Wiley Acta Medica Okayama 1467-7644 2026 Rice EMF3 Alleles Adjust Flower Opening Time to Enhance the Seed Setting Rate Under High Temperature Stress EN Takuma Ishizaki Tropical Agriculture Research Front, Japan International Research Center for Agricultural Sciences (JIRCAS) Yoichi Hashida Faculty of Agriculture, Takasaki University of Health and Welfare Hideyuki Hirabayashi Institute of Crop Science, National Agriculture and Food Research Organization (NARO) Kazuhiro Sasaki Biological Resources and Post-Harvest Division, Japan International Research Center for Agricultural Sciences (JIRCAS) Hiroki Tokunaga Tropical Agriculture Research Front, Japan International Research Center for Agricultural Sciences (JIRCAS) Eliza Vie M. Simon‐Ada Plant Breeding, Genetics, and Biotechnology Division, International Rice Research Institute (IRRI) Masataka Wakayama Institute for Advanced Biosciences, Keio University Toshiyuki Takai Plant Breeding, Genetics, and Biotechnology Division, International Rice Research Institute (IRRI) Hiroki Saito Tropical Agriculture Research Front, Japan International Research Center for Agricultural Sciences (JIRCAS) Atsushi J. Nagano Institute for Advanced Biosciences, Keio University Hitoshi Sakakibara Graduate School of Bioagricultural Sciences, Nagoya University Mikiko Kojima RIKEN Center for Sustainable Resource Science Yumiko Takebayashi RIKEN Center for Sustainable Resource Science Sung‐Ryul Kim Rice Breeding Innovations Department, International Rice Research Institute (IRRI) Ryo Matsushima Institute of Plant Science and Resources, Okayama University Michael J. Thomson Plant Breeding, Genetics, and Biotechnology Division International Rice Research Institute (IRRI) Metro Manila Philippines Kazuhiko Sugimoto Institute of Crop Science, National Agriculture and Food Research Organization (NARO) Ken‐Ichiro Hibara 18Graduate School of Agricultural Regional Vitalization, Kibi International University Tsutomu Ishimaru Biological Resources and Post-Harvest Division, Japan International Research Center for Agricultural Sciences (JIRCAS) To safeguard global food security against rapid population growth and a warming world, the effective genetic improvement of cereals is imperative. Flower opening time (FOT) critically affects the seed setting rate. In this study, we identified a gene, EARLY-MORNING FLOWERING 3 (EMF3), in which single-nucleotide substitutions strongly modulate FOT in rice in a semi-dominant manner, resulting in wide variation in FOT from earlier to later FOT than the wild-type. EMF3 knock-out mutants showed significantly reduced FOT synchrony and disrupted anther dehiscence, leading to fertilisation failure. EMF3 encodes a plasma membrane-localised polypeptide of 723 amino acids with an armadillo repeat fold and four transmembrane segments. Furthermore, EMF3 is specifically expressed in the anthers starting from nighttime on the day of flowering, with substantial impacts on the transcriptomes of both anther and lodicule, which suggested an exclusive role of EMF3 in flowering events. Modifying EMF3 alleles of O. sativa enabled the adjustment of FOT among Oryza species and subspecies, potentially facilitating cross-fertilisation by overcoming one of the major challenges of inter-specific hybridisation to exploit heterosis. Introducing the EMF3 alleles with the earlier FOT into popular rice cultivars resulted in flowering at an earlier time of day when the temperature was cooler, efficiently increasing seed setting rate under heat stress. This discovery unveils the novel mechanism of anther control of flower opening time through the EMF3 gene, while also enabling the use of EMF3 alleles in breeding strategies for efficient fertilisation for increasing hybrid rice seed production and mitigating future heat-stress damage at flowering. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1434-193X 2026 Informatics‐Driven and Automated Optimization in Flow Electrochemical Synthesis e202501237 EN Eisuke Sato Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Akine Tani Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tomohiro Nakahama Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koichi Mitsudo Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Seiji Suga Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Electrochemical synthesis has emerged as a powerful platform for environmentally sustainable chemical transformations. When integrated with flow chemistry, electrosynthetic processes exhibit enhanced scalability, making them suitable for industrial applications. Recently, the integration of electrochemical flow systems with informatics techniques has accelerated the optimization of reaction conditions. Data-driven strategies facilitate rapid exploration of multidimensional parameter spaces, enabling identification of optimal reaction conditions with high efficiency. These advances have enabled the development of automated optimization systems. This review highlights recent progress in combining electrosynthesis, flow chemistry, and computational tools, focusing on representative examples that illustrate efficient optimization protocols and autonomous reaction development. By showcasing these developments, we discuss how the integration of these technologies is driving innovation in electrochemical synthesis. No potential conflict of interest relevant to this article was reported.

The Company of Biologists Acta Medica Okayama 2046-6390 15 2 2026 Gap junction-mediated signaling coordinates Rhodopsin coupling for Drosophila color vision bio062463 EN Xuanshuo Zhang Division of Biological Sciences, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ryoki Shinjo Division of Biological Sciences, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Manabu Kitamata Division of Health Science, Advanced Comprehensive Research Organization, Teikyo University Shinichi Otsune Division of Biological Sciences, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hideki Nakagoshi Division of Biological Sciences, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The Drosophila compound eye is composed of approximately 800 ommatidia, and every ommatidium contains eight photoreceptor cells, six outer cells (R1-R6) and two inner cells (R7 and R8), and accessory cells (cone and pigment cells). The expression of rhodopsin genes in R7 and R8 is highly coordinated through an instructive signal from R7 to R8. The activity of the homeodomain protein Defective proventriculus in R1 is also required to transmit this instructive signal, suggesting that cell–cell communication between R7, R1, and R8 is important to generate the pattern of Rh expression in R7/R8 (Rhodopsin coupling). As cell junctions play crucial roles in maintaining the structural and functional integrity of tissues, we tested whether cell junction proteins are involved in the interactions between photoreceptor cells. Here, we demonstrate that gap junction proteins innexin 2 and innexin 7 in accessory cells are necessary for transmitting signals from R7 to R8. In addition, Notch-mediated accessory cell development and Rhodopsin coupling in R7/R8 are highly correlated. Our results provide evidence that functional coupling of two different neurons, R7 and R8, is established through gap junction-mediated signaling from adjacent accessory cells. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2073-4360 18 7 2026 Effect of Universal Adhesives on Resin Cement–Fiber Post–Core Materials 810 EN Masao Irie Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiro Okada Department of Dental Biomaterials, Graduate School of Dentistry, Tohoku University Yukinori Maruo Department of Prosthodontics, Okayama University Kenraro Akiyama Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kumiko Yoshihara Health Research Institute, National Institute of Advanced Industrial Science and Technology Akimasa Tsujimoto Department of Operative Dentistry, School of Dentistry, Aichi Gakuin University Takuya Matsumoto Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University This study evaluated eleven resin cements used as core build-up materials by examining the following properties: (a) push-out force between root dentin and the fiber post; (b) pull-out force between the fiber post and the core build-up material; (c) shear bond strength of the resin cement to root dentin; (d) flexural strength of the resin cement; and (e) flexural modulus of elasticity of the resin cement. The purpose of this investigation was to clarify the relationships between recently available universal adhesives, core build-up materials, resin cements, and fiber posts. All experiments were performed at two evaluation periods: after 1 day of water storage (Base) and after 20,000 thermocycles (TC 20k). For the push-out test, simulated post spaces were prepared in single-rooted human premolars. The specimens were sectioned perpendicular to the long axis into 2 mm-thick slices and then subjected to push-out testing to assess the bond strength of the dentin–resin cement–fiber post complex. No significant differences in bonding performance were found between Base and TC 20k. These findings suggest that universal adhesives used for pretreatment of multiple substrates in fiber post cementation can provide not only strong but also durable adhesion over time. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2688-4046 6 3 2026 PPy‐Coated Wire Actuators for the Micromechanostimulation of Cells: Fabrication and Characterization e202500639 EN Amaia B. Ortega‐Santos Sensor and Actuator Systems, Department of Physics Chemistry and Biology (IFM), Linköping University Satoru Hayano Department of Orthodontics, Okayama University Hospital Emilio Satoshi Hara Advanced Research Center for Oral and Craniofacial Sciences Dental School, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jose G. Martínez Sensor and Actuator Systems, Department of Physics Chemistry and Biology (IFM), Linköping University Hiroshi Kamioka Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Edwin W. H. Jager Sensor and Actuator Systems, Department of Physics Chemistry and Biology (IFM), Linköping University Cellular mechanotransduction signals play a crucial role in physiological and pathological conditions, including skeletal disorders. Although various systems exist to mechanically stimulate cultured cells, most are constrained by incubator incompatibility, limited physiological relevance, nonuniform stimulation, or complexity. The objective of this article is to develop and validate a compact, incubator-compatible tool capable of delivering localized and physiologically relevant mechanical stimulation to small cell populations. Here, we introduce a polypyrrole-based wire-shaped microactuator designed to induce localized mechanical stress to adjacent cells. These wire-shaped microactuators are biocompatible, easy-to-use, and compact for use within standard in vitro cell culture systems. Using a noncontact optical method, we characterize the actuation of polypyrrole-coated wires in an aqueous NaDBS electrolyte, showing radial expansion of 1.5–8 µm depending on the deposited polypyrrole film thickness, comparable to cellular dimensions. Next, the actuation is confirmed to be robust and stable to use in cell culture media at physiological temperature. To evaluate biological relevance, osteoblastic KUSA-A1 cells are mechanically stimulated inside the incubator and transcriptomic changes are assessed. Mechanical stimulation resulted in upregulation of genes previously associated with mechanotransduction, including Fos and Fosb. Additionally, several uncharacterized long noncoding RNAs are differentially expressed, suggesting potential novel players in the mechanotransduction pathway. No potential conflict of interest relevant to this article was reported.

岡山大学大学院ヘルスシステム統合科学研究科 Acta Medica Okayama 2436-3227 6 2026 2025 年度における「先進病院実習」の取り組み 49 57 EN Mizuki MORITA Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masaki MAGARI Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jin Wang Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toyohiko WATANABE Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masataka OITA Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Nahoko HARADA Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Keisuke SHISHIDO Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University 10.18926/interdisciplinary/70330 No potential conflict of interest relevant to this article was reported.

岡山大学大学院ヘルスシステム統合科学研究科 Acta Medica Okayama 2436-3227 6 2026 わが国のアドバンス・ケア・プランニングにおける地域住民への動機づけと評価についてのナラティブ・レビュー 39 47 EN Takako HASUI Japanese Red Cross Hokkaido College of Nursing Naoko NAKAYAMA Kanagawa University of Human Services 10.18926/interdisciplinary/70329 No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2397-4648 11 1 2026 Band-selective plasmonic polaron in thermoelectric semimetal Ta2PdSe6 with ultra-high power factor 23 EN Daiki Ootsuki Research Institute for Interdisciplinary Science, Okayama University Akitoshi Nakano Present address: Department of Applied Physics, Nagoya University Urara Maruoka Present address: Department of Applied Physics, Nagoya University Takumi Hasegawa Graduate School of Advanced Science and Engineering, Hiroshima University Masashi Arita Research Institute for Synchrotron Radiation Science, Hiroshima University Miho Kitamura Present address: NanoTerasu Center, National Institutes for Quantum Science and Technology (QST) Koji Horiba Present address: NanoTerasu Center, National Institutes for Quantum Science and Technology (QST) Teppei Yoshida Graduate School of Human and Environmental Studies, Kyoto University Ichiro Terasaki Present address: Department of Applied Physics, Nagoya University We report the electronic structure of the thermoelectric semimetal Ta2PdSe6 with a large thermoelectric power factor and giant Peltier conductivity by means of angle-resolved photoemission spectroscopy (ARPES). The ARPES spectra reveal the coexistence of a sharp hole band with a light electron mass and a broad electron band with a relatively heavy electron mass, which originate from different quasi-one-dimensional (Q1D) chains in Ta2PdSe6. Moreover, the electron band around the Brillouin-zone (BZ) boundary shows a replica structure with respect to the energy originating from plasmonic polarons due to electron-plasmon interactions. The different scattering effects and interactions in each atomic chain lead to asymmetric transport lifetimes of carriers: a large Seebeck coefficient can be realized even in a semimetal. Our findings pave the way for exploring the thermoelectric materials in previously overlooked semimetals and provide a new platform for low-temperature thermoelectric physics, which has been challenging with semiconductors. No potential conflict of interest relevant to this article was reported.

Japanese Society for Medical and Biological Engineering Acta Medica Okayama 2187-5219 15 2026 Verification of a Skin Electrical Impedance Model for Evaluating Indicators of Skin Barrier Function of Older Adults 160 164 EN Osamu UEHARA Medical Engineering Laboratory, ALCARE Co., Ltd. Yuya FUNAKI Medical Engineering Laboratory, ALCARE Co., Ltd. Takao NAKAMURA Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Skin barrier function has been quantitatively evaluated through trans-epidermal water loss, which has been difficult to measure in clinical settings owing to environmental factors and the measurement time. The thickness and surface water content of the stratum corneum are important indicators of skin barrier function, and current methods for measuring these two indicators are also difficult to implement in clinical settings. Therefore, we developed a model based on skin electrical impedance to estimate the thickness and water content of the stratum corneum, enabling measurement and estimation of these two indicators in a short time. In this study, we verified this model implemented in a portable skin electrical impedance measurement device for estimating the thickness and surface water content of the stratum corneum of the skin in older adults. Thirty-four older individuals were studied. The measurement electrodes were placed in contact with the forearm skin, and an alternating signal of two frequencies was applied to measure the impedance, from which the thickness and surface water content of the stratum corneum were estimated in approximately 5 s. The correlation coefficients between the estimated and measured thickness and between the estimated and measured surface water content were 0.732 and 0.604, respectively. Furthermore, the root mean square errors of the residuals for the thickness and surface water content were 1.66 µm and 3.50 points, respectively, indicating that the model accurately estimated the thickness and surface water content of the stratum corneum, even in the skin of older adults. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-3417 16 5 2026 Concentration-Dependent Synergistic Interfacial Interactions Between Multifunctional Acrylate and Silane Coupling Agents in an Organic–Inorganic Nanohybrid Material 2339 EN Yukinori Maruo Department of Prosthodontics, Okayama University Kumiko Yoshihara Health Research Institute, National Institute of Advanced Industrial Science and Technology Masao Irie Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama University Naoki Kodama Department of Prosthodontics, Okayama University Mai Yoshizane Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kentaro Akiyama Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Synergistic effects of a multifunctional acrylate and a long-chain silane coupling agent were investigated in an organic–inorganic nanohybrid material. We tested the bond strength of nanohybrid composites treated with experimental primers containing silane coupling agents—3-methacryloxypropyl trimethoxysilane (γ-MPTS) or 8-methacryloxyoctyl trimethoxysilane (8-MOTS)—with or without multifunctional acrylates—trimethylolpropane triacrylate (A-TMPT) or dipentaerythritol hexaacrylate (A-DPH). Shear bond strength was evaluated after 24 h of water storage at 37 °C. Untreated control and silane-only groups exhibited low shear bond strengths (e.g., control: 2.4 ± 2.0 MPa) and failed exclusively at the adhesive interface. While addition of A-TMPT did not significantly improve bond strength, addition of A-DPH produced significantly higher shear bond strengths. Highest strength was achieved with 30% 8-MOTS and A-DPH (22.4 ± 6.1 MPa), followed by 20% γ-MPTS and A-DPH (19.0 ± 7.0 MPa), and A-DPH groups produced cohesive failures. Regardless of the silane used (γ-MPTS or 8-MOTS), incorporating A-DPH in the primer consistently yielded superior bond strengths, indicating a promising strategy for improved adhesion for such nanohybrid systems. These findings provide new insights into optimizing resin–filler interfacial interactions and may contribute to the development of restorative materials with improved long-term clinical durability. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0145-305X 165 2025 Local immune response induced by intra-fin antigen injection in Japanese medaka (Oryzias latipes) is a useful model for immunological studies 105344 EN Tsukasa Ryu Graduate School of Bioresource and Bioenvironmental Sciences, Laboratory of Marine Biochemistry, Kyushu University Mizuki Yoshino Graduate School of Bioresource and Bioenvironmental Sciences, Laboratory of Marine Biology, Kyushu University William Ka Fai Tse Graduate School of Bioresource and Bioenvironmental Sciences, Laboratory of Developmental Disorders and Toxicology, Kyushu University Satoshi Ansai Ushimado Marine Institute, Faculty of Science, Okayama University Taisen Iguchi Graduate School of Nanobioscience, Yokohama City University Anu Kumar Commonwealth Scientific and Industrial Research Organisation, CSIRO Environment Tomonori Somamoto Graduate School of Bioresource and Bioenvironmental Sciences, Laboratory of Marine Biochemistry, Kyushu University Miki Nakao Graduate School of Bioresource and Bioenvironmental Sciences, Laboratory of Marine Biochemistry, Kyushu University Yukiko Ogino Center for Promotion of International Education and Research, Faculty of Agriculture, Kyushu University Teleost fishes play a pivotal role in advancing our understanding of immune system evolution because they retain the ancient characteristics of vertebrate immunity, encompassing both innate and adaptive immune systems. Among these, innate immunity plays a critical role in fish as the first line of defense, coordinating rapid responses to pathogen infections. However, the lack of fish-specific immunological methodologies has limited progress in elucidating fish immune mechanisms. To better understand how the innate immune response develops and resolves in fish, detailed observation and integrative analysis of leukocytes at multiple time points is necessary. In the present study, an intra-fin injection method for observing local immune responses in Japanese medaka (Oryzias latipes) was tested and optimized to analyze the progression of zymosan-induced innate immune responses. Zymosan-injected medaka showed a rapid immune response characterized by leukocyte recruitment and phagocytosis. Using TG(FmpxP:mCherry) transgenic medaka with mCherry fluorescence driven by myeloperoxidase (mpx) promoter, granulocyte chemotaxis towards the site of zymosan entry was successfully visualized. The rapid increase in tumor necrosis factor α (tnfa), interleukin-1β (il1b), interleukin-6 (il6), and CXC motif chemokine ligand 8 (cxcl8) expressions in zymosan-injected anal fins provided a molecular basis for the visualized tissue-specific cellular response. Our study underscores the dynamic orchestration of immune components during the innate immune response in Japanese medaka and highlights their potential as a promising model for immunological research. No potential conflict of interest relevant to this article was reported.

