-aut-sei=Ohira en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil= kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, 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 Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Fat mass gain kn-keyword=Fat mass gain en-keyword=Heavy for date kn-keyword=Heavy for date en-keyword=Maternal body composition kn-keyword=Maternal body composition END start-ver=1.4 cd-journal=joma no-vol=150 cd-vols= no-issue=1 article-no= start-page=19 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250813 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biallelic variants in DNAJC7 cause familial amyotrophic lateral sclerosis with the TDP-43 pathology en-subtitle= kn-subtitle= en-abstract= kn-abstract=Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons. ALS pathology primarily involves the failure of protein quality control mechanisms, leading to the accumulation of misfolded proteins, particularly TAR DNA-binding protein 43 (TDP-43). TDP-43 aggregation is a central pathological feature of ALS. Maintaining protein homeostasis is critical and facilitated by heat shock proteins (HSPs), particularly the HSP40 family, which includes co-chaperones such as DNAJC7. Here, we report a family with three siblings affected by ALS who carry a homozygous c.518dupC frameshift variant in DNAJC7, a member of the HSP40 family. All three patients exhibited progressive muscle weakness, limb atrophy, bulbar palsy, and respiratory failure. Pathological examination revealed degeneration of both upper and lower motor neurons, with phosphorylated TDP-43-positive neuronal cytoplasmic inclusions in the frontal and temporal cortices. Immunoblot analysis were consistent with a type B pattern of phosphorylated TDP-43 in the precentral gyrus. Immunohistochemistry and RNA sequencing analyses demonstrated a substantial reduction in DNAJC7 expression at both the protein and RNA levels in affected brain regions. In a TDP-43 cell model, DNAJC7 knockdown impaired the disassembly of TDP-43 following arsenite-induced stress, whereas DNAJC7 overexpression suppressed the assembly and promoted the disassembly of arsenite-induced TDP-43 condensates. Furthermore, in a zebrafish ALS model, dnajc7 knockdown resulted in increased TDP-43 aggregation in motor neurons and reduced survival. To the best of our knowledge, this study provides the first evidence linking biallelic loss-of-function variants in DNAJC7 to familial ALS with TDP-43 pathology. en-copyright= kn-copyright= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokotaOsamu en-aut-sei=Yokota en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OusakaDaiki en-aut-sei=Ousaka en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SunHongming en-aut-sei=Sun en-aut-mei=Hongming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraguchiTakashi en-aut-sei=Haraguchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Ota-ElliottRicardo Satoshi en-aut-sei=Ota-Elliott en-aut-mei=Ricardo Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuokaChika en-aut-sei=Matsuoka en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawanoTomohito en-aut-sei=Kawano en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Nakashima-YasudaHanae en-aut-sei=Nakashima-Yasuda en-aut-mei=Hanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FukuiYusuke en-aut-sei=Fukui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakanoYumiko en-aut-sei=Nakano en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HasegawaMasato en-aut-sei=Hasegawa en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HosonoYasuyuki en-aut-sei=Hosono en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TeradaSeishi en-aut-sei=Terada en-aut-mei=Seishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurology, National Hospital Organisation Minami-Okayama Medical Centre kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Psychiatry, Zikei Hospital kn-affil= affil-num=10 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Brain and Neurosciences, Tokyo Metropolitan Institute of Medical Science kn-affil= affil-num=14 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Amyotrophic lateral sclerosis kn-keyword=Amyotrophic lateral sclerosis en-keyword=Heat shock protein kn-keyword=Heat shock protein en-keyword=DNAJC7 kn-keyword=DNAJC7 en-keyword=TDP-43 kn-keyword=TDP-43 en-keyword=Live-cell imaging kn-keyword=Live-cell imaging en-keyword=Zebrafish disease model kn-keyword=Zebrafish disease model END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=6 article-no= start-page=e00110-25 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250519 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mycobacterium tuberculosis bacillus induces pyroptosis in human lung fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=We previously reported that live, but not dead, virulent Mycobacterium tuberculosis (Mtb) H37Rv bacilli induce cell death in human lung fibroblast cell lines, MRC-5, MRC-9, and TIG-1. Here, using two distinct Mtb strains from two different lineages (HN878 lineage 2 and H37Rv lineage 4), we confirmed cell death at day 2 after infection with a device that measures cell growth/cytotoxicity in real time (Maestro-Z [AXION]). Mtb bacilli uptake by the fibroblast was confirmed with a transmission electron microscope on day 2. Expressions of inflammatory cytokines and interleukin (IL)−1β, IL-6, and IL-8 were observed when exposed to live, but not dead bacteria. The cell death of fibroblasts induced by both Mtb strains tested was prevented by caspase-1/4 and NLRP3 inflammasome inhibitors, but not by caspase-3 and caspase-9 inhibitors. Therefore, we classified the fibroblast cell death by Mtb infection as pyroptosis. To investigate the biological and pathological relevance of fibroblast cell death by Mtb infection, we performed dual RNA-Seq analysis on Mtb within fibroblasts and Mtb-infected fibroblasts at day 2. In Mtb bacilli tcrR, secE2, ahpD, and mazF8 genes were highly induced during infection. These genes play roles in survival in a hypoxic environment, production of a calcium-binding protein-inducing cytokine, and regulation of transcription in a toxin-antitoxin system. The gene expressions of IL-1β, IL-6, and IL-8, caspase-4, and NLRP3, but not of caspase-3 and caspase-9, were augmented in Mtb bacilli-infected fibroblasts. Taken together, our study suggests that Mtb bacilli attempt to survive in lung fibroblasts and that pyroptosis of the host fibroblasts activates the immune system against the infection. en-copyright= kn-copyright= en-aut-name=TakiiTakemasa en-aut-sei=Takii en-aut-mei=Takemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamadaHiroyuki en-aut-sei=Yamada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotozonoChihiro en-aut-sei=Motozono en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamasakiSho en-aut-sei=Yamasaki en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TorrellesJordi B. en-aut-sei=Torrelles en-aut-mei=Jordi B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TurnerJoanne en-aut-sei=Turner en-aut-mei=Joanne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimishimaAoi en-aut-sei=Kimishima en-aut-mei=Aoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AsamiYukihiro en-aut-sei=Asami en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OharaNaoya en-aut-sei=Ohara en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HidaShigeaki en-aut-sei=Hida en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HayashiHidetoshi en-aut-sei=Hayashi en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OnozakiKikuo en-aut-sei=Onozaki en-aut-mei=Kikuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=2 en-affil=Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=3 en-affil=Department of Molecular Immunology, Research Institute for Microbial Diseases, The University of Osaka kn-affil= affil-num=4 en-affil=Department of Molecular Immunology, Research Institute for Microbial Diseases, The University of Osaka kn-affil= affil-num=5 en-affil=Texas Biomedical Research Institute and International Center for the Advancement of Research & Education (I•CARE) kn-affil= affil-num=6 en-affil=Texas Biomedical Research Institute and International Center for the Advancement of Research & Education (I•CARE) kn-affil= affil-num=7 en-affil=Laboratory of Applied Microbial Chemistry, Ōmura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=8 en-affil=Laboratory of Applied Microbial Chemistry, Ōmura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=9 en-affil=Department of Oral Microbiology, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=11 en-affil=Department of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=12 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= en-keyword=Mycobacterium tuberculosis kn-keyword=Mycobacterium tuberculosis en-keyword=pyroptosis kn-keyword=pyroptosis en-keyword=caspase kn-keyword=caspase en-keyword=RNA-Seq kn-keyword=RNA-Seq en-keyword=cytokine kn-keyword=cytokine en-keyword=fibroblasts kn-keyword=fibroblasts END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=12 article-no= start-page=e202402802 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241001 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Chromosome-specific barcode system with centromeric repeat in cultivated soybean and wild progenitor en-subtitle= kn-subtitle= en-abstract= kn-abstract=Wild soybean Glycine soja is the progenitor of cultivated soybean Glycine max. Information on soybean functional centromeres is limited despite extensive genome analysis. These species are an ideal model for studying centromere dynamics for domestication and breeding. We performed a detailed chromatin immunoprecipitation analysis using centromere-specific histone H3 protein to delineate two distinct centromeric DNA sequences with unusual repeating units with monomer sizes of 90–92 bp (CentGm-1) and 413-bp (CentGm-4) shorter and longer than standard nucleosomes. These two unrelated DNA sequences with no sequence similarity are part of functional centromeres in both species. Our results provide a comparison of centromere properties between a cultivated and a wild species under the effect of the same kinetochore protein. Possible sequence homogenization specific to each chromosome could highlight the mechanism for evolutionary conservation of centromeric properties independent of domestication and breeding. Moreover, a unique barcode system to track each chromosome is developed using CentGm-4 units. Our results with a unifying centromere composition model using CentGm-1 and CentGm-4 superfamilies could have far-reaching implications for comparative and evolutionary genome research. en-copyright= kn-copyright= en-aut-name=TekAhmet L en-aut-sei=Tek en-aut-mei=Ahmet L kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagakiKiyotaka en-aut-sei=Nagaki en-aut-mei=Kiyotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Yıldız AkkamışHümeyra en-aut-sei=Yıldız Akkamış en-aut-mei=Hümeyra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaKeisuke en-aut-sei=Tanaka en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiHisato en-aut-sei=Kobayashi en-aut-mei=Hisato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Agricultural Genetic Engineering, Ayhan Şahenk Faculty of Agricultural Sciences and Technologies, Niğde Ömer Halisdemir University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Department of Agricultural Genetic Engineering, Ayhan Şahenk Faculty of Agricultural Sciences and Technologies, Niğde Ömer Halisdemir University kn-affil= affil-num=4 en-affil=NODAI Genome Research Center, Tokyo University of Agriculture kn-affil= affil-num=5 en-affil=NODAI Genome Research Center, Tokyo University of Agriculture kn-affil= END start-ver=1.4 cd-journal=joma no-vol=35 cd-vols= no-issue=4 article-no= start-page=715 end-page=721 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250213 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Telemedicine as an alternative to in-person care in the field of rheumatic diseases: A systematic scoping review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: The COVID-19 pandemic prompted the widespread adoption of telemedicine as an alternative to in-person care. This systematic scoping review evaluated the effectiveness, cost-efficiency, and challenges of telemedicine for patients with rheumatic diseases.
Methods: A comprehensive search of the MEDLINE database was conducted using specific terms related to rheumatoid or juvenile arthritis, and telemedicine. The literature search included studies published up to March, 2024. In this review, we only considered studies assessing telemedicine as an alternative to in-person care.
Results: The search, conducted on 15 March 2024, generated 258 references. Eight reports from three randomized controlled trials and three observational studies were included. Randomized controlled trials have shown that the outcomes of telemedicine intervention are comparable to those of in-person care in terms of disease activity, functional status, and quality of life, while enabling fewer outpatient visits and cost-effectiveness. However, the high dropout rates highlight the importance of patient preferences and comprehensive education. Observational studies revealed similar findings but were limited by a high confounding bias.
Conclusion: Telemedicine offers economic advantages and maintains clinical outcomes comparable to those of in-person care. Its success depends on structured patient education and alignment with patient preferences. Further research is required, particularly in the context of healthcare in Japan. en-copyright= kn-copyright= en-aut-name=SadaKen-ei en-aut-sei=Sada en-aut-mei=Ken-ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwataShigeru en-aut-sei=Iwata en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InoueYuzaburo en-aut-sei=Inoue en-aut-mei=Yuzaburo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaEiichi en-aut-sei=Tanaka en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishidaKeiichiro en-aut-sei=Nishida en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawahitoYutaka en-aut-sei=Kawahito en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AbeAsami en-aut-sei=Abe en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawakamiAtsushi en-aut-sei=Kawakami en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyamaeTakako en-aut-sei=Miyamae en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Clinical Epidemiology, Kochi Medical School kn-affil= affil-num=2 en-affil=Department of Rheumatology and Clinical Immunology, Wakayama Medical University kn-affil= affil-num=3 en-affil=Department of General Medical Science, Graduate School of Medicine, Chiba University kn-affil= affil-num=4 en-affil=Department of Rheumatology, Tokyo Women’s Medical University School of Medicine kn-affil= affil-num=5 en-affil=Locomotive Pain Center, Okayama University Hospital kn-affil= affil-num=6 en-affil=Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=7 en-affil=Department of Rheumatology, Niigata Rheumatic Center kn-affil= affil-num=8 en-affil=Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=9 en-affil=Department of Pediatric Rheumatology, Institute of Rheumatology, Tokyo Women’s Medical University kn-affil= en-keyword=Digital health kn-keyword=Digital health en-keyword=telemedicine kn-keyword=telemedicine en-keyword=remote care kn-keyword=remote care en-keyword=rheumatic disease kn-keyword=rheumatic disease en-keyword=scoping review kn-keyword=scoping review END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue= article-no= start-page=31 end-page=42 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Incidence, Management, and Prevention of Gynecomastia and Breast Pain in Patients with Prostate Cancer Undergoing Antiandrogen Therapy: A Systematic Review and Meta-analysis of Randomized Controlled Trials en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and objective: In patients with prostate cancer treated with antiandrogen monotherapy, gynecomastia and breast pain are relatively common. In the setting of androgen receptor pathway inhibitors (ARPIs), the incidence of these adverse events (AEs) remains unclear. In addition, the effect of prophylactic treatment on gynecomastia remains uncertain. We aimed to evaluate the incidence of gynecomastia and breast pain in prostate cancer patients treated with ARPIs compared with androgen deprivation therapy (ADT) and the effect of prophylactic treatment for these AEs due to antiandrogen therapy.
Methods: In June 2024, we queried four databases—PubMed, Scopus, Web of Science, and Embase—for randomized controlled trials (RCTs) investigating prostate cancer treatments involving antiandrogen therapy. The endpoints of interest were the incidence of these AEs due to ARPIs and the effect of prophylactic treatment for these.
Key findings and limitations: Eighteen RCTs, comprising 5036 patients, were included in the systematic review and meta-analysis. ARPIs included enzalutamide, darolutamide, and apalutamide. The results indicated that patients who received ARPI monotherapy had a significantly higher incidence of gynecomastia than those who received ADT monotherapy (risk ratio [RR]: 5.19, 95% confidence interval [CI]: 3.58–7.51, p < 0.001). There was no significant difference in the incidence of gynecomastia between ARPI plus ADT therapy and ADT monotherapy (RR: 1.27, 95% CI: 0.84–1.93, p = 0.2). Prophylactic tamoxifen or radiotherapy reduced significantly the incidence of gynecomastia and breast pain caused by bicalutamide monotherapy.
Conclusions and clinical implications: We found that ARPI monotherapy increases the incidence of these AEs significantly compared with ADT. In contrast, ARPI plus ADT therapy did not result in a higher incidence of AEs. The use of either tamoxifen or radiotherapy was effective in reducing the incidence of these AEs due to bicalutamide monotherapy. These prophylactic treatments could reduce the incidence of AEs due to ARPI monotherapy. However, further studies are needed to clarify their efficacy.
Patient summary: Although androgen deprivation therapy (ADT) improves overall survival in patients with prostate cancer, it is associated with several complications. Androgen receptor pathway inhibitor (ARPI) monotherapy has emerged as a promising strategy for improving oncological outcomes in these patients. However, ARPI monotherapy increases gynecomastia and breast pain in prostate cancer patients compared with ADT, while ARPI plus ADT did not result in a higher incidence of adverse events. en-copyright= kn-copyright= en-aut-name=TsuboiIchiro en-aut-sei=Tsuboi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SchulzRobert J. en-aut-sei=Schulz en-aut-mei=Robert J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LaukhtinaEkaterina en-aut-sei=Laukhtina en-aut-mei=Ekaterina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WadaKoichiro en-aut-sei=Wada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KarakiewiczPierre I. en-aut-sei=Karakiewicz en-aut-mei=Pierre I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShariatShahrokh F. en-aut-sei=Shariat en-aut-mei=Shahrokh F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=3 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=4 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=5 en-affil=Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= en-keyword=Antiandrogen therapy kn-keyword=Antiandrogen therapy en-keyword=Androgen deprivation therapy kn-keyword=Androgen deprivation therapy en-keyword=Androgen receptor pathway inhibitors kn-keyword=Androgen receptor pathway inhibitors en-keyword=Breast pain kn-keyword=Breast pain en-keyword=Gynecomastia kn-keyword=Gynecomastia END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=3 article-no= start-page=99 end-page=117 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240429 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Generation and characterization of cerebellar granule neurons specific knockout mice of Golli-MBP en-subtitle= kn-subtitle= en-abstract= kn-abstract=Golli–myelin basic proteins, encoded by the myelin basic protein gene, are widely expressed in neurons and oligodendrocytes in the central nervous system. Further, prior research has shown that Golli–myelin basic protein is necessary for myelination and neuronal maturation during central nervous system development. In this study, we established Golli–myelin basic protein-floxed mice to elucidate the cell-type-specific effects of Golli–myelin basic protein knockout through the generation of conditional knockout mice (Golli–myelin basic proteinsfl/fl; E3CreN), in which Golli–myelin basic proteins were specifically deleted in cerebellar granule neurons, where Golli–myelin basic proteins are expressed abundantly in wild-type mice. To investigate the role of Golli–myelin basic proteins in cerebellar granule neurons, we further performed histopathological analyses of these mice, with results indicating no morphological changes or degeneration of the major cellular components of the cerebellum. Furthermore, behavioral analysis showed that Golli–myelin basic proteinsfl/fl; E3CreN mice were healthy and did not display any abnormal behavior. These results suggest that the loss of Golli–myelin basic proteins in cerebellar granule neurons does not lead to cerebellar perturbations or behavioral abnormalities. This mouse model could therefore be employed to analyze the effect of Golli–myelin basic protein deletion in specific cell types of the central nervous system, such as other neuronal cells and oligodendrocytes, or in lymphocytes of the immune system. en-copyright= kn-copyright= en-aut-name=MiyazakiHaruko en-aut-sei=Miyazaki en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiokaSaki en-aut-sei=Nishioka en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamanakaTomoyuki en-aut-sei=Yamanaka en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbeManabu en-aut-sei=Abe en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImamuraYukio en-aut-sei=Imamura en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyasakaTomohiro en-aut-sei=Miyasaka en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KakudaNobuto en-aut-sei=Kakuda en-aut-mei=Nobuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OohashiToshitaka en-aut-sei=Oohashi en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShimogoriTomomi en-aut-sei=Shimogori en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamakawaKazuhiro en-aut-sei=Yamakawa en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IkawaMasahito en-aut-sei=Ikawa en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NukinaNobuyuki en-aut-sei=Nukina en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Molecular Biology and Biochemistry, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University kn-affil= affil-num=3 en-affil=Laboratory of Structural Neuropathology, Graduate School of Brain Science, Doshisha University kn-affil= affil-num=4 en-affil=Department of Animal Model Development, Brain Research Institute, Niigata University kn-affil= affil-num=5 en-affil=Laboratory of Structural Neuropathology, Graduate School of Brain Science, Doshisha University kn-affil= affil-num=6 en-affil=Faculty of Life and Medical Sciences, Doshisha University kn-affil= affil-num=7 en-affil=Faculty of Life and Medical Sciences, Doshisha University kn-affil= affil-num=8 en-affil=Department of Molecular Biology and Biochemistry, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Laboratory for Molecular Mechanisms of Brain Development, RIKEN Center for Brain Science kn-affil= affil-num=10 en-affil=Laboratory for Neurogenetics, RIKEN Center for Brain Science kn-affil= affil-num=11 en-affil=Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University kn-affil= affil-num=12 en-affil=Laboratory of Structural Neuropathology, Graduate School of Brain Science, Doshisha University kn-affil= en-keyword=Golli-MBP kn-keyword=Golli-MBP en-keyword=Cerebellar granule neuron kn-keyword=Cerebellar granule neuron en-keyword=CRISPR/Cas9 kn-keyword=CRISPR/Cas9 en-keyword=Conditional knockout kn-keyword=Conditional knockout END start-ver=1.4 cd-journal=joma no-vol=218 cd-vols= no-issue= article-no= start-page=104922 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Alteration of perineuronal nets and parvalbumin interneurons in prefrontal cortex and hippocampus, and correlation with blood corticosterone in activity-based anorexia model mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Anorexia nervosa (AN) is an eating disorder characterized by restricted energy intake, severely underweight status, and frequent hyperactivity. Previous research has shown structural and functional alterations in the medial prefrontal cortex (mPFC) and hippocampus of AN patients. To investigate the pathological mechanism of AN, we analyzed the expression and distribution of parvalbumin (PV) interneurons and perineuronal nets (PNNs), which are implicated in the pathology of neuropsychiatric disorders, in the mPFC and hippocampus dorsal (HPCd) and ventral (HPCv) using an activity-based anorexia (ABA) mouse model. We found that PNN expression and density increased in the mPFC, with minor alterations in the HPCd and HPCv of ABA mice. The expression and distribution of PV neurons were unchanged in the brains of ABA mice, except for a regional decrease in PV-expressing neuron density in the HPCd. Co-localization analysis showed an increased number of PNNs enwrapping PV-negative neurons in the mPFC of ABA mice. Furthermore, the upregulation of PNN expression in the mPFC was positively correlated with elevated blood corticosterone levels, a well-known stress indicator, in ABA mice. Our findings suggest that the increased expression and distribution of PNNs surrounding PV-negative neurons in the mPFC may indicate the pathological mechanisms of AN. en-copyright= kn-copyright= en-aut-name=NguyenHoang Duy en-aut-sei=Nguyen en-aut-mei=Hoang Duy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiHaruko en-aut-sei=Miyazaki en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaiHiroki en-aut-sei=Kawai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangZiyi en-aut-sei=Wang en-aut-mei=Ziyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakamotoShinji en-aut-sei=Sakamoto en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OohashiToshitaka en-aut-sei=Oohashi en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=anorexia nervosa kn-keyword=anorexia nervosa en-keyword=activity-based anorexia kn-keyword=activity-based anorexia en-keyword=perineuronal nets kn-keyword=perineuronal nets en-keyword=parvalbumin kn-keyword=parvalbumin en-keyword=corticosterone kn-keyword=corticosterone en-keyword=prefrontal cortex kn-keyword=prefrontal cortex en-keyword=hippocampus kn-keyword=hippocampus END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=158 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250719 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oncolytic virus-mediated p53 activation boosts the antitumor immunity of a p53-transduced dendritic cell vaccine en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dendritic cells (DCs) transduced with replication-deficient, wild-type human p53-expressing adenovirus Ad-p53 (Ad-p53 DCs) induce p53-targeting cytotoxic T lymphocytes (CTLs). However, the antitumor efficacy of Ad-p53 DCs is diminished by weak p53 immunogenicity in tumor cells and poor immune responses. We developed a p53-armed oncolytic adenovirus, OBP-702, to induce tumor-specific p53 expression and antitumor immune response, suggesting a role for OBP-702 in enhancing the antitumor efficacy of Ad-p53 DCs. The combined effect of Ad-p53 DCs and OBP-702 was investigated using murine colon cancer (CC) tumor models. Ad-p53 DCs were obtained by stimulating bone marrow-derived cells with granulocyte-macrophage colony-stimulating factor, interleukin-4, and Ad-p53. Subcutaneous tumor models of CT26 (p53 wild-type) and MC38 (p53 mutant-type) murine CC cell lines were used to evaluate the therapeutic potential of combination therapy in the terms of tumor growth, abscopal effect, antitumor immune response, and presentation of p53 peptides in tumor cells. Combination therapy with Ad-p53 DCs and OBP-702 significantly suppressed the growth of p53-intact CT26 tumors at treated and untreated sites by inducing tumor-infiltration of CD8+ CTLs and CD11c+ DCs. OBP-702-infected tumor cells presented human p53 epitopes in the context of major histocompatibility complex molecules, which were recognized by CTLs induced by Ad-p53 DCs. Combination therapy significantly suppressed the growth of p53-mutant MC38 tumors by activating the antitumor immune response. Our results suggest that OBP-702-mediated presentation of p53 epitopes on tumor cells enhances the antitumor efficacy of Ad-p53 DCs against murine CC tumors by attracting p53-targeting CTLs. en-copyright= kn-copyright= en-aut-name=YamadaMotohiko en-aut-sei=Yamada en-aut-mei=Motohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SuemoriKanto en-aut-sei=Suemori en-aut-mei=Kanto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkadaNaohiro en-aut-sei=Okada en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KajiwaraYoshinori en-aut-sei=Kajiwara en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShojiRyohei en-aut-sei=Shoji en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InoueHiroaki en-aut-sei=Inoue en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HashimotoNaoyuki en-aut-sei=Hashimoto en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Neutron Therapy Research Center, Okayama University Hospital kn-affil= affil-num=14 en-affil=Oncolys BioPharma, Inc kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=199 cd-vols= no-issue= article-no= start-page=108027 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real-world status of multimodal treatment of Stage IIIA-N2 non-small cell lung cancer in Japan: Results from the SOLUTION study, a non-interventional, multicenter cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: There is limited consensus on resectability criteria for Stage IIIA-N2 non-small cell lung cancer (NSCLC). We examined the patient characteristics, N2 status, treatment decisions, and clinical outcomes according to the treatment modality for Stage IIIA-N2 NSCLC in Japan.