American Society for Clinical Investigation Acta Medica Okayama 2379-3708 11 3 2025 Collagen-binding C-type natriuretic peptide enhances chondrogenesis and osteogenesis e198959 EN Kenta Hirai Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenta Sawamura Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Ryusaku Esaki Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Ryusuke Sawada Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuka Okusha Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eriko Aoyama Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Hiroki Saito Department of Orthopaedic Surgery, Kitasato University School of Medicine Kentaro Uchida Department of Orthopaedic Surgery, Kitasato University School of Medicine Takehiko Mima Department of Medical Technology, Faculty of Health Sciences, Ehime Prefectural University of Health Sciences Satoshi Kubota Department of Biochemistry and Molecular DentistryBacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shiro Imagama Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Masaki Matsushita Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Osamu Matsushita Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuyuki Hosono Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences C-type natriuretic peptide (CNP) is known to promote chondrocyte proliferation and bone formation; however, CNP’s extremely short half-life necessitates continuous intravascular administration to achieve bone-lengthening effects. Vosoritide, a CNP analog designed for resistance to neutral endopeptidase, allows for once-daily administration. Nonetheless, it distributes systemically rather than localizing to target tissues, which may result in adverse effects such as hypotension. To enhance local drug delivery and therapeutic efficacy, we developed a potentially novel synthetic protein by fusing a collagen-binding domain (CBD) to CNP, termed CBD-CNP. This fusion protein exhibited stability under heat conditions and retained the collagen-binding ability and bioactivity as CNP. CBD-CNP localized to articular cartilage in fetal murine tibiae and promoted bone elongation. Spatial transcriptomic analysis revealed that the upregulation of chondromodulin expression may contribute to its therapeutic effects. Treatment of CBD-CNP mixed with collagen powder to a fracture site of a mouse model increased bone mineral content and bone volume compared with CNP-22. Intraarticular injection of CBD-CNP to a mouse model of knee osteoarthritis suppressed subchondral bone thickening. By addressing the limitations of CNP’s rapid degeneration, CBD-CNP leverages its collagen-binding capacity to achieve targeted, sustained delivery in collagen-rich tissues, offering a promising strategy for enhancing chondrogenesis and osteogenesis. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2752-4191 5 6 2025 Sex differences in the progression of cardiovascular–kidney–metabolic syndrome oeaf162 EN Satoshi Taya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidehiro Kaneko Department of Cardiovascular Medicine, The University of Tokyo Yuta Suzuki Department of Advanced Cardiology, The University of Tokyo Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Mizuno Department of Cardiology, Medical Quality Management Office, QI Center, St. Luke's International Hospital Toshiyuki Ko Department of Cardiovascular Medicine, The University of Tokyo Takahiro Jimba Department of Cardiovascular Medicine, The University of Tokyo Tatsuhiko Azegami Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine Akira Okada Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of Tokyo Katsuhito Fujiu Department of Cardiovascular Medicine, The University of Tokyo Norifumi Takeda Department of Cardiovascular Medicine, The University of Tokyo Hiroyuki Morita Department of Cardiovascular Medicine, The University of Tokyo Kaori Hayashi Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine Koichi Node Department of Cardiovascular Medicine, Saga University Masaomi Nangaku Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine Hideo Yasunaga Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo Norihiko Takeda Department of Cardiovascular Medicine, The University of Tokyo Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aims Cardiovascular–kidney–metabolic (CKM) syndrome is a novel disease concept; however, sex differences in its progression remain uncertain. This study aimed to quantify the risk of cardiovascular disease (CVD) events across CKM stages and to explore sex differences in this association.<br> Methods and results We included 1 332 436 individuals (581 423 males and 751 013 females) from the DeSC database between 2014 and 2023 who had no prior CVD (i.e. CKM Stage 4). CKM stages were categorized as follows: Stage 0 (no CKM risk factors); Stage 1 (excess or dysfunctional adiposity); Stage 2 [metabolic risk factors and chronic kidney diseases (CKD)], and Stage 3 (subclinical CVD). We used Cox models to examine the association of CKM stages with the risk of CVD events (newly developed CKM Stage 4), including myocardial infarction, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The progression from CKM Stages 0 to 3 showed a dose-dependent increase in adjusted hazard ratios (HR) for developing CVD events, with the highest risk at Stage 3 [1.85 (95% CI: 1.80–1.90)]. A similar pattern was observed in both males and females. However, the magnitude of associations for CKM stages 1–3 differed between the sexes: HR by Stage 1, 1.12 (1.04–1.21) vs. 1.12 (1.07–1.16); by Stage 2, 1.78 (1.69–1.88) vs. 1.43 (1.39–1.48); by Stage 3, 1.99 (1.89–2.10) vs. 1.82 (1.76–1.88); and P-for-interaction values were 0.87, < 0.001, and 0.005, respectively.<br> Conclusion In this large nationwide cohort, CKM stage progression was associated with higher CVD risk in both sexes, with modest sex-specific differences. These findings highlight the value of CKM staging for early risk assessment, regardless of sex. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2026 Clinical and Genetic Landscape of Glioblastoma, IDH-Wildtype With FGFR Gene Family Alterations EN Yasuhito Kegoya Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshihiro Otani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryo Mizuta Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryosuke Ikemachi Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mako Kamiura Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Joji Ishida Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinichi Toyooka Center for Comprehensive Genomic Medicine, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Glioblastoma, isocitrate dehydrogenase wildtype (GBM, IDH-wt), is a highly aggressive brain tumor with a poor prognosis. Alterations in the fibroblast growth factor receptor (FGFR) gene family—such as FGFR::TACC fusions and FGFR1 mutations—have emerged as potential therapeutic targets; however, their clinical and genetic features in GBM, IDH-wt remain unclear. We analyzed 1076 GBM, IDH-wt cases using comprehensive genomic profiling data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database in Japan. FGFR alterations were detected in 8.0% of patients, including FGFR::TACC fusions (3.3%) and FGFR1 mutations (2.9%). The FGFR::TACC fusion-positive group was older at diagnosis and showed higher frequencies of TERT promoter mutation and MDM2 amplification, and lower frequencies of EGFR amplification and TP53 mutation, compared with the fusion-negative group. The FGFR1 mutation-positive group was enriched for ATRX, NF1, and PIK3CA mutations and had significantly fewer TERT promoter and PTEN mutations, compared with the mutation-negative group. No significant differences in overall survival were observed, although both groups tended to have longer median overall survival compared with their respective negative groups. This study represents the largest genomic cohort to date of FGFR alterations in GBM, IDH-wt. FGFR::TACC fusion-positive and FGFR1 mutation-positive GBMs exhibited distinct genetic profiles, highlighting the clinical relevance of molecular subclassification and providing insight for future therapeutic strategies. No potential conflict of interest relevant to this article was reported.

The Japanese Society for Neuroendovascular Therapy Acta Medica Okayama 1882-4072 19 1 2025 The Qualification Examination for Specialists and Instructors in the Japanese Society of Neuroendovascular Therapy: History and Current Status sr.2024-0099 EN Shinichi Yoshimura Department of Neurosurgery, Hyogo Medical University Kenji Sugiu Department of Neurological Surgery, Okayama University Graduate School of Medicine Masaru Hirohata Department of Neurosurgery, Kurume Medical University Yukiko Enomoto Department of Neurosurgery, Gifu University Graduate School of Medicine Hirotoshi Imamura Department of Neurosurgery, National Cerebral and Cardiovascular Center Wataro Tsuruta Department of Endovascular Neurosurgery, Toranomon Hospital Toshiyuki Fujinaka Department of Neurosurgery, National Hospital Organization Osaka National Hospital Hitoshi Hasegawa Department of Neurosurgery, Brain Research Institute, Niigata University Toshio Higashi Department of Neurosurgery, Fukuoka University Chikushi Hospital Takashi Izumi Department of Neurosurgery, Nagoya University of Graduate School of Medicine Hiro Kiyosue Department of Diagnostic Radiology, Kumamoto University Faculty of Life Sciences Yasushi Matsumoto Division of Development and Discovery of Interventional Therapy, Tohoku University Hospital Hidenori Oishi Oishi Neurosurgery Clinic, and Department of Neurosurgery, The Jikei University School of Medicine Tetsu Satow Department of Neurosurgery/Stroke Center, Kindai University Hospital Michihiro Tanaka Department of Neurosurgery and Neuroendovascular Surgery, Kameda Neurocenter, Kameda Medical Center Tomoyuki Tsumoto Department of Neurosurgery, Showa University Fujigaoka Hospital Hiroshi Yamagami Division of Stroke Prevention and Treatment, Institute of Medicine, University of Tsukuba Akira Ishii Department of Neurosurgery, Juntendo University Faculty of Medicine Yuji Matsumaru Department of Neurosurgery, Institute of Medicine, University of Tsukuba Shigeru Miyachi Department of Neurological Surgery, Aichi Medical Univeristy Neuroendovascular therapy is a key treatment for cerebrovascular disorders, driven by advancements in devices and techniques. The Japanese Society for Neuroendovascular Therapy (JSNET) established a certification system in 1997 to ensure operator competence and minimize complications, with the first examination in 2002. JSNET offers 2 main certifications: specialist and instructor. Specialists perform basic procedures, while instructors lead in practice, education, and research. In 2020, the mechanical thrombectomy practitioner qualification was added to promote mechanical thrombectomy. Applicants must have a JSNET membership, relevant certifications, training, and documented experience. The certification process includes rigorous written and practical examinations that now employ non-fluoroscopic models. Certification renewal every 5 years requires conference participation and a continuing education program. Public awareness and integration into stroke center designations have grown. Over 2200 specialists, including more than 500 instructors, have been certified, significantly advancing neuroendovascular therapy in Japan. JSNET aims to continue improving certification and education to maintain high standards. No potential conflict of interest relevant to this article was reported.

The Carbon Society of Japan Acta Medica Okayama 2436-5831 4 3 2025 Synthesis and applications of porous carbonaceous materials with inherited molecular structural features from the precursor molecules 179 187 EN Koki Chida Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Takeharu Yoshi Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Kazuhide Kamiya Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka Ryota Sakamoto Department of Chemistry, Graduate School of Science, Tohoku University Fumito Tani Institute for Materials Chemistry and Engineering, Kyushu University Tomoki Ogoshi Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University Hirotomo Nishihara Institute of Multidisciplinary Research for Advanced Materials, Tohoku University The carbonization of organic crystalline materials, such as metal organic frameworks and covalent organic frameworks, has emerged as a promising approach for producing functional porous carbonaceous materials. However, both the chemically defined long-term ordered structures and the local chemical structures derived from these precursor materials are generally lost, resulting in amorphous carbons. As a result, controlling the molecular-level structure of nanoporous carbons remains a significant challenge. We report a new bottom-up synthesis approach for porous carbons with a molecular-level design, involving the carbonization of well-designed precursor molecules by thermal polymerization. Among the resulting carbons, ordered carbonaceous frameworks, which contain a high-density of regularly aligned single-atomic metal species, have been identified as promising platforms for single-atom catalysts. This approach also enables the synthesis of various three-dimensional porous carbons that reflect the structural features of their precursor molecules. Recent progress in the synthesis and applications of porous carbons derived from molecular precursors is summarized, highlighting their potential for the development of functional materials. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2590-1397 28 2025 Flow diverter treatment for internal carotid artery aneurysm following management of distal cerebral aneurysms: Technical note 100540 EN Yuichi Hirata Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Hiramatsu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Sugiu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fukiko Baba Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Juntaro Fujita Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Sotome Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masato Kawakami Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryu Kimura Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Ebisudani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Haruma Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohito Hishikawa Department of Neurosurgery, Kawasaki Medical School Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: In recent years, the effectiveness of flow diverters (FDs) for the treatment of intracranial aneurysms has been reported. While FDs are effective, their deployment involves advancing a delivery wire distally, which may pose a risk if a distal aneurysm exists within the same artery. In such cases, the delivery wire could potentially perforate the distal aneurysm. Here, we present two cases of tandem aneurysms in which an internal carotid artery (ICA) aneurysm was treated with an FD following the treatment of a distal cerebral aneurysm.<br> Case description: A 44-year-old woman and a 67-year-old woman underwent magnetic resonance imaging for headache or abducens nerve palsy. In both cases, two aneurysms were revealed: one at the ICA and the other either at the middle cerebral artery or the top of the ICA. Due to the risk of perforation by the delivery wire during FD deployment, the distal aneurysms were treated first—either with surgical neck clipping or stent-assisted coil embolization. One month after the initial treatment, FD placement for the ICA aneurysm was performed as planned without complications in either case.<br> Discussion: This is the first report where tandem aneurysms were successfully treated with treatment for distal cerebral aneurysms, followed by FDs for proximal ICA aneurysms. We emphasize the potential risk of perforation of the distal aneurysm by the delivery wire during FD placement.<br> Conclusion: Treatment of distal cerebral aneurysms beforehand can help ensure the safe and effective use of FDs in patients with tandem aneurysms. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1664-462X 16 2025 Structural analysis of PSI-ACPI and PSII-ACPII supercomplexes from a cryptophyte alga Rhodomonas sp. NIES-2332 1716939 EN Wenyue Zhang Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nozomi Yonehara Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mizuki Ishii Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haowei Jiang Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Romain La Rocca Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Pi-Cheng Tsai Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hongjie Li Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koji Kato Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Fusamichi Akita Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Jian-Ren Shen Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Light energy is converted to chemical energy by two photosystems (PSI and PSII) in complex with their light-harvesting complex proteins (LHCI and LHCII) in photosynthesis. Rhodomonas is a member of cryptophyte alga whose LHCs contain unique chlorophyll a/c proteins (ACPs) and phycobiliproteins. We purified PSI-ACPI and PSII-ACPII supercomplexes from a cryptophyte Rhodomonas sp. NIES-2332 and analyzed their structures at high resolutions of 2.08 Å and 2.17 Å, respectively, using cryo-electron microscopy. These structures are largely similar to those reported previously from two other species of cryptophytes, but exhibited some differences in both the pigment locations and subunit structures. A part of the antenna subunits of both photosystems is shifted compared with the previously reported structures from other species of cryptophytes, suggesting some differences in the energy transfer rates from the antenna to the PSI and PSII cores. Newly identified lipids are found to occupy the interfaces between the antennae and cores, which may be important for assembly and stabilization of the supercomplexes. Water molecules surrounding three iron-sulfur clusters of the PSI core are found in our high-resolution structure, some of which are conserved from cyanobacteria to higher plants but some are different. In addition, our structure of PSII-ACPII lacks the subunits of oxygen-evolving complex as well as the Mn4CaO5 cluster, suggesting that the cells are in the S-growth phase, yet the PSI-ACPI structure showed the binding of PsaQ, suggesting that it is in an L-phase. These results suggest that the S-phase and L-phase can co-exist in the cryptophytic cells. The high-resolution structures of both PSI-ACPIs and PSII-ACPIIs solved in this study provide a more solid structural basis for elucidating the energy transfer and quenching mechanisms in this group of the organisms. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1546-0096 24 1 2026 TeMPRA: advancing continuing professional development in pediatric rheumatology in Japan EN Hiroyuki Wakiguchi Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine Kunio Hashimoto Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences Masato Yashiro Department of Pediatrics, Okayama University Hospital Kenichi Nishimura Department of Pediatrics, Yokohama City University Graduate School of Medicine Takasuke Ebato Department of Pediatrics, Kitasato University Keiji Akamine Department of Nephrology and Rheumatology, Tokyo Metropolitan Children’s Medical Center Yoji Uejima Division of Infectious Diseases and Immunology, Saitama Children’s Medical Center Tomomi Sato Clinical Education Center for Physicians, Shiga University of Medical Science Yuichi Yamasaki Department of Pediatrics, Kagoshima University Hospital Junko Yasumura Department of Pediatrics, Hiroshima Prefectural Hospital Organization Futabanosato Prefectural Hospital Fumiko Okazaki Department of Pediatrics, Yamaguchi University Graduate School of Medicine Toshitaka Kizawa Department of Pediatrics, Japan Community Health Care Organization Sapporo Hokushin Hospital Ryuhei Yasuoka Department of Pediatrics, Hamamatsu University School of Medicine Tomoaki Ishikawa Department of Pediatrics, Nara Medical University Takeshi Yamamoto Department of Pediatrics, Chiba University Graduate School of Medicine Yuji Fujita Department of Pediatrics, Dokkyo Medical University Naohiro Itoh Department of Pediatrics, Faculty of Medical Sciences, University of Fukui Asami Takasaki Department of Pediatrics, School of Medicine, University of Toyama Nodoka Sakurai Department of Pediatrics, NTT East Medical Center Sapporo Kazuo Suzuki Suzuki Kids Clinic Tasuku Tamai Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine Naoki Hirano Department of Public Health and Epidemiology, Faculty of Medicine, Oita University Nami Okamoto Department of Pediatrics, Osaka Rosai Hospital, Japan Organization of Occupational Health and Safety Masaki Shimizu Department of Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Background In the context of the global shortage of pediatric rheumatologists, mid-career specialists who can play key roles in regional education, research, and clinical practice have become increasingly important. In Japan, the Team of Mid-career Pediatric Rheumatologists Alliance (TeMPRA) was founded in 2014 to support continuing professional development (CPD) and foster collaboration among mid-career pediatric rheumatologists. The aim of this study was to characterize the current status and future perspectives of the TeMPRA members.<br> Methods In 2024, a cross-sectional, web-based survey was conducted among all 37 active members of the TeMPRA across Japan. Data were collected on career trajectories, educational roles, research activities, clinical practices, and international engagement. Categorical variables were compared using appropriate statistical tests, with a significance level of 0.05.<br> Results Responses were obtained from 35 members (response rate: 95%). Most respondents (71%) were affiliated with university hospitals, and 60% had > 10 years of experience in pediatric rheumatology. Compared with those working in community hospitals, respondents affiliated with university hospitals were significantly more likely to be involved in research activities (50% vs. 0%, P = 0.0261) and global professional contributions (88% vs. 0%, P < 0.0001). Overall, 54% of respondents were engaged in teaching students or early-career pediatric rheumatologists, while 43% were involved in clinical or basic research, most commonly focusing on juvenile idiopathic arthritis and systemic lupus erythematosus. Collectively, respondents were responsible for the care of 1,677 children with pediatric rheumatic diseases. While all respondents reported willingness to contribute to pediatric rheumatology at the regional level, 94% and 71% reported willingness to contribute at the national and global levels, respectively.<br> Conclusions This nationwide survey highlights the substantial educational roles, research activities, and clinical practices of mid-career pediatric rheumatologists in Japan and suggests that the TeMPRA framework can serve as a valuable model for supporting CPD and workforce sustainability. Similar alliance-based approaches may be applicable in other countries facing comparable challenges in pediatric rheumatology. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 2041-6520 17 9 2026 Gaseous CO2 electrolysis: latest advances in electrode and electrolyzer technologies toward abating CO2 emissions 4363 EN Kazuhide Kamiya Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka Sora Nakasone Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka Ryo Kurihara Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka Asato Inoue Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka Hazuki Irie Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka Shoko Nakahata Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Satoshi Taniguchi Research Institute for Chemical Process Technology, National Institute of Advanced Industrial Science and Technology (AIST), Central 5 Thuy T. H. Nguyen Research Institute for Chemical Process Technology, National Institute of Advanced Industrial Science and Technology (AIST), Central 5 Sho Kataoka Research Institute for Chemical Process Technology, National Institute of Advanced Industrial Science and Technology (AIST), Central 5 The conversion of CO2 into multicarbon (C2+) products via electrochemical reduction is considered a key technology for the sustainable production of fuels and chemicals. The performance of high-rate gaseous CO2 electrolysis is governed by interrelated factors such as the electrocatalysts, electrodes, electrolytes, and cell architectures. Despite the intensive focus on catalyst research, systematic studies addressing the other components remain scarce, leaving critical gaps in our understanding toward achieving higher performance in CO2 electrolysis systems. The nanoscale design of catalyst surface electronic structures and the macroscale design of electrodes and electrolyzer architectures both influence the overall activity of the electrochemical system. In designing macroscale components, it is necessary to establish benchmarks based on a comprehensive evaluation of CO2 emissions for the entire electrolysis process, because these parameters are directly linked to output metrics such as current density and cell voltage under practical operating conditions. This review summarizes recent advances in electrodes and electrolyzers, and through life-cycle assessment (LCA), evaluates key performance indicators (KPIs) for achieving negative emissions and assesses the current technology readiness of CO2 electrolysis. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2475-0328 9 6 2025 Surgery for Older Cancer Patients: Cross‐Organ Review and Good Practice Statement by the Japanese Geriatric Oncology Guideline Committee 1128 1136 EN Chie Tanaka Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine Takashi Ofuchi Department of Surgery, Kyushu University Beppu Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Daisuke Inoue Department of Obstetrics and Gynecology, University of Fukui Ken Sugimoto Department of General Geriatric Medicine, Kawasaki Medical School Keiko Murofushi Division of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Toru Okuyama Department of Psychiatry/Palliative Care Center, Nagoya City University West Medical Center Shigeaki Watanuki National Center for Global Health and Medicine, National College of Nursing Chiyo Imamura Advanced Cancer Translational Research Institute, Showa University Daisuke Sakai Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine Naomi Sakurai Cancer Solutions Co. Ltd Kiyotaka Watanabe Division of Medical Oncology, Department of Medicine, School of Medicine, Teikyo University Kazuo Tamura NPO Clinical Hematology/Oncology Treatment Study Group Toshiaki Saeki Breast Oncology Service, Saitama Medical University International Medical Center Hiroshi Ishiguro Breast Oncology Service, Saitama Medical University International Medical Center Background: Although the number of older people is increasing, there is a lack of evidence and insufficient consensus regarding postoperative complications and survival in older cancer patients. In this study, we conducted a literature search and systematic review focusing on the outcomes after surgery for older cancer patients.<br> Methods: Literature focusing on surgical treatment for older cancer patients was extracted from Japanese clinical practice guidelines for gastric cancer, lung cancer, colorectal cancer, liver cancer, and gynecological cancers (uterine body, uterine cervix, ovary, and external genitalia and vagina). Outcomes were reviewed, and committee members determined the strength of evidence on a four-point scale (A to D), with A being the highest and D being the lowest.<br> Results: Older cancer patients tend to have a higher incidence of postoperative complications and postoperative syndromes, and their expected survival is generally shorter compared to non-older patients. When extensive surgeries such as para-aortic lymph node dissection and/or resection with other organs are performed for older cancer patients, the postoperative mortality rates tend to increase compared to non-older patients.<br> Conclusion: Surgical treatments for older cancer patients tend to result in higher morbidity even when the patients are in good health status. Nevertheless, there is still a possibility that a certain fraction of the patients achieve treatment outcomes comparable to those of non-older patients. Therefore, surgical indication and procedure for older cancer patients should be carefully determined based on surgical invasiveness and patient tolerability. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 0094-8276 53 5 2026 Electrical Conductivity of Amorphous and Molten CaCO3 at High Pressures and Its Implications for Mantle Conductivity Anomalies e2025GL119568 EN Bin Zhao Institute for Planetary Materials, Okayama University Takashi Yoshino Institute for Planetary Materials, Okayama University Qi Chen Center for Advanced Radiation Sources, The University of Chicago Tony Yu Center for Advanced Radiation Sources, The University of Chicago Dongzhou Zhang Center for Advanced Radiation Sources, The University of Chicago Bin Chen School of Ocean and Earth Science and Technology, University of Hawaii at Manoa Yanbin Wang Center for Advanced Radiation Sources, The University of Chicago Impedance spectrometry experiments have been conducted on CaCO3 up to 15 GPa and 2,100 K to identify its state under high pressure. The melting temperature of CaCO3 was also determined by the falling of a Re sphere observed via X-ray radiography. The phase transition from aragonite to the amorphous phase does not cause a leap in the Electrical conductivity (EC), while a drastic increase in the EC, by 1.5–2.0 log units, only occurs with the onset of melting. The EC of amorphous CaCO3 is comparable to other hydrous mantle minerals at similar pressure and temperature conditions. The required fraction of amorphous CaCO3 implies that it can be excluded from the potential origins responsible for the observed high EC anomalies in the upper mantle. If the conductivity anomalies are induced by the presence of carbonate, a low-degree melting of carbonate-bearing peridotite is anticipated. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2589-5370 80 2025 Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone combined with high-dose methotrexate plus intrathecal chemotherapy for newly diagnosed intravascular large B-cell lymphoma (PRIMEUR-IVL): long-term results of a multicentre, single-arm, phase 2 trial 103078 EN Kazuyuki Shimada Department of Hematology and Oncology, Nagoya University Graduate School of Medicine Motoko Yamaguchi Department of Hematological Malignancies, Mie University Graduate School of Medicine Yachiyo Kuwatsuka Department of Advanced Medicine, Nagoya University Hospital Kosei Matsue Division of Hematology/Oncology, Internal Medicine, Kameda Medical Center Keijiro Sato Department of Hematology, Nagano Red Cross Hospital Shigeru Kusumoto Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences Hirokazu Nagai Department of Hematology, National Hospital Organization Nagoya Medical Center Jun Takizawa Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine Noriko Fukuhara Department of Hematology and Rheumatology, Tohoku University Hospital Koji Nagafuji Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine Kana Miyazaki Department of Hematology and Oncology, Mie University Graduate School of Medicine Eiichi Ohtsuka Department of Hematology, Oita Prefectural Hospital Akinao Okamoto Department of Hematology, Fujita Health University School of Medicine Yasumasa Sugita Department of Hematology, Oami Municipal Hospital Toshiki Uchida Department of Hematology and Oncology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital Satoshi Kayukawa Department of Clinical Oncology, Nagoya Memorial Hospital Atsushi Wake Department of Hematology, Toranomon Hospital Kajigaya Daisuke Ennishi Department of Hematology and Oncology, Okayama University Hospital Yukio Kondo Department of Internal Medicine, Toyama Prefectural Central Hospital Akiko Meguro Division of Hematology, Tochigi Cancer Center Yoshihiro Kin Department of Hematology, Daini Osaka Police Hospital Yosuke Minami Department of Hematology, National Cancer Center Hospital East Daigo Hashimoto Department of Hematology, Hokkaido University Faculty of Medicine, Graduate School of Medicine Takahiro Nishiyama Division of Hematology, Ichinomiya Municipal Hospital Satoko Shimada Department of Pathology and Clinical Laboratories, Nagoya University Hospital Yasufumi Masaki Department of Hematology and Immunology, Kanazawa Medical University Masataka Okamoto Department of Hematology, Fujita Health University School of Medicine Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation Hitoshi Kiyoi Department of Hematology and Oncology, Nagoya University Graduate School of Medicine Ritsuro Suzuki Department of HSCT Data Management and Biostatistics, Nagoya University School of Medicine Shigeo Nakamura Department of Pathology and Clinical Laboratories, Nagoya University Hospital Tomohiro Kinoshita Department of Hematology and Cell Therapy, Aichi Cancer Center Background Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma for which prognosis is typically poor without a timely diagnosis. To explore the safety and efficacy of standard chemotherapy combined with central nervous system (CNS)-directed therapy, we conducted a multicentre, single-arm, phase 2 trial in untreated IVLBCL patients without CNS involvement at diagnosis (PRIMEUR-IVL). In the primary analysis, the PRIMEUR-IVL study demonstrated 2-year progression-free survival (PFS) of 76% and 2-year overall survival (OS) of 92% with a low incidence (3%) of secondary CNS involvement (sCNSi).<br> Methods We present a prespecified final analysis of the PRIMEUR-IVL study including 5-year PFS, OS and cumulative incidence of sCNSi. Participants were enrolled between June 2011 and July 2016, and the data cutoff date for the final analysis was 16 November 2021. The trial was registered in the UMIN Clinical Trial Registry (UMIN000005707) and the Japan Registry of Clinical Trials (jRCTs041180165).<br> Findings With a median follow-up of 7.1 years (interquartile range 5.6–8.7), 5-year PFS in all 37 eligible patients was 68% (95% confidence interval [CI] 50%–80%) and OS was 78% (95% CI 61%–89%). No additional sCNSi was observed after the primary analysis. Severe adverse events after the primary analysis were grade 4 neutropenia (n = 1) and grade 4 myelodysplastic syndrome that did not require specific treatment (n = 1). Eight deaths occurred during the observation period after enrolment, due to primary disease (n = 6), sepsis (n = 1) and unknown sudden death (n = 1).<br> Interpretation Long-term follow-up data demonstrated durable response for PFS and OS, and low cumulative incidence of sCNSi, indicating the efficacy of standard chemotherapy combined with CNS-directed therapy for untreated IVLBCL patients.<br> Funding This study received financial support from the Japan Agency for Medical Research and Development, Center for Supporting Hematology-Oncology Studies, and National Cancer Center. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 6 2025 Retreatment With EGFR-Tyrosine Kinase Inhibitor After Disease Progression Following Gefitinib Induction and Chemoradiotherapy in EGFR-Mutant Stage III Non-small Lung Cancer: An Efficacy and Safety Analysis of the LOGIK0902/OLCSG0905 Study e86575 EN Sho Saeki Department of Respiratory Medicine, Kumamoto University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Shinya Sakata Department of Respiratory Medicine, Kumamoto University Hospital Naohiro Oda Department of Respiratory Medicine, Okayama University Hospital Koji Inoue Department of Respiratory Medicine, Kitakyushu Municipal Medical Center Tomoki Tamura Department of Respiratory Medicine, Okayama University Hospital Ryo Toyozawa Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center Daijiro Harada Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center Kentaro Tanaka Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University Koji Inoue Department of Respiratory Medicine, Ehime Prefectural Central Hospital Yoshiyuki Shioyama Radiation Oncology, Ion Beam Therapy Center, SAGA HIMAT Foundation Kenichi Gemba Department of Respiratory Medicine, Chugoku Central Hospital Tomonari Sasaki Department of Radiation Oncology, Iizuka Hospital Akihiro Bessho Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Junji Kishimoto Center for Clinical and Translational Research, Kyushu University Hospital Kuniaki Katsui Department of Radiology, Division of Radiation Oncology, Kawasaki Medical School Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Kenji Sugio Thoracic and Breast Surgery, Oita University Background and objective: We had previously conducted a phase II study (LOGIK0902/OLCSG0905 study) involving the eight-week administration of gefitinib, followed by cisplatin-based chemoradiotherapy, to treat locally advanced, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC). Despite favorable overall survival outcomes, more than half of the patients relapsed after the protocol therapy, highlighting the need to clarify the clinical significance of retreatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated the efficacy and safety of EGFR-TKI retreatment after disease progression.<br> Materials and methods: We included 14 patients who relapsed after the protocol treatment and received any type of EGFR-TKI as post-progression treatment in this sub-analysis. We evaluated the efficacy and safety of retreatment with EGFR-TKI in these patients.<br> Results: Among the 14 patients, 11 (78.6%) responded to the induction of gefitinib in the treatment protocol. After relapse, 9/14 patients (64.3%) received gefitinib, 3/14 (21.4%) received afatinib, and 2/14 (14.3%) received erlotinib monotherapy, respectively. The median duration of post-progression EGFR-TKI treatment was 17.9 (0.7-45.5) months. The overall response rate (ORR) and disease control rate were 64.3% [9/14 patients; 95% confidence interval (CI): 35.1%-87.2%] and 85.7% (12/14 patients; 95% CI: 57.2%-98.2%), respectively. The median progression-free survival (PFS) and median survival durations after the initiation of EGFR-TKI retreatment were 11.8 months (95% CI: 5.7-20.7 months) and 47.4 months (95% CI: 31.8 months to not estimable), respectively. Adverse events were comparable to those previously reported.<br> Conclusions: Patients with disease progression after protocol therapy demonstrated sensitivity to retreatment with an EGFR-TKI, with acceptable safety. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2590-1230 27 2025 Inscribed-type spherical speed reducer with uniform reduction ratio in all directions 106742 EN Seiya Naramura Faculty of Environmental, Life, Natural Science and Technology, Okayama University Koichi Tonegawa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University So Shimooka Faculty of Environmental, Life, Natural Science and Technology, Okayama University Tomoaki Yano Faculty of Environmental, Life, Natural Science and Technology, Okayama University Akio Gofuku Okayama Prefectural University Nagayoshi Kasashima National Institute of Advanced Industrial Science and Technology Tetsushi Kamegawa Faculty of Environmental, Life, Natural Science and Technology, Okayama University A spherical motor is an actuator that can generate rotational motion about all three orthogonal axes. However, it is difficult to obtain high output torque from most electromagnetic spherical motors, primarily due to limitations inherent in electromagnetic actuators, such as restricted magnetic force and thermal constraints. Since its torque cannot be increased using planar gears, spherical speed reducers that transmit rotational torque along three orthogonal axes through sphere-to-sphere contact are required. One major limitation of conventional spherical speed reducers is that their size increases significantly as the reduction ratio becomes higher. To address this issue, we propose a novel inscribed-type spherical speed reducer, in which the deceleration mechanism is integrated within the output sphere. This configuration enables a more compact design, reducing the overall size to approximately half that of conventional designs. To predict the angular velocity and transmitted torque, theoretical models for the rotation and torque transmission of the speed reducer were developed. According to the proposed model, the reduction ratio of the spherical speed reducer is 1/3. To verify the validity of these models, experiments were conducted to measure angular velocity and torque. The theoretical results agreed well with the experimental results. In addition, the theoretical torque exhibited an average relative error of 1.63 % compared to the experimental result. Therefore, it was confirmed that the rotation and torque transmission models were valid. These results demonstrate that a reduction ratio can be obtained in all directions of the 3-DOF of the spherical speed reducer, unlike conventional 1-DOF reducers. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1991-7902 21 1 2026 Piezo1-mediated mechanotransduction in cementocytes via protein kinase B and p38 mitogen-activated protein kinase signaling 57 66 EN Kaixin Xiong Department of Stomatology, Chengdu Integrated TCM and Western Medicine Hospital (Chengdu First People’s Hospital) Yukihiko Sakisaka Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Taichi Tenkumo Division of Advanced Prosthetic Dentistry, Tohoku University Graduate School of Dentistry Eiji Nemoto Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Kentaro Maruyama Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Faisal Muhammad Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Shigeki Suzuki Department of Operative Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Tada Division of Oral Microbiology and Immunology, Tohoku University Graduate School of Dentistry Satoru Yamada Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Background/purpose: Cementocytes, terminally differentiated cells embedded within cellular cementum, are morphologically similar to osteocytes; however, their mechanosensory function remains poorly understood. This study aimed to investigate whether Piezo1, a mechanosensitive ion channel, contributes to the regulation of osteo/cementogenic gene expression in murine cementocyte-like IDG-CM6 cells.<br> Materials and methods: IDG-CM6 cells were subjected to cyclic stretch or treated with Piezo1-specific agonist Yoda1 or antagonist GsMTx4. Expression levels of osteo/cementogenic genes (Wnt1, Sost, Opg) and protein levels were analyzed. The involvement of intracellular signaling pathways was assessed using pharmacological inhibitors targeting mitogen-activated protein kinase and protein kinase B (PKB/AKT) pathways.<br> Results: Cyclic stretch upregulated Wnt1 and Opg, and downregulated Sost expression, without altering Piezo1 expression, suggesting an enhanced osteo/cementogenic potential. These effects were abolished by GsMTx4 and closely mimicked by Yoda1 stimulation. The Yoda1-induced gene expression changes were transient and diminished after withdrawal. Inhibitor experiments confirmed that Piezo1-mediated gene expression is modulated primarily through the AKT and p38 signaling pathways. Phosphorylation of AKT and p38 was rapidly induced by cyclic stretch.<br> Conclusion: Our findings demonstrate that Piezo1 functions as a mechanosensor in cementocytes, modulating the expression of osteo/cementogenic genes via the AKT and p38 pathways. This study provides new insight into the molecular mechanisms of cementocyte mechanotransduction and may inform strategies for periodontal regeneration and orthodontic treatment. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2075-4418 16 4 2026 Recent Advances in Kidney Disease Diagnosis and Treatment: Bridging Molecular Insights and Clinical Practice 549 EN Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 2169-7574 14 2 2026 A Technique for Repositioning the Posteriorly Displaced Premaxilla Following Prior Repair of Complete Bilateral Cleft Lip e7467 EN Yuki Arimura Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Iida Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aiko Hyodo Advanced Cleft Lip and Cleft Palate Center, Okayama University Hospital Ayaka Mikami Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Hayano Advanced Cleft Lip and Cleft Palate Center, Okayama University Hospital Fumiko Takemoto Advanced Cleft Lip and Cleft Palate Center, Okayama University Hospital Hiroshi Kamioka Advanced Cleft Lip and Cleft Palate Center, Okayama University Hospital It is well known that osteotomy of the premaxilla is an effective surgical procedure for the correction of a displaced premaxilla in patients with bilateral cleft lip and palate. In cases with a posteriorly displaced premaxilla, it is not easy to move the premaxilla forward because of scarring of the palatal mucosal attachment, narrowing of the adjacent maxillary segments, and the stable fixation of this bone segment after its movement. This fixation is also important in cases without secondary bone grafting. We propose a new method that combines osteotomy and a method such as bone distraction for cases with significant premaxilla displacement that are difficult to repair by osteotomy alone. A conventional orthodontic palatal expander was used as the distractor. The anterior arms were bent at the posterior part of the lingual side of the anterior teeth, and a resin base was attached to the arm parts. The posterior arms were bent and waxed onto the bands of both first molars. Supportive stainless steel wire arms, which are attached to the rest of the deciduous molars, stabilize the distractor. After the osteotomy of the premaxilla, distraction was performed at a rate of 1.0 mm per day, starting the day after surgery. Because the premaxilla of patients with bilateral cleft lip and palate has undergone multiple surgical interventions, the soft tissue is not mobile, making it impossible to guide the premaxilla to an ideal position in a single stage. However, this procedure, using this semirigid distractor, makes it possible to move the osteotomized premaxilla to the planned position with firm stability. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 2026 Turning pancreatic cancer from cold to hot: the promise of a p53-expressing oncolytic adenovirus (OBP-702) EN Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Center for Innovative Clinical Medicine, Okayama University Hospital Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma Inc Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pancreatic cancer remains one of the most lethal malignancies, with limited therapeutic options and poor responsiveness to immune checkpoint inhibitors (ICIs). This resistance is largely attributed to its profoundly immunosuppressive and desmoplastic tumor microenvironment (TME), characterized by low tumor mutational burden, dense stroma, and abundant immunosuppressive cell populations. Therefore, strategies capable of enhancing tumor immunogenicity and overcoming immune evasion are urgently needed. Oncolytic virotherapy is a promising approach, offering not only tumor-selective cytotoxicity, but also potent immunomodulatory effects. Of these agents, Telomelysin (OBP-301, Suratadenoturev), a telomerase-specific oncolytic adenovirus, demonstrated clinical safety but limited efficacy in refractory tumors. To address this challenge, we developed OBP-702, a next-generation, p53-armed, oncolytic adenovirus designed to augment antitumor activity. Preclinical studies have shown that OBP-702 exerts robust cytotoxicity through multiple mechanisms, including p53-mediated apoptosis and autophagy, E1A–E2F1-mediated p21 suppression, and inhibition of oncogenic KRAS pathways. Importantly, OBP-702 induces strong immunogenic cell death, activates dendritic cells, and promotes tumor-specific T-cell responses, effectively converting immunologically “cold” pancreatic tumors into “hot” tumors. OBP-702 also remodels the immunosuppressive TME by reducing granulocyte–macrophage colony-stimulating factor (GM-CSF) secretion, suppressing myeloid-derived suppressor cells (MDSCs), and targeting stromal components, such as cancer-associated fibroblasts (CAFs). These effects contribute to enhanced responses to ICIs and standard chemotherapies. Given its multifaceted antitumor functions and ability to overcome key barriers in pancreatic cancer, OBP-702 represents a highly promising therapeutic candidate. A first-in-human clinical trial evaluating endoscopic ultrasonography-guided intratumoral injection of OBP-702 is currently in preparation, expected to advance clinical translation of this novel virotherapeutic strategy. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2079-9292 14 24 2025 An AI-Driven System for Learning MQTT Communication Protocols with Python Programming 4967 EN Zihao Zhu Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Htoo Htoo Sandi Kyaw Department of Information and Communication Systems, Okayama University I Nyoman Darma Kotama Department of Information and Communication Systems, Okayama University Anak Agung Surya Pradhana Department of Information and Communication Systems, Okayama University Alfiandi Aulia Rahmadani Department of Information and Communication Systems, Okayama University Noprianto Department of Information and Communication Systems, Okayama University With rapid developments of wireless communication and Internet of Things (IoT) technologies, an increasing number of devices and sensors are interconnected, generating massive amounts of data in real time. Among the underlying protocols, Message Queuing Telemetry Transport (MQTT) has become a widely adopted lightweight publish–subscribe standard due to its simplicity, minimal overhead, and scalability. Then, understanding such protocols is essential for students and engineers engaging in IoT application system designs. However, teaching and learning MQTT remains challenging for them. Its asynchronous architecture, hierarchical topic structure, and constituting concepts such as retained messages, Quality of Service (QoS) levels, and wildcard subscriptions are often difficult for beginners. Moreover, traditional learning resources emphasize theory and provide limited hands-on guidance, leading to a steep learning curve. To address these challenges, we propose an AI-assisted, exercise-based learning platform for MQTT. This platform provides interactive exercises with intelligent feedback to bridge the gap between theory and practice. To lower the barrier for learners, all code examples for executing MQTT communication are implemented in Python for readability, and Docker is used to ensure portable deployments of the MQTT broker and AI assistant. For evaluations, we conducted a usability study using two groups. The first group, who has no prior experience, focused on fundamental concepts with AI-guided exercises. The second group, who has relevant background, engaged in advanced projects to apply and reinforce their knowledge. The results show that the proposed platform supports learners at different levels, reduces frustrations, and improves both engagement and efficiency. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Effective Treatment of Advanced Hepatocellular Carcinoma with Extensive Peritoneal Dissemination Using Lenvatinib 69 74 EN Shinya Wakatsuki Department of Obstetrics and Gynecology, Kochi Health Sciences Center Shinya Sakamoto Department of Gastroenterological Surgery, Kochi Health Sciences Center Akiko Ueno Department of Obstetrics and Gynecology, Kochi Health Sciences Center Takaomi Namba Department of Obstetrics and Gynecology, Kochi Health Sciences Center Yorito Yamamoto Department of Obstetrics and Gynecology, Kochi Health Sciences Center Manabu Matsumoto Department of Diagnostic Pathology, Kochi Health Sciences Center Jun Iwata Department of Diagnostic Pathology, Kochi Health Sciences Center Takehiro Okabayashi Department of Gastroenterological Surgery, Kochi Health Sciences Center Case Report 10.18926/AMO/70075 Patients with hepatocellular carcinoma (HCC) and extensive peritoneal dissemination generally have a poor prognosis and are often resistant to systemic therapy. We report the case of a 47-year-old woman with HCC and massive peritoneal dissemination who presented with malignant ascites requiring repeated cell-free and concentrated ascites reinfusion therapy and peritoneovenous shunt placement, as well as malignant pleural effusion requiring pleurodesis. Combined immunotherapy with durvalumab/tremelimumab was initiated;however, disease progression was observed after three treatment courses, prompting a switch to lenvatinib therapy. Two months after initiation of lenvatinib, CT imaging demonstrated complete disappearance of arterial enhancement in the primary hepatic lesion, along with reduction in the size of peritoneal dissemination nodules. Thirteen months after switching to lenvatinib (16 months after the initial diagnosis), the alpha-fetoprotein level continued to decrease, and the disease remained stable under treatment. Despite the extremely high tumor burden, lenvatinib achieved disease stabilization and symptomatic improvement. No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 日本における「ロシアかぜ」流行の社会史的分析 ―1889 -1891 年パンデミックと日本社会― 1 19 EN Atsushi KAWAUCHI Uehiro Disaster Risk Reduction Research Division, International Research Institute of Disaster Science (IRIDeS), TOHOKU UNIVERSITY 論文 (Research article) 10.18926/70051 This study offers a social-historical analysis of the “Russian flu” pandemic in Japan (1889–1891). Due to scarce statistical data, the study relies primarily on contemporary newspapers and magazines. It identifies two distinct epidemic waves: the first in spring-summer 1890, and the second from late 1890 to spring 1891. The first wave, though widespread, was overshadowed by a concurrent cholera epidemic and caused relatively few deaths, whereas the second wave was far more lethal and generated widespread fear. At the time, influenza remained an “unknown disease”, with unclear etiology and no established treatments. People responded with diverse measures, from purchasing patent medicines and using folk remedies to symbolic practices such as "disease naming" (osome-kaze). The crisis also renewed attention to historical records of earlier influenza-like epidemics in Japan. In contrast, by the time of the later “Spanish flu” pandemic, advances in bacteriology had already rendered influenza a medically defined disease. This comparison highlights how shifting medical knowledge shaped societal responses. The findings not only corroborate previous excess-mortality analyses but also provide new historical insights into how societies have historically confronted pandemics. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2950-3299 33 4 2025 Collagen depletion by pirfenidone enhances antitumor effect of oncolytic adenovirus against peritoneal metastases of gastric cancer 201045 EN Tomohiro Okura Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yu Mikane Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ema Mitsui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Une Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Ohara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junko Ohtsuka Laboratory of Fundamental Oncology, National Cancer Center Research Institute Rieko Ohki Laboratory of Fundamental Oncology, National Cancer Center Research Institute Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Cancer-associated fibroblasts (CAFs) play a crucial role in collagen accumulation, which develops and promotes peritoneal metastasis (PM) in gastric cancer (GC). In addition, the abundant stromal collagens in the tumor microenvironment function as a physical barrier against penetration of antitumor drugs and oncolytic viruses. This study investigated whether collagen depletion by pirfenidone (PFD), an antifibrotic drug, enhances the antitumor effects of oncolytic adenoviruses. Analysis of the clinical samples revealed a significant association of high expression of collagen 1 and α-smooth muscle actin (α-SMA) with PM development and poor prognosis of advanced GC. Human and murine GC cells enhanced collagen production by fibroblasts, which was suppressed by PFD. Abundant fibroblasts and collagen inhibited the penetration of OBP-702, which reduced the antitumor effects of OBP-702 in the spheroid model. Intraperitoneal co-injection of GC cells and fibroblasts promoted the development of collagen-rich PM and reduced the antitumor effects of OBP-702 in vivo model. PFD suppressed collagen production in PM and improved viral penetration into the tumors, which enhanced the antitumor effects of OBP-702 against PM of GC. Collagen depletion by PFD enhances the penetration of OBP-702 into PM of GC, in turn enhancing the antitumor effects of OBP-702 against PM of GC. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1996-1944 19 3 2026 Effect of Surface Morphology Formed by Additive Manufacturing on the Adhesion of Dental Cements to Zirconia 563 EN Kumiko Yoshihara National Institute of Advanced Industrial Science and Technology (AIST), Health and Medical Research Institute Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Sungho Lee National Institute of Advanced Industrial Science and Technology (AIST) Yukinori Maruo Department of Prosthodontics, Okayama University Fiona Spirrett Joining and Welding Research Institute, Osaka University Soshu Kirihara Joining and Welding Research Institute, Osaka University Yasuhiro Yoshida Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Bart Van Meerbeek Department of Oral Health Sciences, BIOMAT, KU Leuven Background: Durable bonding to zirconia remains difficult because its chemically inert surface resists acid etching. Additive manufacturing (AM) enables controlled surface morphology, which may enhance micromechanical retention without additional treatments. Methods: Zirconia specimens with three AM-derived surface designs—(1) concave–convex hemispherical patterns, (2) concave hemispherical patterns, and (3) as-printed surfaces—were fabricated using a slurry-based 3D printing system and sintered at 1500 °C. Zirconia specimens fabricated by subtractive manufacturing using CAD/CAM systems, polished with 15 µm diamond lapping film and with or without subsequent alumina sandblasting, served as controls. Surface morphology was analyzed by FE-SEM, and shear bond strength (SBS) was tested after cementation with a resin-based luting agent. Results: SEM revealed regular layered textures and designed hemispherical structures (~300 µm) in AM specimens, along with step-like irregularities (~40 µm) at layer boundaries. The concave–convex AM group showed significantly higher SBS than both sandblasted and polished subtractive-manufactured zirconia (p < 0.05). Vertically printed specimens demonstrated greater bonding strength than those printed parallel to the bonding surface, indicating that build orientation affects resin infiltration and interlocking. Conclusion: AM-derived zirconia surfaces can provide superior and reproducible micromechanical retention compared with conventional treatments. Further optimization of printing parameters and evaluation of long-term durability are needed for clinical application. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 1756-2848 19 2026 Clinical efficacy and safety of endoscopic ultrasound-guided ablation therapies for pancreatic neuroendocrine tumors: a systematic review and meta-analysis EN Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Hospital Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Hospital Yasuto Takeuchi Department of Gastroenterology and Hepatology, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Background: Pancreatic neuroendocrine tumors (pNETs) are rare; however, they are increasingly being detected. Although surgical resection remains the standard treatment, its invasiveness has prompted interest in less invasive alternatives, particularly for small non-functional pNETs (NF-pNETs) and insulinomas.<br> Objectives: To evaluate the clinical efficacy and safety of endoscopic ultrasound-guided ethanol injection (EUS-EI) and radiofrequency ablation (EUS-RFA) for pNETs.<br> Design: A systematic review and meta-analysis.<br> Data sources and methods: A literature search of PubMed, MEDLINE, and Google Scholar was conducted (April 2005–April 2025). Studies were eligible if they reported clinical outcomes of EUS-EI or EUS-RFA in adult patients with insulinomas or NF-pNETs. The primary endpoints were clinical success (short-term symptom resolution or radiological response) and adverse event (AE) rates. Data were pooled using a random-effects model.<br> Results: Twenty-six studies were included in the meta-analysis. For insulinomas, the pooled clinical success rate was 77% (95% confidence interval (CI), 59–88) for EUS-EI and 95% (95% CI, 89–97) for EUS-RFA. The pooled incidence of total AEs was 32% (95% CI, 17–51) for EUS-EI and 25% (95% CI, 15–39) for EUS-RFA. For NF-pNETs, the pooled clinical success rates were 76% (95% CI, 54–90) for EUS-EI and 85% (95% CI, 74–92) for EUS-RFA, and the pooled incidence of total AEs was 27% (95% CI, 20–35) and 26% (95% CI, 17–38), respectively. The most common moderate or severe AEs were pancreatitis in 12 patients (7.6%) after EUS-EI, and pancreatic fluid collection in 4 patients (1.9%) and pancreatic duct stricture in 3 patients (1.4%) after EUS-RFA. One fatal case occurred in a 97-year-old patient following EUS-RFA.<br> Conclusion: Both EUS-EI and EUS-RFA are effective, relatively safe, and minimally invasive treatment options for pNETs. However, severe AE can occur, and careful patient selection and treatment indication are essential.<br> Trial registration: Not registered. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 3 2025 Prospective Evaluation of the Safety and Compression Performance of Novel Compression Denim Jeans in Healthy Volunteers and Patients With Lymphedema e80971 EN Daiki Ousaka Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kiyoshi Yamada Departments of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriko Sakano Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoe Kirino Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazumasa Miyake Department of Rehabilitation, Lymphedema Treatment Center, Kousei Hospital Takumi Takahashi Division of Business Management, Matsuoka Corporation Akihiro Matsuoka Division of Production Engineering, Matsuoka Corporation Shintaro Yamada Division of Sales, Kaihara Corporation Akira Shinaoka Department of Lymphatics and Edematology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Oozawa Department of Clinical Safety, Okayama University Hospital Objectives: The treatment of lower-extremity lymphedema, whether congenital or acquired, remains challenging. Long-term management aimed at reducing complications and maximizing quality of life is essential. Compression stockings are crucial in this management; however, their application is limited by patient experience (ease of wear, texture, breathability, and appearance). This highlights the need to evaluate alternative compression garments that maintain therapeutic efficacy while improving patient adherence.<br> Methods: We developed a novel compression denim product (Flow plus Jeans®) using advanced sewing technology. Its baseline performance (compression ability) was evaluated by measuring pressure gradients at three points (ankle, calf, and thigh) using a mannequin-based compression testing system and compared with those of existing stockings. Thereafter, a safety assessment was conducted on healthy volunteers to evaluate potential adverse effects, including changes in lower limb circumference, signs of deep vein thrombosis (DVT) via ultrasound, and skin complications. A clinical trial in patients with lymphedema was then performed to compare its efficacy with that of conventional compression stockings.<br> Results: Baseline performance testing with a mannequin revealed that Flow plus Jeans demonstrated compression levels and pressure gradients at three calf points comparable to those of standard compression stockings. A safety study involving nine healthy volunteers confirmed that Flow plus Jeans caused no significant changes in lower-limb circumferences after three days of wear, with no cases of DVT or skin complications. In a subsequent clinical trial involving nine female patients with lymphedema, the jeans showed non-inferiority to existing stockings concerning lower-limb circumference measurements at six points (pre-use vs. six months post-use), with patient-reported experiences assessed via questionnaires. Notably, patients reported enhanced satisfaction regarding the jeans' fashionability, which could serve as an incentive for long-term adherence.<br> Conclusion: Our findings suggest that Flow plus Jeans represent a promising novel option for the long-term management of lymphedema, offering an alternative that balances medical efficiency with improved patient satisfaction and demonstrates safety in healthy individuals. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1873-149X 33 1 2026 Bridging the Gap Between Static Histology and Dynamic Organ-on-a-Chip Models 10 EN Zheyi Wang Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiji Naruse Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Takahashi Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University For more than a century, pathology has served as a cornerstone of modern medicine, relying primarily on static microscopic assessment of tissue morphology—such as H&E staining—which remains the “gold standard” for disease diagnosis. However, this conventional paradigm provides only a snapshot of disease states and often fails to capture their dynamic evolution and complex functional mechanisms. Moreover, animal models are constrained by marked interspecies differences, creating a persistent gap in translational research. To overcome these limitations, we propose the concept of New Pathophysiology, a research framework that transcends purely morphological descriptions and aims to resolve functional dynamics in real time. This approach integrates Organ-on-a-Chip (OOC) technology, multi-omics analyses, and artificial intelligence to reconstruct the entire course of disease initiation and to enable personalized medicine. In this review, we first outline the foundations and limitations of traditional pathology and animal models. We then systematically summarize more than one hundred existing OOC disease models across multiple organs—including the kidney, liver, and brain. Finally, we elaborate on how OOC technologies are reshaping the study of key pathological processes such as inflammation, metabolic dysregulation, and fibrosis by converting them into dynamic, mechanistic disease models, and we propose future perspectives in the field. This review adopts a relatively uncommon classification strategy based on pathological mechanisms (mechanism-based), rather than organ-based categorization, allowing readers to recognize shared principles underlying different diseases. Moreover, the focus of this work is not on emphasizing iteration or replacement of existing approaches, but on preserving past achievements from a historical perspective, with an emphasis on overcoming current limitations and enabling new advances. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 2169-9313 131 1 2026 Electrical Conductivity of Carbonatite Melts to 20 GPa: Constraints on Partial Melting Atop the 410‐km Discontinuity and in the Lower Mantle Transition Zone e2025JB033390 EN Bin Zhao Institute for Planetary Materials, Okayama University Jintao Zhu Institute for Planetary Materials, Okayama University Qi Chen Center for Advanced Radiation Sources, University of Chicago Takashi Yoshino Institute for Planetary Materials, Okayama University Deep-origin carbonatite melts are considered to be the products of partial-melting of the oceanic crust in the subduction zones. In this study, we conducted electrical conductivity (EC) measurements on two samples, the composition of which resemble the partial-melting products atop the 410-km discontinuity and in the lower part of the transition zone. The EC of carbonatite melts was investigated using impedance spectroscopy combined with a multi-anvil press up to 20 GPa. Pressure has a great effect on the EC of the carbonatite melts. While the EC dropped overall by 0.6 log unit from 3 to 20 GPa for varying compositions, the pressure effect becomes weaker above 10 GPa. The Hashin-Shtrikman mixing model indicates that melt fraction of 0–0.3 vol% is necessary to account for the EC atop the 410-km discontinuity beneath NE China, north Philippine Sea, north Pacific, and Australian craton. However, this value soars to 1–4.5 vol% for the lower part of the transition zone in the same regions, and further increases to 3.7–7.3 vol% for cold subduction regions if the slab surface temperature is 300 K lower. The difference in the needed melt fraction at different depths implies that the magnitude of partial melting is much larger in the lower part of the mantle transition zone, and it is thus likely to be the main barrier to the recycled carbonates towards the deep interior. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 2050-750X 2026 Multi-step mechanisms of early phospholipid hydrolysis and mineralisation unveiled through combined quantum chemical calculations and experimental analysis EN Keisuke Shibata Department of Materials Science, Waseda University Takahumi Shiotani Department of Resources and Environmental Engineering, Waseda University Yunhao Chen Department of Materials Science, Waseda University Reina Kurihara Department of Resources and Environmental Engineering, Waseda University Katsunori Yamaguchi Department of Resources and Environmental Engineering, Waseda University Emilio Satoshi Hara Department of Advanced International and Information Dentistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nílson Kunioshi Department of Materials Science, Waseda University Phospholipids play key roles in bone formation, with phosphatidylserine (PS) reportedly inducing more rapid mineralisation than phosphatidylcholine (PC); however, the underlying mechanisms remains unclear. This study investigated PS and PC mineralisation using experimental methods and computational chemistry. The stationary points in the potential energy surfaces of the reactions were preliminarily found using a neural network potential (PreFerred Potential in Matlantis) capable of predicting the interaction energies for arbitrary combinations of atoms, and then refined through density functional theory calculations (Gaussian16, at the B3LYP/6-31G(d,p) level of theory). When hydrolysis reactions were assumed to be the initial step in the mineralisation of phospholipids, the results were consistent with empirical analysis. PS was found to be more easily hydrolised than PC, primarily owing to the presence of a labile proton in the NH3+ group of serine that facilitates proton transfer, enhancing hydrolysis of PS at lower energy thresholds. Specifically, when a single phospholipid was considered, three distinct hydrolysis routes were identified: between serine (or choline) and phosphate, between glycerol and phosphate, and between an aliphatic carbon chain and the glycerol backbone. In particular, the initial steps of hydrolysis involved the formation of a pentavalent phosphate intermediate. When calculations were performed with two adjacent phospholipid molecules, the loosely bound proton (H+) in the NH3+ group could be readily transferred either to the P–O bond linking serine to the phosphate group; or to the P–O bond connecting the phosphate to glycerol in a neighboring PS6 molecule. These findings reveal the important roles of serine NH3+ in facilitating hydrolysis of PS, and provide insights for designing novel molecules to accelerate bone regeneration. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1663-9812 16 2025 Regulatory considerations for developing phage therapy medicinal products for the treatment of antimicrobial resistant bacterial infections 1713471 EN Ai Fukaya-Shiba Office of Regulatory Science Coordination, Pharmaceuticals and Medical Devices Agency Akiko Ogata Office of Regulatory Science Coordination, Pharmaceuticals and Medical Devices Agency Ryosuke Kuribayashi Office of Cellular and Tissue-based Products, Pharmaceuticals and Medical Devices Agency Akira Sakurai Office of Cellular and Tissue-based Products, Pharmaceuticals and Medical Devices Agency Kanako Suzuki Office of Regulatory Science Coordination, Pharmaceuticals and Medical Devices Agency Shunsuke Takadama Office of New Drug IV, Pharmaceuticals and Medical Devices Agency Jihei Nishimura Office of New Drug IV, Pharmaceuticals and Medical Devices Agency Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hiroki Ohge Department of Infectious Diseases, Hiroshima University Hospital Takamasa Takeuchi Pathogen Genomics Center, National Institute of Infectious Diseases, Japan Institute for Health Security Hideyuki Tamaki Biomanufacturing Process Research Center, National Institute of Advanced Industrial Science and Technology Tetsuya Matsumoto Department of Infectious Diseases, International University of Health and Welfare Kotaro Kiga Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Hidetomo Iwano Laboratory of Veterinary Biochemistry, Rakuno Gakuen University School of Veterinary Medicine Recently, there have been growing expectations that treatment of infections with bacteriophages (phages), viruses which specifically infect bacteria, can be used as a treatment option for antimicrobial resistant bacterial infections. In Europe and the United States, in addition to phage therapy as a form of personalized medicine, development of pre-defined phage therapy medicinal products (PTMPs) is progressing, and clinical trials are underway. From October 2024 to July 2025, the Pharmaceuticals and Medical Devices Agency exchanged opinions on trends and points to consider in drug development of PTMPs used for antimicrobial resistant bacterial infections with external experts. Development of PTMPs for regulatory approval requires quality control strategies, establishment of manufacturing methods, non-clinical evaluations, and clinical trial plans based on the characteristics of the phage. In this document, based on the regulatory and development trends in Europe and the United States, the current considerations on quality, non-clinical evaluation, and clinical trial planning including the Cartagena Act in the development of PTMPs in Japan are summarized. The basic concepts presented here are intended to be applied to antimicrobial resistant bacterial infections targeted by PTMPs but can be mostly applicable to bacterial infections in general. We hope that these findings will further accelerate more active development of PTMPs towards timely patient access to innovative products. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Single cell spatial transcriptomics links Wnt signaling disruption to extracellular matrix development in a cleft palate model 29639 EN Jeremie Oliver Piña Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Resmi Raju Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Evan Stipano Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Aye Chan Myo Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Ziyi Wang Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Department of Molecular Biology and Biochemistry, Okayama University Mitsuaki Ono Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Department of Molecular Biology and Biochemistry, Okayama University Parna Chattaraj Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Masae Furukawa Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Rena N. D’Souza Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Despite advances in understanding the morphological disruptions that lead to defects in palate formation, the precise perturbations within the signaling microenvironment of palatal clefts remain poorly understood. To explore in greater depth the genomic basis of palatal clefts, we designed and implemented the first single cell spatial RNA-sequencing study in a cleft palate model, utilizing the Pax9−/− murine model at multiple developmental timepoints, which exhibits a consistent cleft palate defect. Visium HD, an emerging platform for true single-cell resolution spatially resolved transcriptomics, was employed using custom bins of 2 × 2 μm spatial gene expression data. Validation of spatial gene expression was then validated using custom designed Xenium In Situ mRNA spatial profiling and RNAscope Multiplex assays. Functional enrichment analysis revealed a palate cell-specific perturbation in Wnt signaling effector function in tandem with disrupted expression of extracellular matrix genes in developing mesenchyme. As a key step toward laying the framework for identifying key molecular targets these data can be used for translational studies aimed at developing effective therapies for human palatal clefts. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 11 2025 Perioperative Multidisciplinary Intervention Led to Complete Minimally Invasive Transthoracic Esophagectomy for a Patient With Severe Lung Dysfunction: A Case Report e97931 EN Makoto Matsumoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kento Kawasaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomoyoshi Kunitomo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Risk factors for postoperative pneumonia after esophagectomy include smoking, severe lung dysfunction, and sarcopenia. Heavy smokers often have chronic obstructive pulmonary disease (COPD), which is associated with poor physical activity and low muscle strength. Sarcopenia is also associated with decreased physical function and malnutrition. These factors lead to a close relationship between COPD and sarcopenia. This report describes the case of a 74-year-old man who presented with dysphagia and was diagnosed with advanced esophageal cancer with lymph node metastasis. Preoperative respiratory function testing showed a forced expiratory volume in one second (FEV1) of 0.76 L because of his past smoking and COPD. Multidisciplinary intervention was started, along with neoadjuvant chemotherapy. Preoperative management improved his physical function. Robot-assisted thoracoscopic subtotal esophagectomy with the patient in the prone position was performed with curative resection and no severe postoperative complications. The perioperative multidisciplinary intervention improved physical functions and enabled safe robot-assisted thoracoscopic esophagectomy for the patient with severe lung dysfunction in the prone position. This case highlights that not only respiratory status but also physical parameters should be taken into account when considering whether a patient can tolerate surgery safely. No potential conflict of interest relevant to this article was reported.