Materials and methods: Patients with Stage IIIA-N2 NSCLC in Japan were consecutively registered in the SOLUTION study between 2013 and 2014. Patients were divided according to treatment (chemoradiotherapy [CRT], surgery + perioperative therapy [neoadjuvant and/or adjuvant therapy], surgery alone). Demographic characteristics, N2 status (number and morphological features), pathological information, and treatments were analyzed descriptively. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) were estimated using the Kaplan–Meier method.
Results: Of 227 patients registered, 133 underwent CRT, 56 underwent surgery + perioperative therapy, and 38 underwent surgery alone. The physicians reported the following reasons for unresectability for 116 of 133 CRT patients: large number of metastatic lymph nodes (70.7 %), extranodal infiltration (25.0 %), poor surgical tolerance (19.0 %), or other reasons (18.1 %). CRT was more frequently performed in patients whose lymph nodes had an infiltrative appearance (64.3 %) and was the predominant treatment in patients with multiple involved stations (discrete: 60.0 %; infiltrative: 80.4 %). Distant metastasis with/without local progression was found in 50.4 %, 50.0 %, and 36.8 % of patients in the CRT, surgery + perioperative therapy, and surgery alone groups, respectively. The respective 3-year OS and DFS/PFS rates (median values) were as follows: surgery + perioperative therapy—61.9 % (not reached) and 37.1 % (22.4 months; DFS); CRT group—42.2 % (31.9 months) and 26.8 % (12.0 months; PFS); surgery alone group—37.7 % (26.5 months) and 28.7 % (12.6 months; DFS).
Conclusion: This study has illuminated the real-world decision rules for choosing between surgical and non-surgical approaches in patients with Stage IIIA-N2 NSCLC. Our landmark data could support treatment decision making for using immune checkpoint inhibitors and targeted therapy for driver oncogenes in the perioperative therapy era. en-copyright= kn-copyright= en-aut-name=HorinouchiHidehito en-aut-sei=Horinouchi en-aut-mei=Hidehito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MurakamiHaruyasu en-aut-sei=Murakami en-aut-mei=Haruyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaHideyuki en-aut-sei=Harada en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SobueTomotaka en-aut-sei=Sobue en-aut-mei=Tomotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoTomohiro en-aut-sei=Kato en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AtagiShinji en-aut-sei=Atagi en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KozukiToshiyuki en-aut-sei=Kozuki en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TokitoTakaaki en-aut-sei=Tokito en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OizumiSatoshi en-aut-sei=Oizumi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SeikeMasahiro en-aut-sei=Seike en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MioTadashi en-aut-sei=Mio en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SoneTakashi en-aut-sei=Sone en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwaoChikako en-aut-sei=Iwao en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IwaneTakeshi en-aut-sei=Iwane en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KotoRyo en-aut-sei=Koto en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TsuboiMasahiro en-aut-sei=Tsuboi en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Oncology, Shizuoka Cancer Center kn-affil= affil-num=3 en-affil=Division of Radiation Therapy, Shizuoka Cancer Center kn-affil= affil-num=4 en-affil=Division of Environmental Medicine and Population Sciences, Graduate School of Medicine, Osaka University kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, National Hospital Organization Himeji Medical Cente kn-affil= affil-num=6 en-affil=Department of Thoracic Oncology, National Hospital Organization Kinki-Chuo Chest Medical Center kn-affil= affil-num=7 en-affil=Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=8 en-affil=Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center kn-affil= affil-num=10 en-affil=Department of Pulmonary Medicine and Oncology, Nippon Medical School Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, National Hospital Organization Kyoto Medical Center kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Kanazawa University Hospital kn-affil= affil-num=14 en-affil=Department of Medical, AstraZeneca K.K. kn-affil= affil-num=15 en-affil=Department of Medical, AstraZeneca K.K. kn-affil= affil-num=16 en-affil=Department of Medical, AstraZeneca K.K. kn-affil= affil-num=17 en-affil=Department of Thoracic Surgery, National Cancer Center Hospital East kn-affil= en-keyword=Non-small cell lung cancer kn-keyword=Non-small cell lung cancer en-keyword=Surgery kn-keyword=Surgery en-keyword=Adjuvant therapy kn-keyword=Adjuvant therapy en-keyword=Neoadjuvant therapy kn-keyword=Neoadjuvant therapy en-keyword=Chemoradiotherapy kn-keyword=Chemoradiotherapy en-keyword=Observational study kn-keyword=Observational study en-keyword=Retrospective study kn-keyword=Retrospective study END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Employment of artificial intelligence for an unbiased evaluation regarding the recovery of right ventricular function after mitral valve transcatheter edge-to-edge repair en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims Long-standing severe mitral regurgitation (MR) leads to left atrial (LA) enlargement, elevated pulmonary artery pressures, and ultimately right heart failure. While mitral valve transcatheter edge-to-edge repair (M-TEER) alleviates left-sided volume overload, its impact on right ventricular (RV) recovery is unclear. This study aims to use both conventional echocardiography and artificial intelligence to assess the recovery of RV function in patients undergoing M-TEER for severe MR.
Methods and results The change in RV function from baseline to 3-month follow-up was analysed in a dual-centre registry of patients undergoing M-TEER for severe MR. RV function was conventionally assessed by measuring the tricuspid annular plane systolic excursion (TAPSE). Additionally, RV function was evaluated using a deep learning model that predicts RV ejection fraction (RVEF) based on two-dimensional apical four-chamber view echocardiographic videos. Among the 851 patients who underwent M-TEER, the 1-year survival rate was 86.8%. M-TEER resulted in a significant reduction in both LA volume and estimated systolic pulmonary artery pressure (sPAP) levels (median LA volume: from 123 ml [interquartile range, IQR 92–169 ml] to 104 ml [IQR 78–142 ml], p < 0.001; median sPAP: from 46 mmHg [IQR 35–58 mmHg] to 41 mmHg [IQR 32–54 mmHg], p = 0.036). In contrast, TAPSE remained unchanged (median: from 17 mm [IQR 14–21 mm] to 18 mm [IQR 15–21 mm], p = 0.603). The deep learning model confirmed this finding, showing no significant change in predicted RVEF after M-TEER (median: from 43.1% [IQR 39.1–47.4%] to 43.2% [IQR 39.2–47.2%], p = 0.475).
Conclusions While M-TEER improves left-sided haemodynamics, it does not lead to significant RV function recovery, as confirmed by both conventional echocardiography and artificial intelligence. This finding underscores the importance of treating patients before irreversible right heart damage occurs. en-copyright= kn-copyright= en-aut-name=FortmeierVera en-aut-sei=Fortmeier en-aut-mei=Vera kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HesseAmelie en-aut-sei=Hesse en-aut-mei=Amelie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TrenkwalderTeresa en-aut-sei=Trenkwalder en-aut-mei=Teresa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TokodiMárton en-aut-sei=Tokodi en-aut-mei=Márton kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KovácsAttila en-aut-sei=Kovács en-aut-mei=Attila kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=RippenElena en-aut-sei=Rippen en-aut-mei=Elena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TervoorenJule en-aut-sei=Tervooren en-aut-mei=Jule kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FettMichelle en-aut-sei=Fett en-aut-mei=Michelle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HarmsenGerhard en-aut-sei=Harmsen en-aut-mei=Gerhard kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KühleinMoritz en-aut-sei=Kühlein en-aut-mei=Moritz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=CovarrubiasHéctor Alfonso Alvarez en-aut-sei=Covarrubias en-aut-mei=Héctor Alfonso Alvarez kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=von ScheidtMoritz en-aut-sei=von Scheidt en-aut-mei=Moritz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=RoskiFerdinand en-aut-sei=Roski en-aut-mei=Ferdinand kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=GerçekMuhammed en-aut-sei=Gerçek en-aut-mei=Muhammed kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SchusterTibor en-aut-sei=Schuster en-aut-mei=Tibor kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MayrN. Patrick en-aut-sei=Mayr en-aut-mei=N. Patrick kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=XhepaErion en-aut-sei=Xhepa en-aut-mei=Erion kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=LaugwitzKarl‐Ludwig en-aut-sei=Laugwitz en-aut-mei=Karl‐Ludwig kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=JonerMichael en-aut-sei=Joner en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=RudolphVolker en-aut-sei=Rudolph en-aut-mei=Volker kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=LachmannMark en-aut-sei=Lachmann en-aut-mei=Mark kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of General and Interventional Cardiology, Heart and Diabetes Center Northrhine-Westfalia, Ruhr University Bochum kn-affil= affil-num=2 en-affil=Department of Internal Medicine I, Klinikum rechts der Isar, TUM University Hospital, School of Medicine and Health, Technical University of Munich kn-affil= affil-num=3 en-affil=DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance kn-affil= affil-num=4 en-affil=Heart and Vascular Center, Semmelweis University kn-affil= affil-num=5 en-affil=Heart and Vascular Center, Semmelweis University kn-affil= affil-num=6 en-affil=Department of Internal Medicine I, Klinikum rechts der Isar, TUM University Hospital, School of Medicine and Health, Technical University of Munich kn-affil= affil-num=7 en-affil=Department of Internal Medicine I, Klinikum rechts der Isar, TUM University Hospital, School of Medicine and Health, Technical University of Munich kn-affil= affil-num=8 en-affil=Department of General and Interventional Cardiology, Heart and Diabetes Center Northrhine-Westfalia, Ruhr University Bochum kn-affil= affil-num=9 en-affil=Department of Physics, University of Johannesburg kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Okayama University kn-affil= affil-num=11 en-affil=Department of Cardiovascular Diseases, German Heart Center Munich, School of Medicine and Health, TUM University Hospital, Technical University of Munich kn-affil= affil-num=12 en-affil=Department of Cardiovascular Diseases, German Heart Center Munich, School of Medicine and Health, TUM University Hospital, Technical University of Munich kn-affil= affil-num=13 en-affil=DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance kn-affil= affil-num=14 en-affil=Department of Cardiovascular Diseases, German Heart Center Munich, School of Medicine and Health, TUM University Hospital, Technical University of Munich kn-affil= affil-num=15 en-affil=Department of General and Interventional Cardiology, Heart and Diabetes Center Northrhine-Westfalia, Ruhr University Bochum kn-affil= affil-num=16 en-affil=Department of Family Medicine, McGill University kn-affil= affil-num=17 en-affil=Institute of Anesthesiology, German Heart Center Munich, School of Medicine and Health, TUM University Hospital, Technical University of Munich kn-affil= affil-num=18 en-affil=DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance kn-affil= affil-num=19 en-affil=Department of Internal Medicine I, Klinikum rechts der Isar, TUM University Hospital, School of Medicine and Health, Technical University of Munich kn-affil= affil-num=20 en-affil=DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance kn-affil= affil-num=21 en-affil=Department of General and Interventional Cardiology, Heart and Diabetes Center Northrhine-Westfalia, Ruhr University Bochum kn-affil= affil-num=22 en-affil=Department of Internal Medicine I, Klinikum rechts der Isar, TUM University Hospital, School of Medicine and Health, Technical University of Munich kn-affil= en-keyword=Echocardiography kn-keyword=Echocardiography en-keyword=Mitral regurgitation kn-keyword=Mitral regurgitation en-keyword=Right ventricular dysfunction kn-keyword=Right ventricular dysfunction en-keyword=Deep learning kn-keyword=Deep learning en-keyword=Transcatheter edge-to-edge repair kn-keyword=Transcatheter edge-to-edge repair END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=2 article-no= start-page=101575 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=Simplified Outcome Prediction in Patients Undergoing Transcatheter Tricuspid Valve Intervention by Survival Tree-Based Modelling en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Patients with severe tricuspid regurgitation (TR) typically present with heterogeneity in the extent of cardiac dysfunction and extra-cardiac comorbidities, which play a decisive role for survival after transcatheter tricuspid valve intervention (TTVI).
Objectives This aim of this study was to create a survival tree-based model to determine the cardiac and extra-cardiac features associated with 2-year survival after TTVI.
Methods The study included 918 patients (derivation set, n = 631; validation set, n = 287) undergoing TTVI for severe TR. Supervised machine learning-derived survival tree-based modelling was applied to preprocedural clinical, laboratory, echocardiographic, and hemodynamic data.
Results Following univariate regression analysis to pre-select candidate variables for 2-year mortality prediction, a survival tree-based model was constructed using 4 key parameters. Three distinct cluster-related risk categories were identified, which differed significantly in survival after TTVI. Patients from the low-risk category (n = 261) were defined by mean pulmonary artery pressure ≤28 mm Hg and N-terminal pro–B-type natriuretic peptide ≤2,728 pg/mL, and they exhibited a 2-year survival rate of 85.5%. Patients from the high-risk category (n = 190) were defined by mean pulmonary artery pressure >28 mm Hg, right atrial area >32.5 cm2, and estimated glomerular filtration rate ≤51 mL/min, and they showed a significantly worse 2-year survival of only 52.6% (HR for 2-year mortality: 4.3, P < 0.001). Net re-classification improvement analysis demonstrated that this model was comparable to the TRI-Score and outperformed the EuroScore II in identifying high-risk patients. The prognostic value of risk phenotypes was confirmed by external validation.
Conclusions This simple survival tree-based model effectively stratifies patients with severe TR into distinct risk categories, demonstrating significant differences in 2-year survival after TTVI. en-copyright= kn-copyright= en-aut-name=FortmeierVera en-aut-sei=Fortmeier en-aut-mei=Vera kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LachmannMark en-aut-sei=Lachmann en-aut-mei=Mark kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=StolzLukas en-aut-sei=Stolz en-aut-mei=Lukas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=von SteinJennifer en-aut-sei=von Stein en-aut-mei=Jennifer kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RommelKarl-Philipp en-aut-sei=Rommel en-aut-mei=Karl-Philipp kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KassarMohammad en-aut-sei=Kassar en-aut-mei=Mohammad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GerçekMuhammed en-aut-sei=Gerçek en-aut-mei=Muhammed kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SchöberAnne R. en-aut-sei=Schöber en-aut-mei=Anne R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=StockerThomas J. en-aut-sei=Stocker en-aut-mei=Thomas J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OmranHazem en-aut-sei=Omran en-aut-mei=Hazem kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FettMichelle en-aut-sei=Fett en-aut-mei=Michelle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TervoorenJule en-aut-sei=Tervooren en-aut-mei=Jule kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KörberMaria I. en-aut-sei=Körber en-aut-mei=Maria I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HesseAmelie en-aut-sei=Hesse en-aut-mei=Amelie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HarmsenGerhard en-aut-sei=Harmsen en-aut-mei=Gerhard kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FriedrichsKai Peter en-aut-sei=Friedrichs en-aut-mei=Kai Peter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 ORCID= en-aut-name=RudolphTanja K. en-aut-sei=Rudolph en-aut-mei=Tanja K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=JonerMichael en-aut-sei=Joner en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=PfisterRoman en-aut-sei=Pfister en-aut-mei=Roman kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=BaldusStephan en-aut-sei=Baldus en-aut-mei=Stephan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=LaugwitzKarl-Ludwig en-aut-sei=Laugwitz en-aut-mei=Karl-Ludwig kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=WindeckerStephan en-aut-sei=Windecker en-aut-mei=Stephan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=PrazFabien en-aut-sei=Praz en-aut-mei=Fabien kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=LurzPhilipp en-aut-sei=Lurz en-aut-mei=Philipp kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=HausleiterJörg en-aut-sei=Hausleiter en-aut-mei=Jörg kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=RudolphVolker en-aut-sei=Rudolph en-aut-mei=Volker kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= affil-num=1 en-affil=Department of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum kn-affil= affil-num=2 en-affil=First Department of Medicine, Klinikum rechts der Isar, Technical University of Munich kn-affil= affil-num=3 en-affil=DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance kn-affil= affil-num=4 en-affil=Department of Cardiology, Heart Center, University of Cologne kn-affil= affil-num=5 en-affil=Department of Cardiology, Heart Center Leipzig, University of Leipzig kn-affil= affil-num=6 en-affil=Department of Cardiology, Inselspital Bern, Bern University Hospital kn-affil= affil-num=7 en-affil=Department of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum kn-affil= affil-num=8 en-affil=Department of Cardiology, Heart Center Leipzig, University of Leipzig kn-affil= affil-num=9 en-affil=DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance kn-affil= affil-num=10 en-affil=Department of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum kn-affil= affil-num=11 en-affil=Department of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum kn-affil= affil-num=12 en-affil=Department of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum kn-affil= affil-num=13 en-affil=Department of Cardiology, Heart Center, University of Cologne kn-affil= affil-num=14 en-affil=First Department of Medicine, Klinikum rechts der Isar, Technical University of Munich kn-affil= affil-num=15 en-affil=Department of Physics, University of Johannesburg kn-affil= affil-num=16 en-affil=Department of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum kn-affil= affil-num=17 en-affil=Department of Cardiovascular Medicine, Okayama University kn-affil= affil-num=18 en-affil=Department of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum kn-affil= affil-num=19 en-affil=DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance kn-affil= affil-num=20 en-affil=Department of Cardiology, Heart Center, University of Cologne kn-affil= affil-num=21 en-affil=Department of Cardiology, Heart Center, University of Cologne kn-affil= affil-num=22 en-affil=First Department of Medicine, Klinikum rechts der Isar, Technical University of Munich kn-affil= affil-num=23 en-affil=Department of Cardiology, Inselspital Bern, Bern University Hospital kn-affil= affil-num=24 en-affil=Department of Cardiology, Inselspital Bern, Bern University Hospital kn-affil= affil-num=25 en-affil=Department of Cardiology, Heart Center Leipzig, University of Leipzig kn-affil= affil-num=26 en-affil=DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance kn-affil= affil-num=27 en-affil=Department of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum kn-affil= en-keyword=machine learning kn-keyword=machine learning en-keyword=transcatheter tricuspid valve intervention kn-keyword=transcatheter tricuspid valve intervention en-keyword=tricuspid regurgitation kn-keyword=tricuspid regurgitation END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=6 article-no= start-page=466 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250617 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Artificial Intelligence Approach in Machine Learning-Based Modeling and Networking of the Coronavirus Pathogenesis Pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=The coronavirus pathogenesis pathway, which consists of severe acute respiratory syndrome (SARS) coronavirus infection and signaling pathways, including the interferon pathway, the transforming growth factor beta pathway, the mitogen-activated protein kinase pathway, the apoptosis pathway, and the inflammation pathway, is activated upon coronaviral infection. An artificial intelligence approach based on machine learning was utilized to develop models with images of the coronavirus pathogenesis pathway to predict the activation states. Data on coronaviral infection held in a database were analyzed with Ingenuity Pathway Analysis (IPA), a network pathway analysis tool. Data related to SARS coronavirus 2 (SARS-CoV-2) were extracted from more than 100,000 analyses and datasets in the IPA database. A total of 27 analyses, including nine analyses of SARS-CoV-2-infected human-induced pluripotent stem cells (iPSCs) and iPSC-derived cardiomyocytes and fibroblasts, and a total of 22 analyses of SARS-CoV-2-infected lung adenocarcinoma (LUAD), were identified as being related to “human” and “SARS coronavirus 2” in the database. The coronavirus pathogenesis pathway was activated in SARS-CoV-2-infected iPSC-derived cells and LUAD cells. A prediction model was developed in Python 3.11 using images of the coronavirus pathogenesis pathway under different conditions. The prediction model of activation states of the coronavirus pathogenesis pathway may aid in treatment identification. en-copyright= kn-copyright= en-aut-name=TanabeShihori en-aut-sei=Tanabe en-aut-mei=Shihori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=QuaderSabina en-aut-sei=Quader en-aut-mei=Sabina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OnoRyuichi en-aut-sei=Ono en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaHiroyoshi Y. en-aut-sei=Tanaka en-aut-mei=Hiroyoshi Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoAkihisa en-aut-sei=Yamamoto en-aut-mei=Akihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KojimaMotohiro en-aut-sei=Kojima en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=PerkinsEdward J. en-aut-sei=Perkins en-aut-mei=Edward J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CabralHoracio en-aut-sei=Cabral en-aut-mei=Horacio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences kn-affil= affil-num=2 en-affil=Innovation Centre of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion kn-affil= affil-num=3 en-affil=Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences kn-affil= affil-num=4 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Mechanical Systems Engineering, Graduate School of Systems Design Tokyo Metropolitan University kn-affil= affil-num=6 en-affil=Department of Surgical Pathology, Kyoto Prefecture University of Medicine kn-affil= affil-num=7 en-affil=US Army Engineer Research and Development Center kn-affil= affil-num=8 en-affil=Department of Bioengineering, Graduate School of Engineering, The University of Tokyo kn-affil= en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=coronavirus kn-keyword=coronavirus en-keyword=coronaviral infection kn-keyword=coronaviral infection en-keyword=machine learning kn-keyword=machine learning en-keyword=pathway analysis kn-keyword=pathway analysis en-keyword=predictionmodel kn-keyword=predictionmodel en-keyword=molecular network kn-keyword=molecular network en-keyword=molecular pathway image kn-keyword=molecular pathway image en-keyword=network analysis kn-keyword=network analysis END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=11 article-no= start-page=4984 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250522 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Induced Pluripotent Stem Cells in Cardiomyopathy: Advancing Disease Modeling, Therapeutic Development, and Regenerative Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cardiomyopathies are a heterogeneous group of heart muscle diseases that can lead to heart failure, arrhythmias, and sudden cardiac death. Traditional animal models and in vitro systems have limitations in replicating the complex pathology of human cardiomyopathies. Induced pluripotent stem cells (iPSCs) offer a transformative platform by enabling the generation of patient-specific cardiomyocytes, thus opening new avenues for disease modeling, drug discovery, and regenerative therapy. This process involves reprogramming somatic cells into iPSCs and subsequently differentiating them into functional cardiomyocytes, which can be characterized using techniques such as electrophysiology, contractility assays, and gene expression profiling. iPSC-derived cardiomyocyte (iPSC-CM) platforms are also being explored for drug screening and personalized medicine, including high-throughput testing for cardiotoxicity and the identification of patient-tailored therapies. While iPSC-CMs already serve as valuable models for understanding disease mechanisms and screening drugs, ongoing advances in maturation and bioengineering are bringing iPSC-based therapies closer to clinical application. Furthermore, the integration of multi-omics approaches and artificial intelligence (AI) is enhancing the predictive power of iPSC models. iPSC-based technologies are paving the way for a new era of personalized cardiology, with the potential to revolutionize the management of cardiomyopathies through patient-specific insights and regenerative strategies. en-copyright= kn-copyright= en-aut-name=VoQuan Duy en-aut-sei=Vo en-aut-mei=Quan Duy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=induced pluripotent stem cells kn-keyword=induced pluripotent stem cells en-keyword=cardiomyopathy kn-keyword=cardiomyopathy en-keyword=disease modeling kn-keyword=disease modeling en-keyword=drug screening kn-keyword=drug