American Association for the Advancement of Science (AAAS) Acta Medica Okayama 2375-2548 11 44 2025 Structural insights into the divergent evolution of a photosystem I supercomplex in Euglena gracilis eaea6241 EN Koji Kato Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiki Nakajima Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Runa Sakamoto Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Minoru Kumazawa Institute of Low Temperature Science, Hokkaido University Kentaro Ifuku Graduate School of Agriculture, Kyoto University Takahiro Ishikawa Institute of Agricultural and Life Sciences, Academic Assembly, Shimane University Jian-Ren Shen Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Atsushi Takabayashi Institute of Low Temperature Science, Hokkaido University Ryo Nagao Faculty of Agriculture, Shizuoka University Photosystem I (PSI) forms supercomplexes with light-harvesting complexes (LHCs) to perform oxygenic photosynthesis. Here, we report a 2.82-angstrom cryo–electron microscopy structure of the PSI-LHCI supercomplex from Euglena gracilis, a eukaryotic alga with secondary green alga-derived plastids. The structure reveals a PSI monomer core with eight subunits and 13 asymmetrically arranged LHCI proteins. Euglena LHCIs bind diadinoxanthin, which is one of the carotenoids typically associated with red-lineage LHCs and is not present in the canonical LHCI belt found in green-lineage PSI-LHCI structures. Phylogenetic analysis shows that the Euglena LHCIs originated from LHCII-related clades rather than from the green-lineage LHCI group and that the nuclear-encoded PSI subunit PsaD likely originated from cyanobacteria via horizontal gene transfer. These observations indicate a mosaic origin of the Euglena PSI-LHCI. Our findings uncover a noncanonical light-harvesting architecture and highlight the structural and evolutionary plasticity of photosynthetic systems, illustrating how endosymbiotic acquisition and lineage-specific adaptation shape divergent light-harvesting strategies. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2694-2445 5 6 2025 Electronic Structure of the S1 State Manganese Cluster in Photosystem II Investigated Using Q-Band Selective Hole-Burning 660 671 EN Shinya Kosaki Department of Physics, Graduate School of Science, Nagoya University Naohiko Nakamura Department of Physics, Graduate School of Science, Nagoya University Yoshiki Nakajima Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Jian-Ren Shen Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyuki Mino Department of Physics, Graduate School of Science, Nagoya University The electronic structure of the S1 state of photosystem II (PSII) was investigated using selective hole burning of Q-band pulsed electron paramagnetic resonance. The free induction decay and spin–echo signals of the tyrosine radical YD• in the plant PSII oscillated because of the magnetic dipole–dipole interaction with the S1 state Mn cluster. The initial period was 410 ns (2.44 MHz) and was assigned to the S = 1 spin state. Based on the oscillation analysis, both Mn1 and Mn4 and both Mn2 and Mn3 were assigned as Mn(III) and Mn(IV), respectively, which is consistent with the quantum chemical calculations. The 410 ns period was accounted for in the simplified model using the isotropic spin density distribution ratio [1.6:–1.1:–1.1:1.6] for Mn1–4 ions. This oscillation was identical with that observed in the presence of methanol. The oscillation decreased in PsbP/Q- and PsbO/P/Q-depleted PSII. In Thermosynechococcus vulcanus, two periods, 390 ns (2.56 MHz) and 630 ns (1.59 MHz), were detected, indicating that the cyanobacterial S1 state includes two isomers, S = 1 and S ≥ 2 spins. The S ≥ 2 spin was not detected in PsbO/U/V-depleted PSII without polyethylene glycol. The S ≥ 2 state was consistent with the reported quantum chemical calculation using S = 3. A simplified model accounted for the S = 1 state as the spin density distribution [1.8:–1.3:–1.3:1.8] and for the S ≥ 2 state as the isotropic spin density distribution [−0.5:0.5:0.5:0.5] for Mn1–4 ions. In combination with quantum chemical calculations, the most probable protonated structure is W1 = H2O, W2 = H2O, O4 = O2–, and O5 = O2– for the S1 state. These results demonstrate that the selective hole burning method is a powerful tool to complement X-ray studies to determine the valence and protonation structure of manganese clusters, not only in the S1 state but also in higher S-states and general metal clusters, which would provide important insights into the water oxidation mechanism. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2025 Genotype–Phenotype Correlations of Li–Fraumeni Syndrome in Japan Children's Cancer Group LFS20 Study Cohort EN Fumito Yamazaki Department of Pediatrics, Keio University School of Medicine Yoshiko Nakano Department of Genetic Medicine and Services, National Cancer Center Hospital Masashi Sanada Department of Advanced Diagnosis, Clinical Research Center, NHO Nagoya Medical Center Hiroki Kurahashi Division of Molecular Genetics, Center for Medical Science, Fujita Health University Shunsuke Miyai Division of Molecular Genetics, Center for Medical Science, Fujita Health University Arisa Ueki Department of Clinical Genetic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research Yuko Watanabe Department of Pediatric Oncology, National Cancer Center Hospital Daisuke Hasegawa Department of Pediatrics, St. Luke's International Hospital Shuhei Karakawa Department of Pediatrics, Hiroshima University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Akira Hirasawa Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akiko M. Saito Clinical Research Center, NHO Nagoya Medical Center Eisuke Inoue Showa Medical University Research Administration Center, Showa Medical University Motohiro Kato Department of Pediatrics, The University of Tokyo Hiroyoshi Hattori Department of Clinical Genetics, NHO Nagoya Medical Center Li–Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by germline pathogenic variants in the TP53 gene. With the increasing use of multi-gene panel testing, TP53 variants have been identified in individuals who do not meet established TP53 testing criteria, such as the Chompret criteria. The term “attenuated LFS” has been proposed for some of these cases, particularly those with adult-onset cancer. We analyzed participants of the Japanese nationwide prospective clinical trial of the cancer surveillance program (Japan Children's Cancer Group LFS-20), along with clinical information including their family histories, to better understand their genotypic and phenotypic characteristics. We identified 32 distinct TP53 variants from 41 families (45 participants), including four missense variants with conflicting classifications of pathogenicity in ClinVar. Among these families, 36 (88%) met the LFS criteria (hereafter referred to as “LFS” in contrast to attenuated LFS), while 5 (12%) were classified as attenuated LFS. Including 30 additional family members carrying the same variant, we analyzed 75 individuals with TP53 variants. Of these, 40 with LFS and 6 with attenuated LFS had cancer. Multiple primary cancers occurred in 22 individuals (21 LFS, 1 attenuated LFS). LFS-core tumors accounted for 66% (58/88) of cancers in the LFS group and 63% (5/8) in the attenuated LFS group; of note, all core tumors in the attenuated group were limited to breast cancer. Hotspot missense variants were detected in 11 of 36 LFS families and in none of 5 attenuated LFS families, and non-hotspot null variants were found in 14 and 1, respectively. Our study revealed genotype–phenotype correlations in several respects. UMIN-CTR: UMIN000045855. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2025 Atezolizumab + Chemotherapy for Advanced Non-Small Cell Lung Cancer in Japanese Clinical Practice (J-TAIL-2) EN Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Makoto Nishio Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Atsushi Osoegawa Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine Eiki Kikuchi Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University Hideharu Kimura Department of Respiratory Medicine, Kanazawa University Hospital Yasushi Goto Department of Thoracic Oncology, National Cancer Center Hospital Junichi Shimizu Department of Thoracic Oncology, Aichi Cancer Center Hospital Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Ichiro Yoshino International University of Health and Welfare, Narita Hospital Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Yasutaka Watanabe Department of Thoracic Oncology, Saitama Cancer Center Akito Hata Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center Akira Kisohara Department of Respiratory Medicine, Kasukabe Medical Center Shoichi Kuyama Department of Respiratory Medicine, NHO Iwakuni Clinical Center Masafumi Yamaguchi Department of Thoracic Oncology, NHO Kyushu Cancer Center Asako Miwa Chugai Pharmaceutical Co., Ltd. Shunichiro Iwasawa Chugai Pharmaceutical Co., Ltd. Misa Tanaka Chugai Pharmaceutical Co., Ltd. Akihiko Gemma Nippon Medical School First-line atezolizumab combination therapies were approved for the treatment of metastatic non-small cell lung cancer (NSCLC) based on results from the global phase 3 trials IMpower130, IMpower132, and IMpower150. These trials reported 12-month overall survival (OS) rates of 60%–67% with atezolizumab combination therapy. J-TAIL-2 (NCT04501497), a prospective, multicenter, observational study, evaluated atezolizumab combination therapy in routine clinical practice in Japan. Patients ≥ 20 years old with NSCLC received atezolizumab plus carboplatin and nab-paclitaxel (atezo + CnP), atezolizumab plus carboplatin or cisplatin plus pemetrexed (atezo + PP), or atezolizumab plus bevacizumab plus carboplatin and paclitaxel (atezo + bev + CP) in clinical practice. The primary endpoint was the 12-month OS rate. Secondary endpoints included OS, progression-free survival, and subgroup analyses, including IMpower-unlike (did not meet the main eligibility criteria of each IMpower trial) and IMpower-like patients. In total, 814 patients were enrolled (atezo + CnP, n = 217; atezo + PP, n = 211; atezo + bev + CP, n = 386). The IMpower-unlike group included patients with Eastern Cooperative Oncology Group performance status ≥ 2, autoimmune disease, or interstitial lung disease. Twelve-month OS rates (95% confidence interval [CI]) were 62.9% (55.8–69.2), 72.1% (65.2–77.9), and 68.3% (63.2–72.9) with atezo + CnP, atezo + PP, and atezo + bev + CP, respectively. OS hazard ratios (95% CI) in the IMpower-unlike vs. -like subgroups were 1.36 (0.91–2.05), 1.08 (0.70–1.68), and 1.49 (1.09–2.06), respectively. No new safety signals were observed. Real-world efficacy and safety for each atezolizumab combination were comparable to those in the relevant IMpower trials. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2366-1070 13 4 2025 Asian Subgroup Analysis of Patients in the Phase 2 DeLLphi-301 Study of Tarlatamab for Previously Treated Small Cell Lung Cancer 1041 1054 EN Myung-Ju Ahn Hematology-Oncology Department, Samsung Medical Center (SMC), Sungkyunkwan University School of Medicine Byoung Chul Cho Medical Oncology Department-501, ABMRC, Yonsei University Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Hiroki Izumi Thoracic Oncology, National Cancer Center Hospital East Jong-Seok Lee Hematology/Oncology, Seoul National University Bundang Hospital Ji-Youn Han Center for Lung Cancer, National Cancer Center-Graduate School of Cancer Science and Policy Chi-Lu Chiang Department of Chest Medicine, Taipei Veterans General Hospital Shuang Huang Amgen Inc. Ali Hamidi Amgen Inc. Sujoy Mukherjee Amgen Inc. Krista Lin Xu Amgen Asia Pacific Pte. Ltd. Hiraoki Akamatsu Internal Medicine III, Wakayama Medical University Introduction: Tarlatamab is a bispecific T-cell engager (BiTE®) immunotherapy that binds delta-like ligand 3 on the surface of small cell lung cancer (SCLC) cells and CD3 on T cells, facilitating T cell-mediated cancer cell lysis. In the primary analysis of the phase 2 DeLLphi-301 study (NCT05060016), tarlatamab showed a favourable benefit-to-risk profile with durable objective responses and promising survival outcomes in patients with previously treated SCLC. Here, phase 2 data for the Asia region subgroup are presented.<br> Methods: Patients with previously treated, advanced SCLC received 10 mg tarlatamab every 2 weeks. The primary endpoint was objective response rate (ORR) by blinded independent central review (RECIST version 1.1). Key secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety. The present analysis includes patients enrolled at sites in Asia.<br> Results: A total of 43 patients were enrolled at sites in Asia. ORR was 46.3% (95% confidence interval [CI], 30.7–62.6) and median DOR was 7.2 months (95% CI 3.9 to not estimable). The median follow-up was 16.6 months for PFS and 21.2 months for OS. Median PFS was 5.4 months (95% CI 3.0–8.1) and median OS was 19.0 months (95% CI 11.4 to not estimable). The most common treatment-emergent adverse event (AE) was cytokine release syndrome (48.8%), and all such events were grade 1 or 2. There were no discontinuations due to treatment-related AEs.<br> Conclusions: Tarlatamab demonstrated durable responses and promising survival outcomes with a manageable safety profile in this post hoc analysis of patients from Asia with previously treated SCLC.<br> Trial Registration: ClinicalTrials.gov, NCT05060016. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0732-8893 113 4 2025 Time to positivity for differentiating blood culture contamination: A 20-hour cutoff for major contaminants 117030 EN Yohei Manabe Department of Pharmacy, Okayama University Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Kenta Nakamoto Department of Infectious Diseases, Okayama University Hospital Kohei Oguni Department of Infectious Diseases, Okayama University Hospital Hidemasa Akazawa Department of Infectious Diseases, Okayama University Hospital Yasushi Fujita Department of Nursing, Okayama University Hospital Takashi Kiguchi Department of Nursing, Okayama University Hospital Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Background: Blood culture remains the gold standard for diagnosing bacteremia; however, contamination inevitably occurs in 2-3% of cases, requiring differentiation between true bacteremia and contamination. Although time to positivity (TTP) aids in this clinical decision, with detection after 24 hours generally indicating contamination, technological advances in blood culture systems may have shortened this threshold interval.<br> Methods: This study retrospectively analyzed blood culture data in our hospital from April 2023 to January 2025 to determine the optimal TTP cutoff. Patients with positive blood cultures for major contaminating bacteria were included. Cases were classified as true bacteremia or contamination based on a comprehensive chart review conducted by the antimicrobial stewardship audit, and TTP was compared between the groups. Sensitivity, specificity, and Youden index at various TTP cutoffs were utilized to determine the optimal threshold using the receiver operating characteristic curve analysis.<br> Results: Seventy-one patients were enrolled, with 34 cases classified as true bacteremia and 37 as contamination. Identified bacteria included coagulase-negative staphylococci (70.4%), viridans group streptococci (18.3%), and others (11.3%). The median TTP was significantly shorter in the true bacteremia group compared with the contamination group (18.6 vs.25.8 hours, p < 0.001). In the contamination group, 43.2% of the cases demonstrated positive growth within 24 hours. Based on sensitivity, specificity, and Youden index, the optimal threshold was estimated to be 20 hours. A subgroup analysis of the CNS-only cohort yielded concordant results.<br> Conclusion: This study suggests that a 20-hour TTP threshold could help effectively differentiate true bacteremia from contamination in current clinical settings. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2772-5723 5 2 2026 Feasibility and Diagnostic Utility of Mucosal T-Cell Flow Cytometry for Intestinal Graft-Versus-Host Disease 100820 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takumi Kondo Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daisuke Ennishi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nobuharu Fujii Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mai Hiramatsu Division of Medical Support, Okayama University Hospital Araki Hirabata Division of Medical Support, Okayama University Hospital Takahide Takahashi Division of Medical Support, Okayama University Hospital Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background and Aims: Timely diagnosis of intestinal complications after hematopoietic stem cell transplantation (HSCT), including graft-versus-host disease (GVHD), transplant-associated thrombotic microangiopathy, and cytomegalovirus infection, is essential for appropriate management. This study evaluated whether mucosal T-cell profiling from endoscopic biopsies could support the diagnosis of these post-transplant conditions.<br> Methods: We prospectively analyzed 58 intestinal biopsy specimens from 21 post-HSCT patients. Paired samples were obtained from the stomach and duodenum during upper endoscopy and from the ileum and large intestine during colonoscopy. Lymphocytes were isolated from each specimen and analyzed using flow cytometry. These data were integrated with those of a previously collected cohort (35 patients, 51 samples) for comparative immunophenotypic analysis across histologically defined groups.<br> Results: Duodenal biopsies yielded more lymphocytes than did gastric biopsies (mean ± standard deviation: 532 ± 823 vs 233 ± 392 cells; P = .070), with comparable yields between the ileum and colon. Among 41 evaluable cases, the CD56+:CD3+ ratio was significantly lower in patients with GVHD (5.5 ± 2.2%) than in those with nonspecific or no inflammation (28.4 ± 16.3%; P = .006). A cutoff value of <11% provided 85.7% sensitivity and 83.3% specificity for diagnosing GVHD (area under the curve = 0.91).<br> Conclusion: Mucosal T-cell profiling using endoscopic biopsies is feasible and may aid in the diagnosis of GVHD after HSCT. A decreased CD56+:CD3+ ratio is a promising marker for distinguishing GVHD from other post-transplant intestinal conditions. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1340-6868 32 6 2025 Clinical significance on switching CDK4/6 inhibitors among 13,284 patients with metastatic breast cancer 1405 1416 EN Takuya Nishina Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Maki Tanioka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kenji Takada Medical AI Project, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takahiro Tsukioki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yuko Takahashi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tadahiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Recent clinical trials have shown that switching to a combination therapy of a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) prolongs progression-free survival (PFS) compared with ET monotherapy. Reports indicate that abemaciclib provides benefits regardless of the PIK3CA mutation status; however, its clinical benefits remain insufficient. This study aimed to evaluate the clinical significance of switching CDK4/6i + ET in a large real-world cohort. Using a medical database, we identified 13,284 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer who received CDK4/6i + ET between 2008 and 2022. Patients were categorized into five groups based on their first- and second-line therapy patterns. We compared the median time to discontinuation (TTD) among the groups. In patients who switched from one CDK4/6i + ET to another CDK4/6i + ET, the second-line TTD and total TTD of first- and second-line therapies (n = 542) were significantly longer than those in patients who switched from CDK4/6i + ET to ET monotherapy (n = 490) (the second-line TTD: 11.2 vs. 4.9 months, p < 0.01; total TTD: 25.1 vs. 20.5 months, p < 0.01). The order of palbociclib and abemaciclib administration did not significantly affect the second-line or total TTD in patients who switched from one CDK4/6i + ET to another CDK4/6i + ET. Switching from one CDK4/6i + ET to another CDK4/6i + ET resulted in a significantly longer TTD than switching to ET monotherapy. Considering the phase III clinical trial results of capivasertib, switching to CDK4/6i + ET is a viable therapeutic option regardless of the PIK3CA mutation status. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2405-6316 36 2025 A multi-institutional dummy run on segmentation variability and plan quality of stereotactic body radiotherapy for oligometastatic disease 100857 EN Hideaki Hirashima Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University Yukinori Matsuo Department of Radiation Oncology, Kindai University Faculty of Medicine Satoshi Ishikura Department of Radiation Oncology, St. Luke’s International Hospital, St. Luke’s International University Mitsuhiro Nakamura Department of Advanced Medical Physics, Graduate School of Medicine, Kyoto University Ikuno Nishibuchi Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University Daisuke Kawahara Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University Yoshihisa Shimada Department of Surgery, Tokyo Medical University Yoshiro Nakahara Department of Respiratory Medicine, Kitasato University Hospital Teiji Nishio Medical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of Osaka Naoto Shikama Department of Radiation Oncology, Juntendo University Graduate School of Medicine Shun-ichi Watanabe Department of Thoracic Surgery, National Cancer Center Hospital Isamu Okamoto Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University Toshiyuki Ishiba Department of Breast Surgery, Institute of Science Tokyo Fumikata Hara Department of Breast Oncology, Aichi Cancer Center Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Takashi Mizowaki Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University Background and purpose: Oligometastatic disease represents limited metastatic burden, and local ablative therapies such as stereotactic body radiotherapy (SBRT) may improve survival. However, inter-institutional variability in target segmentation and treatment planning can compromise treatment quality. This study aimed to evaluate the segmentation variability and dose distribution quality of SBRT in oligometastatic settings using a multi-institutional dummy run approach.<br> Methods and materials: Sixty-nine institutions were provided with two anonymized cases of adrenal and spine metastases to delineate targets and organs at risk (OARs) and create intensity-modulated radiotherapy plans following a protocol. Variability was quantified using the Dice similarity coefficient (DSC), Hausdorff distance, and mean distance to agreement. Plan qualities were assessed using the Paddick conformity index, modified gradient index, and a new three-dimensional conformity–gradient index (3D-CGI). Knowledge-based planning (KBP) was applied to explore potential improvements in OAR sparing.<br> Results: All submitted plans met protocol dose constraints. However, substantial segmentation variability was observed, particularly for the spine case. Among 136 plans, 79% demonstrated acceptable conformity and dose gradients, with 3D-CGI < 6 correlating with favorable distributions. Mean DSC was 0.93 for the clinical target volume and 0.76 for the cauda equina, which showed the highest variability. KBP reduced OAR doses for the adrenal case but showed limited impact for the spine case.<br> Conclusions: Although dose constraints were achieved, segmentation variability remained substantial, particularly for the cauda equina in the spine case. These findings emphasize inter-institutional differences and the need for standardization and tools to improve SBRT consistency. No potential conflict of interest relevant to this article was reported.