screening en-keyword=regenerative therapy kn-keyword=regenerative therapy END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=13 article-no= start-page=7238 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250627 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Protective Effects of the Ethyl Acetate Fraction of Distylium racemosum Against Metabolic Dysfunction-Associated Steatohepatitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Metabolic dysfunction-associated steatohepatitis (MASH), previously referred to as non-alcoholic steatohepatitis (NASH), which is a progressive non-alcoholic fatty liver disease, is accompanied by hepatic steatosis, inflammation, and fibrosis. Despite its increasing prevalence, available treatment options for MASH are limited. Here, we investigated the protective effects of the Distylium racemosum ethyl acetate fraction (DRE) using MASH models and explored its key physiologically active components. Palmitic acid (PA)-induced AML12 hepatocytes and high-fat methionine- and choline-deficient-fed C57BL/6 mice were used as MASH models. Lipid accumulation was evaluated via triglyceride measurement, oil red O staining, and histological analysis. Lipid accumulation, inflammation, and fibrosis-associated gene expression were evaluated via real-time polymerase chain reaction. The physiologically active components of DRE were identified via high-performance liquid chromatography. Lipid accumulation and triglyceride levels were significantly reduced in PA-treated AML12 cells following DRE treatment. Additionally, DRE inhibited the expression of genes involved in lipogenesis (FAS and SREBP1c), inflammation (CD68, IL-6, and MCP-1), and fibrosis (COL1A1, COL1A2, and TIMP1). DRE reduced the liver weight, liver-to-body weight ratio, and hepatic steatosis in MASH model mice. It increased carnitine palmitoyltransferase-1 levels and decreased CD36 and transforming growth factor-β levels in the MASH mouse liver. High-performance liquid chromatography revealed that the extract contained rutin flavonoid family members. Overall, DRE was involved in lipid metabolism, inflammation, and fibrosis regulation, exerting potent hepatoprotective effects partly attributed to rutin and serving as a potential preventive candidate for MASH. en-copyright= kn-copyright= en-aut-name=LeeYoung-Hyeon en-aut-sei=Lee en-aut-mei=Young-Hyeon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YeoMin-Ho en-aut-sei=Yeo en-aut-mei=Min-Ho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChangKyung-Soo en-aut-sei=Chang en-aut-mei=Kyung-Soo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoonWeon-Jong en-aut-sei=Yoon en-aut-mei=Weon-Jong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimHye-Sook en-aut-sei=Kim en-aut-mei=Hye-Sook kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KimJongwan en-aut-sei=Kim en-aut-mei=Jongwan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimHye-Ran en-aut-sei=Kim en-aut-mei=Hye-Ran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan kn-affil= affil-num=2 en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan kn-affil= affil-num=3 en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan kn-affil= affil-num=4 en-affil=Clean Bio Business Division, Biodiversity Research Institute (JBRI), Jeju Technopark (JTP) kn-affil= affil-num=5 en-affil=Department of International Infectious Diseases Control, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Anatomy, College of Medicine, Dongguk University kn-affil= affil-num=7 en-affil=Department of Biomedical Laboratory Science, Dong-Eui Institute of Technology kn-affil= en-keyword=metabolic dysfunction-associated steatohepatitis kn-keyword=metabolic dysfunction-associated steatohepatitis en-keyword=Distylium racemosum kn-keyword=Distylium racemosum en-keyword=ethyl acetate fraction kn-keyword=ethyl acetate fraction en-keyword=extract kn-keyword=extract END start-ver=1.4 cd-journal=joma no-vol=135 cd-vols= no-issue=13 article-no= start-page=e172988 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250513 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=LAG3 regulates antibody responses in a murine model of kidney transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Lymphocyte activation gene 3 (LAG3) is a coinhibitory receptor expressed by various immune cells. Although the immunomodulatory potential of LAG3 is being explored in cancer and autoimmunity, there is no information on its role after organ transplantation. Our study investigated the functions of LAG3 in a mouse model of renal allograft rejection. LAG3–/– recipients rapidly rejected MHC-mismatched renal allografts that were spontaneously accepted by WT recipients, with graft histology characteristic of antibody-mediated rejection. Depletion of recipient B cells but not CD8+ T cells significantly extended kidney allograft survival in LAG3–/– recipients. Treatment of WT recipients with an antagonistic LAG3 antibody enhanced anti-donor immune responses and induced kidney damage associated with chronic rejection. The studies of conditional LAG3–/– recipients and mixed bone marrow chimeras demonstrated that LAG3 expression on either T or B cells is sufficient to regulate anti-donor humoral immunity but not to induce acute allograft rejection. The numbers and proinflammatory functions of graft-infiltrating NK cells were markedly increased in LAG3–/– recipients, suggesting that LAG3 also regulates the effector stage of antibody-mediated rejection. These findings identified LAG3 as a regulator of immune responses to kidney allografts and a potential therapeutic target for antibody-mediated rejection prevention and treatment. en-copyright= kn-copyright= en-aut-name=NicosiaMichael en-aut-sei=Nicosia en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FanRan en-aut-sei=Fan en-aut-mei=Ran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LeeJuyeun en-aut-sei=Lee en-aut-mei=Juyeun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AllGabriella en-aut-sei=All en-aut-mei=Gabriella kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GorbachevaVictoria en-aut-sei=Gorbacheva en-aut-mei=Victoria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ValenzuelaJosé I. en-aut-sei=Valenzuela en-aut-mei=José I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoYosuke en-aut-sei=Yamamoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BeaversAshley en-aut-sei=Beavers en-aut-mei=Ashley kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=DvorinaNina en-aut-sei=Dvorina en-aut-mei=Nina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=BaldwinWilliam M. en-aut-sei=Baldwin en-aut-mei=William M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ChuluyanEduardo en-aut-sei=Chuluyan en-aut-mei=Eduardo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=GaudetteBrian T. en-aut-sei=Gaudette en-aut-mei=Brian T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FairchildRobert L. en-aut-sei=Fairchild en-aut-mei=Robert L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MinBooki en-aut-sei=Min en-aut-mei=Booki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ValujskikhAnna en-aut-sei=Valujskikh en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=2 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=3 en-affil=Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=4 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=5 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=6 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=7 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=8 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=9 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=10 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=11 en-affil=Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Facultad de Medicina kn-affil= affil-num=12 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=14 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=15 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=16 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=107 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250428 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of concomitant medications on the oncologic efficacy of systemic therapy in patients with advanced or metastatic urothelial carcinoma: a systematic review and meta-analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Immune checkpoint inhibitors (ICI) and chemotherapy, including antibody-drug conjugates, are widely used for the treatment of patients with advanced unresectable or metastatic urothelial carcinoma (UC). The majority of elderly patients receive concomitant medications to address various comorbidities. We aimed to evaluate the impact of concomitant medications on oncological outcomes in patients with advanced unresectable or metastatic UC treated with systemic therapy.
Material & methods: In August 2024, three datasets were queried for studies evaluating concomitant medications in patients with advanced unresectable or metastatic UC. The review protocol was registered in PROSPERO (CRD42024547335). The primary outcome was overall survival (OS). A fixed- or random-effects model was used for meta-analysis depending on the heterogeneity.
Results: We identified 16 eligible studies (3 prospective and 13 retrospective) comprising 4,816 patients. Most reported concomitant medications included proton pump inhibitors (PPIs), antibiotics, steroids, and opioids. The use of concomitant PPIs, antibiotics, steroids or opioids during ICI therapy was associated with worsened OS (PPIs: HR: 1.43, 95% CI: 1.31–1.57, p < 0.001; antibiotics: HR: 1.2, 95% CI: 1.04–1.38, p = 0.01; steroids: HR: 1.45, 95% CI: 1.25–1.67, p < 0.001; and opioids: HR: 1.74, 95% CI: 1.46–2.07, p < 0.001). Concomitant use of antibiotics during chemotherapy did not impact OS (HR: 1.01, 95% CI: 0.67–1.51).
Conclusions: When treating advanced unresectable or metastatic UC with ICI therapy, we need to pay attention to concomitant medications, such as PPIs and antibiotics to avoid reducing the efficacy of ICI therapy. The mechanism of action of these drugs on ICI efficacy requires further examination. en-copyright= kn-copyright= en-aut-name=TsuboiIchiro en-aut-sei=Tsuboi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PariziMehdi Kardoust en-aut-sei=Parizi en-aut-mei=Mehdi Kardoust kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiszczykMarcin en-aut-sei=Miszczyk en-aut-mei=Marcin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FazekasTamás en-aut-sei=Fazekas en-aut-mei=Tamás kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SchulzRobert J en-aut-sei=Schulz en-aut-mei=Robert J kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LaukhtinaEkaterina en-aut-sei=Laukhtina en-aut-mei=Ekaterina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=RajwaPawel en-aut-sei=Rajwa en-aut-mei=Pawel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WadaKoichiro en-aut-sei=Wada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ObernederKatharina en-aut-sei=Oberneder en-aut-mei=Katharina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ChlostaPiotr en-aut-sei=Chlosta en-aut-mei=Piotr kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KarakiewiczPierre I. en-aut-sei=Karakiewicz en-aut-mei=Pierre I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ShariatShahrokh F. en-aut-sei=Shariat en-aut-mei=Shahrokh F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=3 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=4 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=5 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=6 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=7 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=8 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=13 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=14 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=15 en-affil=Department of Urology, Medical College, Jagiellonian University kn-affil= affil-num=16 en-affil=Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre kn-affil= affil-num=17 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= en-keyword=Concomitant medications kn-keyword=Concomitant medications en-keyword=Proton pump inhibitors kn-keyword=Proton pump inhibitors en-keyword=Antibiotics kn-keyword=Antibiotics en-keyword=steroids kn-keyword=steroids en-keyword=Opioids kn-keyword=Opioids en-keyword=Histamine type-2 receptor antagonists kn-keyword=Histamine type-2 receptor antagonists en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors en-keyword=Urothelial carcinoma kn-keyword=Urothelial carcinoma END start-ver=1.4 cd-journal=joma no-vol=144-145 cd-vols= no-issue= article-no= start-page=109001 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Investigating the fate of Zirconium-89 labelled antibody in cynomolgus macaques en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Preclinical pharmacokinetic studies of therapeutic antibodies in non-human primates are desired because of the difficulty in extrapolating ADME data from animal models to humans. We evaluated the pharmacokinetics of 89Zr (Zirconium-89) -labelled anti-KLH human IgG and its metabolites to confirm their non-specific/physiological accumulation in healthy cynomolgus macaques. The anti-KLH antibody was used as a negative control, ensuring that the observed distribution reflected general IgG behavior rather than antigen-specific accumulation. This provides a valuable reference for comparing the biodistribution of targeted antibodies.
Methods: Selected IgG was conjugated to desferrioxamine (DFO), labelled with 89Zr, and injected into healthy cynomolgus macaques. PET/CT images at the whole-body level were acquired at different time points, and standard uptake values (SUV) in regions of interest, such as the heart, liver, spleen, kidneys, bone, and muscles, were calculated. The distribution of a shortened antibody variant, 89Zr-labelled Fab, as well as that of [89Zr]Zr-DFO and [89Zr]Zr-oxalate, the expected metabolites of 89Zr- labelled IgG, was also assessed.
Results: After 89Zr-labelled IgG injection, the SUV in the heart, vertebral body, and muscle decreased, in line with the 89Zr concentration decrease in the circulation, whereas radioactivity increased over time in the kidneys and liver. Autoradiography of the renal sections indicated that most of the 89Zr- labelled IgG radioactivity accumulated in the renal cortex. Relatively high accumulation in the kidneys was also observed in 89Zr- labelled Fab-injected macaques, and renal autoradiographs of these animals showed that the renal cortex was the preferred accumulation site. However, [89Zr]Zr-DFO was rapidly excreted into the urine, whereas [89Zr]Zr-oxalate was highly accumulated in the epiphysis of the long bones and vertebral body.
Conclusion: In the non-human primate cynomolgus macaque, 89Zr- labelled IgG accumulated in the kidneys and the liver. However, [89Zr]Zr-DFO and 89Zr did not accumulate in these organs. This preclinical pharmacokinetic study performed with human IgG in a non-human primate model using PET is of great significance as it sheds light on the basic fate and distribution of 89Zr- labelled IgG. en-copyright= kn-copyright= en-aut-name=SasakiTakanori en-aut-sei=Sasaki en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuraSadaaki en-aut-sei=Kimura en-aut-mei=Sadaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NodaAkihiro en-aut-sei=Noda en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MurakamiYoshihiro en-aut-sei=Murakami en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyoshiSosuke en-aut-sei=Miyoshi en-aut-mei=Sosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkehiMasaru en-aut-sei=Akehi en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OchiaiKazuhiko en-aut-sei=Ochiai en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiguchiTakahiro en-aut-sei=Higuchi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Astellas Pharma Inc. kn-affil= affil-num=3 en-affil=Astellas Pharma Inc. kn-affil= affil-num=4 en-affil=Astellas Pharma Inc. kn-affil= affil-num=5 en-affil=Astellas Pharma Inc. kn-affil= affil-num=6 en-affil=Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=School of Veterinary Nursing and Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=8 en-affil=Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=PET imaging kn-keyword=PET imaging en-keyword=Zirconium-89 kn-keyword=Zirconium-89 en-keyword=Therapeutic antibodies kn-keyword=Therapeutic antibodies en-keyword=Non-human primates kn-keyword=Non-human primates END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=1 article-no= start-page=1 end-page=11 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluating Pericoronary Adipose Tissue Attenuation to Predict Cardiovascular Events en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Pericoronary adipose tissue attenuation (PCATA) is a novel imaging biomarker of pericoronary inflammation associated with coronary artery disease. Several studies have reported the usefulness of PCATA among people of European ethnicity; however, data are lacking concerning those of Asian ethnicity.
Objectives: This multicenter study aimed to evaluate the effect of PCATA on prognosis in East Asian patients.
Methods: Between August 2011 and December 2016, 2,172 patients underwent clinically indicated coronary computed tomography angiography (CTA) at 4 hospitals in Japan. Among them, 1,270 patients were analyzed. PCATA was evaluated using coronary CTA to measure pericoronary adipose tissue density surrounding the 3 major coronary arteries. The outcomes were composite cardiovascular events, including cardiovascular death and acute coronary syndrome; 33 cardiovascular events observed during a median follow-up of 6.0 years (Q1-Q3: 3.6-8.2 years).
Results: Right coronary artery (RCA)-PCATA was significantly higher in patients with cardiovascular events than in those without (−63.7 ± 8.9 HU vs −67.4 ± 9.1 HU, respectively; P = 0.021). High RCA-PCATA was significantly associated with cardiovascular events in a model that included the Hisayama risk score and adverse coronary CTA findings (HR: 1.55; 95% CI: 1.07-2.24; P = 0.019).
Conclusions: High RCA-PCATA showed significant association with future cardiovascular events after adjusting conventional risk factors and adverse coronary CTA findings in East Asian patients who underwent clinically indicated coronary CTA. en-copyright= kn-copyright= en-aut-name=NishiharaTakahiro en-aut-sei=Nishihara en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OsawaKazuhiro en-aut-sei=Osawa en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukeSoichiro en-aut-sei=Fuke en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SeiyamaKousuke en-aut-sei=Seiyama en-aut-mei=Kousuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DoiMasayuki en-aut-sei=Doi en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakashimaMitsutaka en-aut-sei=Nakashima en-aut-mei=Mitsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MikiTakashi en-aut-sei=Miki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of General Internal Medicine 3, Kawasaki Medical School General Medicine Center kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=6 en-affil=Department of Cardiology, Kagawa Prefectural Central Hospital kn-affil= affil-num=7 en-affil=Department of Cardiology, Kagawa Prefectural Central Hospital kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=acute coronary syndrome(s) kn-keyword=acute coronary syndrome(s) en-keyword=coronary computed tomography angiography kn-keyword=coronary computed tomography angiography en-keyword=high-risk plaque kn-keyword=high-risk plaque en-keyword=obstructive stenosis kn-keyword=obstructive stenosis en-keyword=pericoronary adipose tissue attenuation kn-keyword=pericoronary adipose tissue attenuation END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=6 article-no= start-page=1711 end-page=1720 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dotinurad Treatment for Patients With Hyperuricemia Complicating CKD en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: The management of hyperuricemia is important to reduce cardiovascular risk and the progression of renal injury in chronic kidney disease (CKD). This study aimed to assess the efficacy and safety of dotinurad, a novel urate transporter-1 inhibitor, in patients with hyperuricemia and CKD.
Methods: In a nonrandomized, parallel interventional study, patients were grouped based on their estimated glomerular filtration rate (eGFR) at baseline. The starting dotinurad dose was 0.5 mg/d and titrated to a final dose of 2 mg/d to 4 mg/d. The primary end point was the noninferiority of the change in serum uric acid (UA) levels between the G1/G2 and G3/G4 groups at week 24. The main secondary end points were changes in eGFR and UA clearance-to-creatinine clearance ratio (CUA/CCr). Reported adverse events were also investigated.
Results: Ninety-eight patients continued the dose titration. The mean percentage reduction in serum UA level at week 24 were 47.2% and 42.8% for the G1/G2 and G3/G4 groups, respectively; the between-group difference was −4.3% (95% confidence interval [CI], −9.5% to 0.9%, noninferiority P = 0.0321), validating the noninferiority of treatment in the G3/G4 group to the G1/G2 group. eGFR tended to increase slightly through to week 24, suggesting that spontaneous eGFR decline was counteracted. Mean CUA/CCr generally increased over time from week 4 to week 24. No new safety issues of particular concern were identified; and there were no marked changes in urinary pH.
Conclusion: Dotinurad therapy may be well-tolerated in patients with hyperuricemia and may have efficacy comparable with existing standard treatment in patients with CKD stages G3/G4. Randomized controlled trials in larger patient groups are needed. en-copyright= kn-copyright= en-aut-name=TanabeKatsuyuki en-aut-sei=Tanabe en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NunoueTomokazu en-aut-sei=Nunoue en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItabashiNaoki en-aut-sei=Itabashi en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatayamaAkihiro en-aut-sei=Katayama en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraAkihiko en-aut-sei=Nakamura en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhbayashiHiroyuki en-aut-sei=Ohbayashi en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OnishiYasuhiro en-aut-sei=Onishi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeKyoko en-aut-sei=Watanabe en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaruyamaKeisuke en-aut-sei=Maruyama en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HosoyaTakeshi en-aut-sei=Hosoya en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OkadaShinichi en-aut-sei=Okada en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Nunoue Clinic kn-affil= affil-num=3 en-affil=Itabashi Diabetes and Dermatology Medical Clinic kn-affil= affil-num=4 en-affil=NHO Okayama Medical Center kn-affil= affil-num=5 en-affil=Osafune Clinic kn-affil= affil-num=6 en-affil=Tohno Chuo Clinic kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Japanese Red Cross Okayama Hospital kn-affil= affil-num=9 en-affil=Okayama Saiseikai Outpatient Center Hospital kn-affil= affil-num=10 en-affil=Hosoya Clinic kn-affil= affil-num=11 en-affil=Okada Medical Clinic kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=chronic kidney disease kn-keyword=chronic kidney disease en-keyword=dotinurad kn-keyword=dotinurad en-keyword=efficacy kn-keyword=efficacy en-keyword=hyperuricemia kn-keyword=hyperuricemia en-keyword=safety kn-keyword=safety en-keyword=serum uric acid kn-keyword=serum uric acid END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=10 article-no= start-page=2401783 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biocompatibility of Water-Dispersible Pristine Graphene and Graphene Oxide Using a Close-to-Human Animal Model: A Pilot Study on Swine en-subtitle= kn-subtitle= en-abstract= kn-abstract=Graphene-based materials (GBMs) are of considerable interest for biomedical applications, and the pilot study on the toxicological and immunological impact of pristine graphene (GR) and graphene oxide (GO) using swine as a close-to-human provides valuable insights. First, ex vivo experiments are conducted on swine blood cells, then GBMs are injected intraperitoneally (i.p.) into swine. Hematological and biochemical analyses at various intervals indicate that neither GO nor GR cause systemic inflammation, pro-coagulant responses, or renal or hepatic dysfunction. Importantly, no systemic toxicity is observed. Analysis of a panel of 84 immune-related genes shows minimal impact of GO and GR. The animals are sacrificed 21 days post-injection, and transient absorption imaging and Raman mapping show the presence of GO and GR in the mesentery only. Histological evaluation reveals no signs of alterations in other organs. Thus, clusters of both materials are detected in the mesentery, and GO aggregates are surrounded only by macrophages with the formation of granulomas. In contrast, modest local reactions are observed around the GR clusters. Overall, these results reveal that i.p. injection of GBMs resulted in a modest local tissue reaction without systemic toxicity. This study, performed in swine, provides essential guidance for future biomedical applications of graphene. en-copyright= kn-copyright= en-aut-name=NicolussiPaola en-aut-sei=Nicolussi en-aut-mei=Paola kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PiloGiovannantonio en-aut-sei=Pilo en-aut-mei=Giovannantonio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=CanceddaMaria Giovanna en-aut-sei=Cancedda en-aut-mei=Maria Giovanna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PengGuotao en-aut-sei=Peng en-aut-mei=Guotao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChauNgoc Do Quyen en-aut-sei=Chau en-aut-mei=Ngoc Do Quyen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=De la CadenaAlejandro en-aut-sei=De la Cadena en-aut-mei=Alejandro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=VannaRenzo en-aut-sei=Vanna en-aut-mei=Renzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SamadYarjan Abdul en-aut-sei=Samad en-aut-mei=Yarjan Abdul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AhmedTanweer en-aut-sei=Ahmed en-aut-mei=Tanweer kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MarcellinoJeremia en-aut-sei=Marcellino en-aut-mei=Jeremia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TeddeGiuseppe en-aut-sei=Tedde en-aut-mei=Giuseppe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GiroLinda en-aut-sei=Giro en-aut-mei=Linda kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YlmazerAcelya en-aut-sei=Ylmazer en-aut-mei=Acelya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=LoiFederica en-aut-sei=Loi en-aut-mei=Federica kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=CartaGavina en-aut-sei=Carta en-aut-mei=Gavina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SecchiLoredana en-aut-sei=Secchi en-aut-mei=Loredana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=Dei GiudiciSilvia en-aut-sei=Dei Giudici en-aut-mei=Silvia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MacciocuSimona en-aut-sei=Macciocu en-aut-mei=Simona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=PolliDario en-aut-sei=Polli en-aut-mei=Dario kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=LigiosCiriaco en-aut-sei=Ligios en-aut-mei=Ciriaco kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=CerulloGiulio en-aut-sei=Cerullo en-aut-mei=Giulio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FerrariAndrea en-aut-sei=Ferrari en-aut-mei=Andrea kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=BiancoAlberto en-aut-sei=Bianco en-aut-mei=Alberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=FadeelBengt en-aut-sei=Fadeel en-aut-mei=Bengt kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=FranzoniGiulia en-aut-sei=Franzoni en-aut-mei=Giulia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=DeloguLucia Gemma en-aut-sei=Delogu en-aut-mei=Lucia Gemma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= affil-num=1 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=2 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=3 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=4 en-affil=Institute of Environmental Medicine, Karolinska Institutet kn-affil= affil-num=5 en-affil=CNRS, Immunology, Immunopathology and Therapeutic Chemistry kn-affil= affil-num=6 en-affil=Dipartimento di Fisica, Politecnico di Milano kn-affil= affil-num=7 en-affil=Istituto di Fotonica e Nanotecnologie – CNR kn-affil= affil-num=8 en-affil=Cambridge Graphene Centre, University of Cambridge kn-affil= affil-num=9 en-affil=Cambridge Graphene Centre, University of Cambridge kn-affil= affil-num=10 en-affil=Cambridge Graphene Centre, University of Cambridge kn-affil= affil-num=11 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=12 en-affil=ImmuneNano Laboratory, Department of Biomedical Sciences kn-affil= affil-num=13 en-affil=Department of Biomedical Engineering, Ankara University kn-affil= affil-num=14 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=15 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=16 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=17 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=18 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=19 en-affil=Dipartimento di Fisica, Politecnico di Milano kn-affil= affil-num=20 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=21 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=22 en-affil=Dipartimento di Fisica, Politecnico di Milano kn-affil= affil-num=23 en-affil=Cambridge Graphene Centre, University of Cambridge kn-affil= affil-num=24 en-affil=CNRS, Immunology, Immunopathology and Therapeutic Chemistry kn-affil= affil-num=25 en-affil=Institute of Environmental Medicine, Karolinska Institutet kn-affil= affil-num=26 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=27 en-affil=ImmuneNano Laboratory, Department of Biomedical Sciences kn-affil= en-keyword=2D materials kn-keyword=2D materials en-keyword=biocompatibility kn-keyword=biocompatibility en-keyword=immune system kn-keyword=immune system en-keyword=porcine model kn-keyword=porcine model en-keyword=toxicity kn-keyword=toxicity END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=11 article-no= start-page=uhae248 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240904 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A low-cost dpMIG-seq method for elucidating complex inheritance in polysomic crops: a case study in tetraploid blueberry en-subtitle= kn-subtitle= en-abstract= kn-abstract=Next-generation sequencing (NGS) library construction often requires high-quality DNA extraction, precise adjustment of DNA concentration, and restriction enzyme digestion to reduce genome complexity, which results in increased time and cost in sample preparation and processing. To address these challenges, a PCR-based method for rapid NGS library preparation, named dpMIG-seq, has been developed and proven effective for high-throughput genotyping. However, the application of dpMIG-seq has been limited to diploid and polyploid species with disomic inheritance. In this study, we obtained genome-wide single nucleotide polymorphism (SNP) markers for tetraploid blueberry to evaluate genotyping and downstream analysis outcomes. Comparison of genotyping qualities inferred across samples with different DNA concentrations and multiple bioinformatics approaches revealed high accuracy and reproducibility of dpMIG-seq-based genotyping, with Pearson's correlation coefficients between replicates in the range of 0.91 to 0.98. Furthermore, we demonstrated that dpMIG-seq enables accurate genotyping of samples with low DNA concentrations. Subsequently, we applied dpMIG-seq to a tetraploid F1 population to examine the inheritance probability of parental alleles. Pairing configuration analysis supported the random meiotic pairing of homologous chromosomes on a genome-wide level. On the other hand, preferential pairing was observed on chr-11, suggesting that there may be an exception to the random pairing. Genotypic data suggested quadrivalent formation within the population, although the frequency of quadrivalent formation varied by chromosome and cultivar. Collectively, the results confirmed applicability of dpMIG-seq for allele dosage genotyping and are expected to catalyze the adoption of this cost-effective and rapid genotyping technology in polyploid studies. en-copyright= kn-copyright= en-aut-name=NagasakaKyoka en-aut-sei=Nagasaka en-aut-mei=Kyoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraKazusa en-aut-sei=Nishimura en-aut-mei=Kazusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotokiKo en-aut-sei=Motoki en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamagataKeigo en-aut-sei=Yamagata en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiyamaSoichiro en-aut-sei=Nishiyama en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamaneHisayo en-aut-sei=Yamane en-aut-mei=Hisayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TaoRyutaro en-aut-sei=Tao en-aut-mei=Ryutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakanoRyohei en-aut-sei=Nakano en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakazakiTetsuya en-aut-sei=Nakazaki en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=5 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=6 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=7 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=8 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=9 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=94 cd-vols= no-issue=1 article-no= start-page=64 end-page=72 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=Development of an AI-based Image Analysis System to Calculate the Visit Duration of a Green Blow Fly on a Strawberry Flower en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pollinator insects are required to pollinate flowers in the production of some fruits and vegetables, and strawberries fall into this category. However, the function of pollinators has not been clarified by quantitative metrics such as the duration of pollinator visits needed by flowers. Due to the long activity time of pollinators (approximately 10-h), it is not easy to observe the visitation characteristics manually. Therefore, we developed software for evaluating pollinator performance using two types of artificial intelligence (AI), YOLOv4, which is an object detection AI, and VGG16, which is an image classifier AI. In this study, we used Phaenicia sericata Meigen (green blow fly) as the strawberry pollinator. The software program can automatically estimate the visit duration of a fly on a flower from video clips. First, the position of the flower is identified using YOLO, and the identified location is cropped. Next, the cropped image is classified by VGG16 to determine if the fly is on the flower. Finally, the results are saved in CSV and HTML format. The program processed 10 h of video (collected from 07:00 h to 17:00 h) taken under actual growing conditions to estimate the visit durations of flies on flowers. The recognition accuracy was approximately 97%, with an average difference of 550 s. The software was run on a small computer board (the Jetson Nano), indicating that it can easily be used without a complicated AI configuration. This means that the software can be used immediately by distributing pre-configured disk images. When the software was run on the Jetson Nano, it took approximately 11 min to estimate one day of 2-h video. It is therefore clear that the visit duration of a fly on a flower can be estimated much faster than by manually checking videos. Furthermore, this system can estimate the visit durations of pollinators to other flowers by changing the YOLO and VGG16 model files. en-copyright= kn-copyright= en-aut-name=TaniguchiHiroki en-aut-sei=Taniguchi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsukudaYuki en-aut-sei=Tsukuda en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotokiKo en-aut-sei=Motoki en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=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=YoshidaYuichi en-aut-sei=Yoshida en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=School of Agriculture 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=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=deep learning kn-keyword=deep learning en-keyword=fly kn-keyword=fly en-keyword=microcomputer kn-keyword=microcomputer en-keyword=VGG16 kn-keyword=VGG16 en-keyword=YOLO kn-keyword=YOLO END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=213 end-page=231 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250314 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=RKPM: Restricted Kernel Page Mechanism to Mitigate Privilege Escalation Attacks en-subtitle= kn-subtitle= en-abstract= kn-abstract=Kernel memory corruption attacks against operating systems exploit kernel vulnerabilities to overwrite kernel data. Kernel address space layout randomization makes it difficult to identify kernel data by randomizing their virtual address space. Control flow integrity (CFI) prevents unauthorized kernel code execution by verifying kernel function calls. However, these countermeasures do not prohibit writing to kernel data. If the virtual address of privileged information is specified and CFI is circumvented, the privileged information can be modified by a kernel memory corruption attack. In this paper, we propose a restricted kernel page mechanism (RKPM) to mitigate kernel memory corruption attacks by introducing restricted kernel pages to protect the kernel data specified in the kernel. The RKPM focuses on the fact that kernel memory corruption attacks attempt to read the virtual addresses around the privileged information. The RKPM adopts page table mapping handling and a memory protection key to control the read and write restrictions of the restricted kernel pages. This allows us to mitigate kernel memory corruption attacks by capturing reads to the restricted kernel page before the privileged information is overwritten. As an evaluation of the RKPM, we confirmed that it can mitigate privilege escalation attacks on the latest Linux kernel. We also measured that there was a certain overhead in the kernel performance. This study enhances kernel security by mitigating privilege escalation attacks through the use of software or hardware based restricted kernel pages. en-copyright= kn-copyright= en-aut-name=KuzunoHiroki en-aut-sei=Kuzuno en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamauchiToshihiro en-aut-sei=Yamauchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Graduate School of Engineering, Kobe University kn-affil= affil-num=2 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=66 end-page=73 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=kdMonitor: Kernel Data Monitor for Detecting Kernel Memory Corruption en-subtitle= kn-subtitle= en-abstract= kn-abstract=Privilege escalation attacks through memory corruption via kernel vulnerabilities pose significant threats to operating systems. Although the extended Berkley Packet Filter has been employed to trace kernel code execution by inserting interrupts before and after kernel code invocations, it does not track operations before and after kernel data writes, thus hindering effective kernel data monitoring. In this study, we introduce a kernel data monitor (kdMonitor), which is a novel security mechanism designed to detect unauthorized alterations in the monitored kernel data of a dedicated kernel page. The kdMonitor incorporates two distinct methods. The first is periodic monitoring which regularly outputs the monitored kernel data of the dedicated kernel pages. The second is dynamic monitoring, which restricts write access to a dedicated kernel page, supplements any write operations with page faults, and outputs the monitored kernel data of dedicated kernel pages. kdMonitor enables real-time tracking of specified kernel data of the dedicated kernel page residing in the kernel's virtual memory space from the separated machine. Using kdMonitor, we demonstrated its capability to pinpoint tampering with user process privileged information stemming from privilege escalation attacks on the kernel. Through an empirical evaluation, we validated the effectiveness of kdMonitor in detecting privilege escalation attacks by user processes on Linux. Performance assessments revealed that kdMonitor achieved an attack detection time of 0.83 seconds with an overhead of 0.726 %. en-copyright= kn-copyright= en-aut-name=KuzunoHiroki en-aut-sei=Kuzuno en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamauchiToshihiro en-aut-sei=Yamauchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Graduate School of Engineering, Kobe University kn-affil= affil-num=2 en-affil=Okayama University,Faculty of Environmental, Life, Natural Science and Technology kn-affil= en-keyword=Vulnerability countermeasure kn-keyword=Vulnerability countermeasure en-keyword=Operating system security kn-keyword=Operating system security en-keyword=System security kn-keyword=System security END start-ver=1.4 cd-journal=joma no-vol=57 cd-vols= no-issue=1 article-no= start-page=51 end-page=62 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250724 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Anticompetitive Exclusive Contracts with Complementary Inputs: A Case of Horizontally Differentiated Products kn-title=補完財供給企業存在時の反競争的な排他条件付取引契約―水平的差別化財のケース― en-subtitle= kn-subtitle= en-abstract= kn-abstract=　This study constructs a model of anticompetitive exclusive dealing in the presence of complementary inputs. Kitamura, Matsushima, and Sato （2018） analyze the situation where a downstream firm transforms multiple complementary inputs into final products. When complementary input suppliers have market power, the inefficient incumbent supplier can deter socially efficient entry by using exclusive contracts. This study applies the analysis from Kitamura, Matsushima, and Sato （2018） to examine a situation where the potential entrant produces horizontally differentiated products and demonstrates the feasibility of anticompetitive exclusive dealing. en-copyright= kn-copyright= en-aut-name=SatoMisato en-aut-sei=Sato en-aut-mei=Misato kn-aut-name=佐藤美里 kn-aut-sei=佐藤 kn-aut-mei=美里 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学学術研究院社会文化科学学域（経済） END start-ver=1.4 cd-journal=joma no-vol=57 cd-vols= no-issue=1 article-no= start-page=35 end-page=50 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250724 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A New Approach to Economic Ripple Effects in Regional Input-Output Tables kn-title=地域産業連関表における経済波及効果のNew Approach en-subtitle= kn-subtitle= en-abstract=　This paper first addresses the concept of economic ripple effects, highlighting that simulation results based on input-output tables often lead to overestimations. The primary reason for this overestimation lies in a misunderstanding of the underlying assumptions that generate ripple effects. Specifically, household consumption within a given region merely represents a transfer of money rather than a genuine economic impact. In principle, ripple effects should be understood as additional consumption resulting from increased income. In the absence of income growth, such effects largely represent consumption substitution or intertemporal shifts in spending. Furthermore, what is commonly referred to as “economic impact” is typically calculated as the cumulative total of sales revenue, which aggregates all monetary transactions indiscriminately. This approach differs from the concept of value-added effects, or income effects, which cannot exceed the initial inflow of money from outside the region. One of the factors contributing to these misinterpretations is the insufficient education on input-output analysis at universities. Additionally, computational tools provided by think tanks and public institutions for estimating ripple effects also present methodological issues. To address these challenges, this paper further refines a model previously proposed by the author that visualizes the ripple effect process. The study demonstrates, using real-world examples, the process of constructing ex-post input-output tables following exogenous impacts such as events. In particular, the paper introduces a “partially non-competitive import type” input structure as an alternative to the conventional competitive import-type input-output tables, which tend to overestimate the effects of changes in self-sufficiency rates. This new approach offers a more accurate framework for analyzing economic impacts. kn-abstract=　本稿では，まず経済波及効果の考え方について，産業連関表を用いたシミュレーションの結果が，しばしば過大評価になっていることを述べる。その理由として，経済波及効果をもたらす前提条件の考え方にしばしば誤解があることを指摘する。域内の居住者の消費はマネーの移転であり，真の経済効果ではない。波及効果とは，本来，所得が増えた結果の追加消費であって，所得が増えない状況では，代替消費や消費の先取りに過ぎないのである。また，一般にいう経済効果とは，売上高の積み上げであって同じマネーが何でも加算されているものであり，付加価値効果すなわち所得効果とは異なる。付加価値効果は，当初の域外から入ってきたマネー以上にはならない。こういった解釈の誤謬をもたらしているのは，大学での産業連関分析の教育が十分でないことも原因の1つであるが，シンクタンクや公的機関などで提供されている波及効果の計算ツールにも問題がある。そこで本稿では，これまで筆者が提唱してきた波及効果プロセスを見える化するモデルを更に精緻化し，イベントなど外生的インパクトが発生した後の事後的な産業連関表を構築する流れに関して実例を用いて説明を行う。特に自給率の変化の効果については，これまでの競争移入型連関表では効果が過大傾向になる問題点を解消するべく，「部分非競争移入型」の投入構造を提案し，新たな分析方法を提案する。 en-copyright= kn-copyright= en-aut-name=NakamuraRyohei en-aut-sei=Nakamura en-aut-mei=Ryohei kn-aut-name=中村良平 kn-aut-sei=中村 kn-aut-mei=良平 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=65 cd-vols= no-issue=7 article-no= start-page=319 end-page=325 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250715 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nationwide Survey of Middle Meningeal Artery Embolization for Chronic Subdural Hematoma in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Middle meningeal artery embolization has increasingly been used to treat chronic subdural hematoma. However, the current state of its application and outcomes in Japan remains unclear. We conducted a multicenter observational study involving facilities affiliated with the Japanese Society for Neuroendovascular Therapy to assess current practices and clarify the usefulness and safety of middle meningeal artery embolization for chronic subdural hematoma. A total of 466 patients from 40 facilities were included. The mean age of the patients was 78.0 ± 10.5 years, and bleeding risks, including antithrombotic therapy or bleeding predisposition, were present in 36.1% of patients. The most common timing for middle meningeal artery embolization was after the second burr hole surgery, accounting for 34.8% of cases. N-butyl-2-cyanoacrylate was used as the embolic material in 67% of cases. The complication rate was 5.2%, with complication-related morbidity at 0.9%. Hematomas were stable in 91.5% of cases at 30 days post-middle meningeal artery embolization. The symptomatic recurrence rate was 8.9%. Cases that underwent middle meningeal artery embolization after the second or subsequent burr hole surgeries were significantly associated with symptomatic recurrence. This study is the first nationwide survey investigating the real-world clinical practice of middle meningeal artery embolization for chronic subdural hematoma in Japan. While it included many elderly patients, recurrent cases, and those with bleeding risks, the safety and usefulness of middle meningeal artery embolization were deemed acceptable. However, symptomatic recurrence was common even in cases with middle meningeal artery embolization when performed after the second or subsequent burr hole surgeries. A further prospective study will be warranted to clarify treatment indications, optimal timing, and treatment techniques of middle meningeal artery embolization. en-copyright= kn-copyright= en-aut-name=MURAISatoshi en-aut-sei=MURAI en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EBISUDANIYuki en-aut-sei=EBISUDANI en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HARUMAJun en-aut-sei=HARUMA en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HIRAMATSUMasafumi en-aut-sei=HIRAMATSU en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HISHIKAWATomohito en-aut-sei=HISHIKAWA en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SATOWTetsu en-aut-sei=SATOW en-aut-mei=Tetsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SUGIUKenji en-aut-sei=SUGIU en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Neurosurgery, Kawasaki Medical School kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurosurgery, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Neurosurgery/Stroke Center, Kindai University Hospital kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=chronic subdural hematoma kn-keyword=chronic subdural hematoma en-keyword=endovascular therapy kn-keyword=endovascular therapy en-keyword=middle meningeal artery kn-keyword=middle meningeal artery END start-ver=1.4 cd-journal=joma no-vol=186 cd-vols= no-issue= article-no= start-page=118030 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=(+)-Terrein exerts anti-obesity and anti-diabetic effects by regulating the differentiation and thermogenesis of brown adipocytes in mice fed a high-fat diet en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: (+)-Terrein, a low-molecular-weight secondary metabolite from Aspergillus terreus, inhibits adipocyte differentiation in vitro. However, the precise mechanisms underlying the effects of (+)-terrein on adipocytes remain unclear. We hypothesized that (+)-terrein modulates adipogenesis and glucose homeostasis in obesity and diabetes via anti-inflammatory action and regulation of adipocyte differentiation. Hence, in this study, we aimed to investigate the in vivo anti-diabetic and anti-obesity effects of (+)-terrein.
Methods: Male C57BL/6 J mice were fed normal chow or high-fat (HF) diet and administered (+)-terrein (180 mg/kg) via intraperitoneal injection. Glucose and insulin tolerance tests, serum biochemical assays, and histological analyses were also performed. Rat brown preadipocytes, mouse brown preadipocytes (T37i cells), and inguinal white adipose tissue (ingWAT) preadipocytes were exposed to (+)-terrein during in vitro adipocyte differentiation. Molecular markers associated with thermogenesis and differentiation were quantified using real-time polymerase chain reaction and western blotting.
Results: (+)-Terrein-treated mice exhibited improved insulin sensitivity and reduced serum lipid and glucose levels, irrespective of the diet. Furthermore, (+)-terrein suppressed body weight gain and mitigated fat accumulation by activating brown adipose tissue in HF-fed mice. (+)-Terrein facilitated the in vitro differentiation of rat brown preadipocytes, T37i cells, and ingWAT preadipocytes by upregulating peroxisome proliferator-activated receptor-γ (PPARγ). This effect was synergistic with that of a PPARγ agonist.
Conclusion: This study demonstrated that (+)-terrein effectively induces PPARγ expression and brown adipocyte differentiation, leading to reduced weight gain and improved glucose and lipid profiles in HF-fed mice. Thus, (+)-terrein is a potent novel agent with potential anti-obesity and anti-diabetic properties. en-copyright= kn-copyright= en-aut-name=Aoki-SaitoHaruka en-aut-sei=Aoki-Saito en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MandaiHiroki en-aut-sei=Mandai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakakuraTakashi en-aut-sei=Nakakura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasakiTsutomu en-aut-sei=Sasaki en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KitamuraTadahiro en-aut-sei=Kitamura en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HisadaTakeshi en-aut-sei=Hisada en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkadaShuichi en-aut-sei=Okada en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugaSeiji en-aut-sei=Suga en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaMasanobu en-aut-sei=Yamada en-aut-mei=Masanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SaitoTsugumichi en-aut-sei=Saito en-aut-mei=Tsugumichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Allergy and Respiratory Medicine, Gunma University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science kn-affil= affil-num=3 en-affil=Department of Anatomy, Teikyo University School of Medicine kn-affil= affil-num=4 en-affil=Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University kn-affil= affil-num=5 en-affil=Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University kn-affil= affil-num=6 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Gunma University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=Department of Diabetes, Soleiyu Asahi Clinic kn-affil= affil-num=9 en-affil=Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University kn-affil= affil-num=10 en-affil=Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Health & Sports Sciences, Faculty of Education, Tokyo Gakugei University kn-affil= en-keyword=(+)-Terrein kn-keyword=(+)-Terrein en-keyword=Brown adipose tissue kn-keyword=Brown adipose tissue en-keyword=Thermogenesis kn-keyword=Thermogenesis en-keyword=Obesity kn-keyword=Obesity en-keyword=PPARγ kn-keyword=PPARγ END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Amino Acid Substitutions in Loop C of Arabidopsis PIP2 Aquaporins Alters the Permeability of CO2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The transport of CO2 across biomembranes in plant cells is essential for efficient photosynthesis. Some aquaporins capable of CO2 transport, referred to as ‘COOporins’, are postulated to play a crucial role in leaf CO2 diffusion. However, the structural basis of CO2 permeation through aquaporins remains largely unknown. Here, we show that amino acids in loop C are critical for the CO2 permeability of Arabidopsis thaliana PIP2 aquaporins. We found that swapping tyrosine and serine in loop C to histidine and phenylalanine, which differ between AtPIP2;1 and AtPIP2;3, altered CO2 permeability when examined in the Xenopus laevis oocyte heterologous expression system. AlphaFold2 modelling indicated that these substitution induced a conformational shift in the sidechain of arginine in the aromatic/arginine (ar/R) selectivity filter and in lysine at the extracellular mouth of the monomeric pore in PIP2 aquaporins. Our findings demonstrate that distal amino acid substitutions can trigger conformational changes of the ar/R filter in the monomeric pore, modulating CO2 permeability. Additionally, phylogenetic analysis suggested that aquaporins capable of dual water/CO2 permeability are ancestral to those that are water-selective and CO2-impermeable, and CO2-selective and water impermeable. en-copyright= kn-copyright= en-aut-name=TaniaShaila Shermin en-aut-sei=Tania en-aut-mei=Shaila Shermin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UtsugiShigeko en-aut-sei=Utsugi en-aut-mei=Shigeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsuchiyaYoshiyuki en-aut-sei=Tsuchiya en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasanoShizuka en-aut-sei=Sasano en-aut-mei=Shizuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatsuharaMaki en-aut-sei=Katsuhara en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriIzumi C. en-aut-sei=Mori en-aut-mei=Izumi C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Arabidopsis thaliana kn-keyword=Arabidopsis thaliana en-keyword=CO2 transport kn-keyword=CO2 transport en-keyword=monomeric pore kn-keyword=monomeric pore en-keyword=PIP2 aquaporin kn-keyword=PIP2 aquaporin en-keyword=Xenopus laevis kn-keyword=Xenopus laevis END