Japan Radioisotope Association Acta Medica Okayama 0033-8303 75 1 2026 自然起源放射性物質（NORM）を用いた232Th/212Pbジェネレーターによる短寿命放射性核種の作製—非密封放射性同位元素の安全取扱実習への応用— 13 19 EN Yui Imada Advanced Science Research Center, Okayama University Midori Isobe Advanced Science Research Center, Okayama University Hiroaki Terato Advanced Science Research Center, Okayama University Tadashi Hanafusa Advanced Science Research Center, Okayama University 我々は自然起源放射性物質（NORM）を放射線源とする232Th/212Pbジェネレーターを作製した。ジェネレーターから室温で約500 Bqの高純度の212Pbをミルキングできた。これを用いて32Pを用いた非密封放射性同位元素の安全取扱実習を置き換えることができることを示した。ジェネレーターの作製の容易さ，ミルキング操作の簡便性，212Pb及びその子孫核種の放射性同位元素としての特性から，今回作製した232Th/212Pbジェネレーターは放射線教育に有効に活用できると結論した。 No potential conflict of interest relevant to this article was reported.

Tech Science Press Acta Medica Okayama 1546-2226 85 2 2025 A Spectrum Allocation and Security-Sensitive Task Offloading Algorithm in MEC Using DVS 3437 3455 EN Xianwei Li School of Computer and Information Engineering, Bengbu University Bo Wei Faculty of Environmental, Life, Natural Science and Technology, Okayama University Xiaoying Yang School of Information Engineering, Suzhou University Amr Tolba Computer Science and Engineering Department, College of Applied Studies, King Saud University Zijian Zeng Institute of Computer Science and Digital Innovation, UCSI University Osama Alfarraj Computer Science and Engineering Department, College of Applied Studies, King Saud University With the advancements of the next-generation communication networking and Internet of Things (IoT) technologies, a variety of computation-intensive applications (e.g., autonomous driving and face recognition) have emerged. The execution of these IoT applications demands a lot of computing resources. Nevertheless, terminal devices (TDs) usually do not have sufficient computing resources to process these applications. Offloading IoT applications to be processed by mobile edge computing (MEC) servers with more computing resources provides a promising way to address this issue. While a significant number of works have studied task offloading, only a few of them have considered the security issue. This study investigates the problem of spectrum allocation and security-sensitive task offloading in an MEC system. Dynamic voltage scaling (DVS) technology is applied by TDs to reduce energy consumption and computing time. To guarantee data security during task offloading, we use AES cryptographic technique. The studied problem is formulated as an optimization problem and solved by our proposed efficient offloading scheme. The simulation results show that the proposed scheme can reduce system cost while guaranteeing data security. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 137 3 2025 呼吸器外科領域におけるロボット支援手術の進化と展望 132 136 EN Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1465-3249 27 8 2025 Clinical outcomes of Japanese patients treated with out-of-specification tisagenlecleucel in a phase 3b trial 938 943 EN Koji Kato Department of Hematology, Oncology, and Cardiovascular Medicine, Kyushu University Hospital Jun Kato Division of Hematology, Department of Medicine, Keio University School of Medicine Hideki Goto Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital Takeshi Kobayashi Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Yoshiyuki Takahashi Department of Pediatrics, Nagoya University Graduate School of Medicine Emiko Sakaida Department of Hematology, Chiba University Hospital Hidefumi Hiramatsu Department of Pediatrics, Graduate School of Medicine, Kyoto University Masahide Yamamoto Department of Hematology, Institute of Science Tokyo Hospital Satoshi Yoshihara Department of Hematology, Hyogo Medical University Hospital Jun Ando Department of Cell Therapy and Transfusion Medicine, Juntendo University Graduate School of Medicine Katsuyoshi Koh Department of Hematology/Oncology, Saitama Children’s Medical Center Kentaro Fukushima Department of Hematology and Oncology, Osaka University Graduate School of Medicine Fumiko Iwamoto Medical Affairs, Novartis Pharma K.K. Ranjan Tiwari Development Advance Quantitative Sciences, Novartis Healthcare Private Limited Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Background: The final manufactured tisagenlecleucel product should meet the commercial product release specifications to ensure the quality in terms of safety, purity, identity, and potency. However, it may occasionally fail to meet these specifications due to the nature of patient-derived cells with variable properties as starting material and the complex manufacturing process. The final product that does not meet at least one of the commercial release specifications is referred to as “out-of-specification” (OOS). However, the benefit-risk profile of OOS tisagenlecleucel has not yet been fully elucidated.<br> Aims: To evaluate the safety and efficacy of OOS tisagenlecleucel in Japanese patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) and B-cell acute lymphoblastic leukemia (B-ALL).<br> Methods: This is a single-arm, open-label, multicenter phase 3b study (NCT04094311). Patients consistent with label indication were enrolled and followed-up for 3 months.<br> Results: Of the 29 patients enrolled between December 2019 and May 2022 across 13 qualified sites in Japan, 28 received tisagenlecleucel, and of these, 23 had r/r DLBCL and 5 had r/r B-ALL. The primary reasons for OOS were low cell viability (15 of 24 batches) and low dose (8 of 23 batches) tisagenlecleucel in the r/r DLBCL group, and high dose (4 of 5 batches) in the r/r B-ALL group. In patients with r/r DLBCL, the grade 3 or 4 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in 3 and 1 patients, respectively. Response assessments were performed for 15 of 23 patients with r/r DLBCL: 6 achieved a complete response, and 1 achieved a partial response as the best response within 3 months.<br> Conclusions: Despite the limited patient sample size, our findings affirm that the infusion of OOS tisagenlecleucel is a viable option, with no observed increase in toxicity and outcomes comparable to those of in-specification products in clinical and real-world studies. No potential conflict of interest relevant to this article was reported.

Ceramic Society of Japan Acta Medica Okayama 1348-6535 134 1 2026 Preparation of brookite-type titanium dioxide particle layer on titanium surfaces via hydrothermal treatment and evaluation of in vitro apatite-forming ability 24 30 EN Satoshi Hayakawa Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yushi Nakamoto Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Seiya Kojima Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Takuya Kataoka Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tomohiko Yoshioka Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University In this study, we prepared a brookite-type titanium dioxide particle layer on the surface of titanium substrates via hydrothermal treatment in aqueous urea solutions containing sodium chloride (NaCl) and examined its in vitro apatite-forming ability. Increasing the urea concentration suppressed the formation of anatase-type titanium dioxide on the titanium substrate, forming a particle layer composed of pure brookite-type titanium dioxide. The size and packing density of brookite-type titanium dioxide particles formed on the titanium substrate increased with the NaCl concentration in a 7.0 mol·dm−3 urea solution. When titanium substrates hydrothermally treated in aqueous solutions of 7.0 mol·dm−3 urea and 2.0 mol·dm−3 NaCl were soaked in a simulated body fluid for various periods up to 7 d, the substrate surface was densely covered with hemispherical apatite particles (5.3 µm in diameter) within 3 d, indicating that the brookite-type titanium dioxide particle layer had an excellent apatite-forming ability comparable to that of the anatase-type titanium dioxide particle layer. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 0250-7005 46 1 2025 Near-infrared Photoimmunotherapy Targeting High-risk Human Neuroblastoma Cells Expressing GD2 25 38 EN HIROSHI NOUSO Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences HIROSHI TAZAWA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TERUTAKA TANIMOTO Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences MORIMICHI TANI Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences HINAKO WATANABE Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TAKANORI OYAMA Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences KAZUHIRO NOMA Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences SHUNSUKE KAGAWA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences HISATAKA KOBAYASHI Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health TAKUO NODA Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences SHINJI KURODA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TOSHIYOSHI FUJIWARA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Aim: Neuroblastoma (NB) is a primary malignant tumor of the peripheral sympathetic nervous system in infancy. Despite advances in treatment, the prognosis remains poor for high-risk NB patients. Although immunotherapy using anti-GD2 antibodies is available for high-risk NB, the therapeutic efficacy is insufficient. Near-infrared photoimmunotherapy (NIR-PIT) is an antitumor strategy that induces tumor-specific cytotoxicity by combining an antibody-photoabsorber conjugate (APC) with NIR light irradiation. In this study, we investigated the therapeutic efficacy of GD2-targeted NIR-PIT against human NB cells.<br> Materials and Methods: GD2 expression was analyzed on the surface of high-risk human NB cells (CHP-134, LA-N-5, IMR-32) and non-high-risk human NB cells (SK-N-SH) by flow cytometry. The APC was synthesized by incubating anti-GD2 antibody and IR700. The cytotoxic effect of GD2-targeted NIR-PIT was evaluated using the XTT assay. The distribution of dead cells within tumor spheres was evaluated using a live/dead assay. The in vivo antitumor effect of GD2-targeted NIR-PIT was assessed using a subcutaneous human NB xenograft tumor model.<br> Results: GD2 protein was expressed on the surface of CHP-134, LA-N-5, and IMR-32 cells but not SK-N-SH cells. GD2-targeted NIR-PIT significantly suppressed the viability of GD2-positive NB cells but not GD2-negative NB cells, compared to the control and monotherapy groups. GD2-targeted NIR-PIT significantly reduced the volume of GD2-positive CHP-134 tumor spheres by inducing the accumulation of dead cells. Subcutaneous CHP-134 xenograft tumor models demonstrated that GD2-targeted NIR-PIT significantly inhibited tumor growth compared with the control and monotherapy groups.<br> Conclusion: GD2-targeted NIR-PIT is a promising antitumor strategy for treating high-risk NB tumors expressing GD2. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2025 Genomic Profiling of Pediatric Solid Tumors With a Dual DNA/RNA Panel: JCCG-TOP2 Study EN Kayoko Tao Department of Pediatrics, National Cancer Center Hospital Takako Yoshioka Department of Pathology, National Center for Child Health and Development Miho Kato Department of Childhood Cancer Data Management, National Center for Child Health and Development Kazuyuki Komatsu Department of Pediatrics, Hamamatsu University School of Medicine Shinichi Tsujimoto Department of Pediatrics, Yokohama City University Kenichi Sakamoto Department of Pediatrics, Shinshu University School of Medicine Kazuki Tanimura Department of Pediatrics, National Cancer Center Hospital Minako Sugiyama Department of Pediatrics, National Cancer Center Hospital Masahiro Sekiguchi Department of Pediatrics, The University of Tokyo Yoshiko Nakano Department of Pediatrics, The University of Tokyo Yoshihiro Otani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasushi Yatabe Department of Diagnostic Pathology, National Cancer Center Hospital Akihiko Yoshida Department of Diagnostic Pathology, National Cancer Center Hospital Hajime Okita Department of Pathology, Keio University School of Medicine Junko Hirato Department of Pathology, Public Tomioka General Hospital Kenichi Kohashi Department of Pathology, Graduate School of Medicine, Osaka Metropolitan University Yukichi Tanaka Department of Pathology, Kanagawa Children's Medical Center Shinji Kohsaka Division of Cellular Signaling, National Cancer Center Research Institute Takashi Kubo Department of Clinical Genomics, National Cancer Center Research Institute Kuniko Sunami Department of Laboratory Medicine, National Cancer Center Hospital Makoto Hirata Department of Genetic Medicine and Services, National Cancer Center Hospital Shuichi Tsutsumi Genome Science & Medicine Division, Research Center of Advanced Science and Technology, The University of Tokyo Hiroyuki Aburatani Genome Science & Medicine Division, Research Center of Advanced Science and Technology, The University of Tokyo Katsuyoshi Koh Department of Hematology and Oncology, Saitama Children's Medical Center Masahiro Hirayama Department of Pediatrics, Mie University Graduate School of Medicine Shuhei Karakawa Department of Pediatrics, Hiroshima University Hospital Yukayo Terashita Department of Pediatrics, Hokkaido University Hospital Hiroyuki Fujisaki Department of Pediatric Hematology and Oncology, Osaka City General Hospital Takeshi Yagi Okinawa Prefectural Nanbu Medical Center & Children's Medical Center Akihiro Yoneda Department of Pediatric Surgery, National Center for Child Health and Development Shinji Mochizuki Department of Pediatrics, National Center for Global Health and Medicine, Japan Institute for Health Security Hiroyuki Shichino Department of Pediatrics, National Center for Global Health and Medicine, Japan Institute for Health Security Tatsuya Suzuki Department of Hematology, National Cancer Center Hospital Tetsuya Takimoto Department of Childhood Cancer Data Management, National Center for Child Health and Development Koichi Ichimura Department of Pathology, Kyorin University Faculty of Medicine Chitose Ogawa Department of Pediatrics, National Cancer Center Hospital Kimikazu Matsumoto Children's Cancer Center National Center for Child Health and Development Hitoshi Ichikawa Department of Clinical Genomics, National Cancer Center Research Institute Motohiro Kato Department of Pediatrics, The University of Tokyo To develop an optimized genomic medicine platform for pediatric cancers, a nationwide cancer genome profiling project was conducted from January 2022 to February 2023 in collaboration with the Japan Children's Cancer Group. This prospective observational study analyzed matched blood and FFPE tumor samples from patients aged 0–29 years with solid tumors. Genomic analysis used the TOP2 hybrid capture–enrichment system, targeting 737 and 455 genes in the DNA and RNA panels, along with allele-specific genome copy number alterations. A total of 210 patients from 50 institutions were enrolled across Japan (median age, 8 years; range, 0–25). Of these, 154 (77%) were enrolled at diagnosis or during/after initial treatment and 56 (27%) at disease progression or relapse. The TOP2 findings had great benefits in clarifying the diagnosis of pediatric solid tumors. Among the 204 patients with genomic results, 147 (72%) had potentially actionable findings, including diagnostic, prognostic, and therapeutic findings in 111 (54%), 61 (30%), and 64 (31%), respectively. Oncogenic fusions were noted in 45 (23%) patients. A copy number alteration was identified in at least one genomic region in 170 (83%) patients. Two patients exhibited a high tumor mutation burden. Seventeen (8%) patients harbored a germline pathogenic/likely pathogenic variant in cancer-predisposing genes. This study highlighted the feasibility of implementing a nationwide precision medicine platform and the clinical utility of the TOP2 system for pediatric cancers. The results support the integration of genomic data into the standard clinical care of pediatric patients with cancer, both at diagnosis and at relapse. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0305-1048 53 22 2025 eIF2D promotes 40S ribosomal subunit recycling during intrinsic ribosome destabilization gkaf1322 EN Kazuya Ichihara Division of Biological Science, Graduate School of Science, Nagoya University Taichi Shiraishi Division of Biological Science, Graduate School of Science, Nagoya University Yuhei Chadani Faculty of Environmental, Life, Natural Science and Technology, Okayama University Yuki Kito Division of Cell Biology, Medical Institute of Bioregulation, Kyushu University Chisa Shiraishi Division of Biological Science, Graduate School of Science, Nagoya University Mina Hirata Division of Biological Science, Graduate School of Science, Nagoya University Yuta Takahashi Division of Biological Science, Graduate School of Science, Nagoya University Akinao Kobo School of Life Science and Technology, Institute of Science Tokyo Atsushi Hatano Department of Omics and Systems Biology, Graduate School of Medical and Dental Sciences, Niigata University Masaki Matsumoto Department of Omics and Systems Biology, Graduate School of Medical and Dental Sciences, Niigata University Kodai Machida Graduate School of Engineering, University of Hyogo Hiroaki Imataka Graduate School of Engineering, University of Hyogo Atsushi Toyoda Advanced Genomics Center, National Institute of Genetics Emi Mishiro-Sato Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University Takayuki Nojima Medical Institute of Bioregulation, Kyushu University Takuhiro Ito Laboratory for Translation Structural Biology, RIKEN Center for Integrative Medical Sciences Hideki Taguchi School of Life Science and Technology, Institute of Science Tokyo Keiichi I Nakayama Division of Cell Biology, Medical Institute of Bioregulation, Kyushu University Akinobu Matsumoto Division of Biological Science, Graduate School of Science, Nagoya University Although eukaryotic initiation factor 2D (eIF2D) is implicated in translation initiation, reinitiation, and ribosome recycling, its precise role remains unclear. Here, we show that eIF2D promotes 40S ribosome recycling during intrinsic ribosome destabilization (IRD), a process in which ribosomes stochastically destabilize while translating proteins with consecutive acidic amino acids at their NH2-terminus. Unrecycled 40S ribosomes accumulate in eIF2D-deficient cells, leading to 80S ribosome stalling. Selective translation complex profiling (TCP-seq) reveals that eIF2D preferentially associates with IRD-prone regions. The winged helix domain, unique to eIF2D but absent in MCTS1–DENR, enhances its binding to 40S subunits, but likely clashes with ABCE1 during stop-codon-associated recycling. Loss of eIF2D reduces the expression of IRD-inducing proteins, including splicing factors. Together, these findings define a previously unappreciated role for eIF2D in 40S recycling and clarify its mechanistic divergence from the MCTS1–DENR complex. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 12 2025 Sequential Bilateral Central Retinal Vein Occlusion With Differential Long-Term Outcomes Following Cardiac Surgery e100045 EN Toshihiko Matsuo Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama University Hospital Zenichi Masuda Cardiovascular Surgery, Okayama University Hospital Hiroki Sugiyama Cardiovascular Medicine, Okayama University Hospital Kazufumi Nakamura Cardiovascular Medicine and Center for Advanced Heart Failure, Okayama University Hospital Bilateral central retinal vein occlusion (CRVO) is rare and is associated with systemic diseases such as hypertension, diabetes, dyslipidemia, and coagulopathy. In this study, we showed that the sequential development of bilateral CRVO in an elderly patient was related to increased venous pressure in the right heart system. A 71-year-old man developed CRVO in the right eye, and one year later, he developed CRVO in the left eye. He had undergone pacemaker implantation for sick sinus syndrome 10 years earlier and had started hemodialysis three months prior for chronic renal failure, probably caused by hypertensive nephrosclerosis. The right CRVO resulted in neovascular glaucoma and loss of light perception despite intensive treatment with panretinal laser photocoagulation, intravitreal bevacizumab injection, and additional laser therapy. In contrast, the left CRVO remained at an impending stage, was treated only with panretinal laser photocoagulation, and had a favorable outcome for 11 years until his death. In retrospect, half a year after the onset of left CRVO, the patient underwent open-heart surgery to repair aortic, mitral, and tricuspid valve regurgitation through aortic valve replacement, mitral valve annuloplasty, and tricuspid valve annuloplasty, respectively. Based on the temporal sequence of events, elevated venous pressure due to right heart dysfunction may have contributed to the poor outcome of the right CRVO, whereas improvement of venous stasis after cardiac surgery may have led to the better long-term outcome of the left CRVO. Venous stasis in the right heart system should therefore be considered an underlying factor in the development of bilateral CRVO. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0167-5273 445 2026 Cardiac characteristics of Fabry disease from baseline enrolment data in a nationwide prospective Japanese registry 134071 EN Toru Kubo Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University Yuichiro Maekawa Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine Kenichi Hongo Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine Saori Yamamoto Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine Yasuhiro Izumiya Department of Cardiovascular Medicine, Osaka Metropolitan University, Graduate School of Medicine Hiroyuki Yamakawa Department of Cardiology, Keio University School of Medicine Toshiyuki Yano Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine Koji Higuchi Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University Yuki Kuramoto Department of Cardiovascular Medicine, The University of Osaka Graduate School of Medicine Naoki Nakagawa Division of Cardiology and Nephrology, Department of Internal Medicine, Asahikawa Medical University Masashi Amano Department of Heart Failure and Transplantation, National Cerebral and Cardiovascular Center Yu Yamada Department of Cardiology, Institute of Medicine, University of Tsukuba Masayoshi Oikawa Department of Cardiovascular Medicine, Fukushima Medical University Yuichiro Iida Department of Cardiovascular Medicine, Kitasato University School of Medicine Kenichi Tsujita Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Yuya Matsue Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine Hideo Izawa Department of Cardiology, Fujita Health University Atsushi Suzuki Department of Cardiology, Tokyo Women's Medical University Yuji Nagatomo Department of Cardiology, National Defense Medical College Toshiyuki Nagai Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Keisuke Kida Department of Pharmacology, St. Marianna University School of Medicine Kazuto Nakamura Department of Cardiovascular Medicine, University of Yamanashi, Faculty of Medicine Kazufumi Nakamura Center for Advanced Heart Failure, Okayama University Hospital Hiroki Ikenaga Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences Takahiro Kanda Department of Internal Medicine, Division of Cardiology, Hamamatsu Red Cross Hospital Yoshiharu Kinugasa Department of Cardiovascular Medicine and Endocrinology and Metabolism, Faculty of Medicine, Tottori University Hiromasa Ito Department of Cardiology, Mie University Hospital Kenji Onoue Department of Cardiovascular Medicine, Nara Medical University Hiromitsu Kanamori Department of Cardiology, Gifu University Graduate School of Medicine Hiroaki Kitaoka Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University Background: Fabry disease (FD) is an important disease in the cardiovascular field because a significant proportion of patients with FD die from cardiac lesions.<br> Methods: A multicenter prospective registration study of patients with FD throughout Japan was designed. The baseline clinical characteristics of 175 patients are presented here.<br> Results: The mean ages at enrolment and at diagnosis were 52 ± 16 and 43 ± 18 years, respectively, with men accounting for 38 % of the patients. In the cohort, 24 % of the patients had the classical hemizygote male type, whereas 14 % had the late-onset male type, and 62 % had the heterozygote female type. On electrocardiography data at enrolment in 92 patients with left ventricular hypertrophy (LVH) (maximum LV wall thickness > 12 mm), 12 % showed a short PQ interval (< 120 msec), and 33 % had a short PendQ interval (≤ 40 msec). The Sokolow-Lyon voltage was high (6.1 ± 13.1 mv). Regarding the distribution of LVH patterns, 77 % of the patients showed concentric diffuse LVH, 16 % of the patients had asymmetric septal hypertrophy, and 1 % of the patients had hypertrophy confined to the LV apex. With regard to implantation of cardiac devices, permanent pacemakers had been implanted in 5 % of the patients and defibrillators had been implanted in 12 patients (7 %), for primary prevention in nine patients and for secondary prevention in three patients.<br> Conclusion: As the first large-scale prospective registry of FD patients in Japan, this study has provided valuable baseline data for the cardiac features and management of FD. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1873-9601 19 4 2025 Interaction between nuclear‐translocated cellular communication network factor 2 and purine‐rich box 1 regulates the expression of fibrosis‐related genes e70051 EN Xuan Thi Nguyen Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Kubota Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaharu Takigawa Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan Takashi Nishida Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Cellular communication network factor 2 (CCN2) with a nuclear localization signal-like peptide is known to promote fibrosis. However, translocation of CCN2 into the nucleus and its role in fibrosis remain unclear. We hypothesized that nuclear-translocated CCN2 is associated with purine-rich box 1 (PU.1), which is a transcription factor regulating the differentiation of myofibroblasts. Western blot analysis of the cytoplasmic and nuclear fractions of cell lysate and immunofluorescence analysis revealed that CCN2 was detectable in both the cytoplasm and nuclei of murine fibroblastic NIH3T3 cells. Additionally, chromatin immunoprecipitation (IP)-PCR and an electrophoretic mobility shift assay revealed that recombinant CCN2 protein bound to the regulatory region of Spi1, which encodes PU.1. Furthermore, IP-Western blot analysis showed that CCN2 interacted with PU.1. Finally, the forced expression of both Ccn2 and Spi1 significantly promoted the production of angiotensin II, and increased fibrosis-related molecules, such as Col1a1 and Acta2, at the gene and protein levels. These findings indicate that CCN2 translocated to the nucleus interacts with PU.1 and that the complex promotes the markers of myofibroblast differentiation, suggesting that CCN2 plays an important role in fibrosis via cooperation with PU.1, as a transcription co-factor. No potential conflict of interest relevant to this article was reported.

Fuji Technology Press Ltd. Acta Medica Okayama 1883-8049 37 6 2025 Directed Poisoning Attacks on FRIT in Adaptive Cruise Control 1392 1399 EN Taichi Ikezaki Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kenji Sawada Graduate school of Mechanical Engineering, The University of Osaka Osamu Kaneko Graduate School of Informatics and Engineering, The University of Electro-Communications 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. No potential conflict of interest relevant to this article was reported.

American Astronomical Society Acta Medica Okayama 0004-637X 992 1 2025 Observing Supernova Neutrino Light Curves with Super-Kamiokande. VI. A Practical Data Analysis Technique Considering Realistic Experimental Backgrounds 27 EN Fumi Nakanishi Department of Physics, Okayama University Ken’ichiro Nakazato Faculty of Arts and Science, Kyushu University Masayuki Harada Kamioka Observatory, Institute for Cosmic Ray Research, The University of Tokyo Yusuke Koshio Department of Physics, Okayama University Ryuichiro Akaho Faculty of Science and Engineering, Waseda University Yosuke Ashida Department of Physics, Tohoku University Akira Harada National Institute of Technology, Ibaraki College Masamitsu Mori Division of Science, National Astronomical Observatory of Japan Kohsuke Sumiyoshi National Institute of Technology, Numazu College Yudai Suwa Department of Earth Science and Astronomy, The University of Tokyo Roger A. Wendell Kavli Institute for the Physics and Mathematics of the Universe (Kavli IPMU, WPI), Todai Institutes for Advanced Study, The University of Tokyo Masamichi Zaizen Department of Earth Science and Astronomy, The University of Tokyo 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. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Exacerbation of Proteinuria in a Patient with Behçet’s Disease and IgA Nephropathy Following Colchicine Discontinuation 457 461 EN Tomohiko Asakawa Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yu Katayama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yoshimasa Sakurabu Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Katsuyoshi Katayama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Onishi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Natsumi Matsuoka-Uchiyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hidemi Takeuchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Keiko Tanaka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Ryoko Umebayashi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Rika Takemoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/69849 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. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-3425 15 11 2025 Sensory Modality-Dependent Interplay Between Updating and Inhibition Under Increased Working Memory Load: An ERP Study 1178 EN Yuxi Luo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ao Guo Department of Psychology, Institute of Education, China West Normal University Jinglong Wu Faculty of Biomedical Engineering, Shenzhen University of Advanced Technology Jiajia Yang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Background/Objectives: Working memory (WM) performance relies on the coordination of updating and inhibition functions within the central executive system. However, their interaction under varying cognitive loads, particularly across sensory modalities, remains unclear. Methods: This study examined how sensory modality modulates flanker interference under increasing WM loads. Twenty-two participants performed a visual n-back task at three load levels (1-, 2-, and 3-back) while ignoring visual (within-modality) or auditory (cross-modality) flankers. Results: Behaviorally, increased WM load (2- and 3-back) led to reduced accuracy (AC) and prolonged reaction times (RTs) in both conditions. In addition, flanker interference was observed under the 2-back condition in both the visual within-modality (VM) and audiovisual cross-modality (AVM) tasks. However, performance impairment emerged at a lower load (2-back) in the VM condition, whereas in the AVM condition, it only emerged at the highest load (3-back). Significant performance impairment in the AVM condition occurred at higher WM loads, suggesting that greater WM load is required to trigger interference. Event-related potential (ERP) results showed that N200 amplitudes increased significantly for incongruent flankers under the highest WM load (3-back) in the visual within-modality condition, reflecting greater inhibitory demands. In the cross-modality condition, enhanced N200 was not observed across all loads and even reversed at low load (1-back). Moreover, the results also showed that P300 amplitude increased with load in the within-modality condition but decreased in the cross-modality condition. Conclusions: These results demonstrated that the interaction between updating and inhibition is shaped by both WM load and sensory modality, further supporting a sensory modality-specific resource allocation mechanism. The cross-modality configurations may enable more efficient distribution of cognitive resources under high load, reducing interference between concurrent executive demands. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0264-1275 260 2025 An entangled material made from fiber aerosol deposition method 115195 EN Hongwu Yu Faculty of Environmental, Life, Natural Science and Technology, University of Okayama Naoshi Ikeda Faculty of Environmental, Life, Natural Science and Technology, University of Okayama Masakazu Mori Ryukoku University Jun Kano Faculty of Environmental, Life, Natural Science and Technology, University of Okayama Jae-Hyuk Park School of Advanced Materials Science & Engineering, Sungkyunkwan University Jun Akedo National Institute of Advanced Industrial Science and Technology This study demonstrates the successful application of Aerosol Deposition (AD) technology to short carbon fibers (length < 1 mm), enabling the rapid, three-dimensional (3D) fabrication of objects with vertical growth rates up to 0.3 mm/s, a significant improvement over conventional additive manufacturing. Through a series of experiments using this novel Fiber Aerosol Deposition (FAD) technology, three fiber lengths (47, 85, and 111 μm) and four substrate materials (carbon, polypropylene, polyethylene, and acrylonitrile butadiene styrene (ABS)) were investigated. Our findings indicate that both carbon substrate entanglement and fiber length critically influence deposition efficiency. Scanning electron microscopy (SEM) and X-ray computed tomography (CT) analyses reveal that during formation, longer fibers (>100 μm) initially create a cage-like framework, which is subsequently filled by shorter fibers. Density measurements and fiber distribution analysis confirmed that structures predominantly composed of shorter fibers exhibit higher packing densities, consistent with their role as filler material. These results collectively suggest that the FAD method’s formation mechanism relies on frictional entanglement rather than the room-temperature impact consolidation (RTIC) effect characteristic of traditional AD. This breakthrough presents a promising new technique for forming short fibers into functional 3D architectures, with potential applications extending to proteins, polymer fibers, and biomaterial fibers. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2042-8812 2025 12 2025 Endoscopic surgery for distal femoral physeal bar resection with computed tomography-assisted navigation: a case report rjaf972 EN Yasutaka Masada Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomonori Tetsunaga Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuki Yamada Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Inoue Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuichiro Okuda Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Yamamoto Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Matsumoto Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Tetsunaga Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Yokoyama Department of Advanced Rehabilitation Medicine for the Musculoskeletal System, Okayama University Yuki Okazaki Center for Education in Medicine and Health Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The formation of physeal bars, or bony bridges, following growth plate injuries can cause complications such as angular deformities or discrepancies in leg length. The management strategies for these depend on factors such as the bar’s location, extent, and residual growth potential. Herein, we describe the case of a 14-year-old male with a valgus knee deformity caused by a distal femoral physeal bar. The patient underwent endoscopic resection of the bar, assisted by computed tomography-based navigation and intraoperative O-arm imaging. This minimally invasive technique facilitated safe and accurate removal of the lesion with less risk of complications such as cortical perforation or injury to adjacent neurovascular structures compared to traditional approaches. The patient experienced favorable postoperative outcomes, including restored knee range of motion and full symptom resolution. This approach demonstrates the clinical value of integrating endoscopy with advanced navigation systems during the surgical treatment of physeal bars. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2155-5435 15 14 2025 Mesoporous Oxyhalide Aggregates Exhibiting Improved Photocatalytic Activity for Visible-Light H2 Evolution and CO2 Reduction 12551 12562 EN Hiroto Ueki Department of Chemistry, School of Science, Institute of Science Tokyo Toshiya Tanaka Department of Chemistry, School of Science, Institute of Science Tokyo Shuji Anabuki Graduate School of Natural Science and Technology, Okayama University Ryuichi Nakada Department of Chemistry, School of Science, Institute of Science Tokyo Megumi Okazaki Department of Chemistry, School of Science, Institute of Science Tokyo Kenta Aihara Department of Chemistry, School of Science, Institute of Science Tokyo Masashi Hattori Materials and Structures Laboratory, Institute of Integrated Research, Institute of Science Tokyo Fumitaka Ishiwari Department of Applied Chemistry, Graduate School of Engineering, Osaka University Rie Haruki Institute of Materials Structure Science, High Energy Accelerator Research Organization Shunsuke Nozawa Institute of Materials Structure Science, High Energy Accelerator Research Organization Toshiyuki Yokoi Nanospace Catalysis Unit, Institute of Integrated Research, Institute of Science Tokyo Michikazu Hara Materials and Structures Laboratory, Institute of Integrated Research, Institute of Science Tokyo Osamu Ishitani Department of Chemistry, Graduate School of Advanced Science and Engineering, Hiroshima University Akinori Saeki Department of Applied Chemistry, Graduate School of Engineering, Osaka University Akira Yamakata Graduate School of Natural Science and Technology, Okayama University Kazuhiko Maeda Department of Chemistry, School of Science, Institute of Science Tokyo Oxyhalides are promising visible-light photocatalysts for water splitting and CO2 conversion; however, those exhibiting high activity for these reactions have rarely been reported. Here, we show that using water-soluble Ti complexes as precursors in the microwave-assisted hydrothermal synthesis of the oxyhalide photocatalyst Pb2Ti2O5.4F1.2 (PTOF) resulted in the production of nanoparticulate PTOF. The primary particle size of the synthesized PTOF ranged from several tens of nanometers to several hundreds of nanometers. Using Ti-citric acid or Ti-tartaric acid complexes as precursors, the PTOF was formed as mesoporous aggregates, compared with a bulky analogue (0.5–1 μm) prepared using a TiCl4 precursor. The PTOF prepared from Ti-citric acid complex had a particle size of 50–100 nm and showed a one-order-of-magnitude greater activity for H2 evolution from an aqueous ethylenediaminetetraacetic acid solution with the aid of a Rh cocatalyst. An apparent quantum yield (AQY) of 15.4 ± 1.0% at 420 nm, which is the highest among the reported oxyhalide photocatalysts, was achieved under optimal conditions. Although excess particle size reduction of PTOF lowered the H2 evolution activity, the PTOF with the smallest possible primary particle size of 15–30 nm, prepared from Ti-tartaric acid complex, showed the highest activity toward the selective reduction of CO2 into formate in a nonaqueous environment when combined with a binuclear Ru(II) complex. The CO2 reduction AQY was 10.4 ± 1.8% at 420 nm, a record-high value among metal-complex/semiconductor binary hybrid photocatalysts. This study highlights the importance of morphological control of oxyhalides for realizing their full potential as photocatalysts for artificial photosynthesis. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2468-2942 45 2025 Neoadjuvant FOLFOXIRI for locally advanced rectal cancer: A retrospective analysis focusing on long-term anal preservation 101049 EN Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Matsumi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshitaka Kondo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiko Mori Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences To investigate the safety and efficacy of FOLFOXIRI as neoadjuvant chemotherapy (NAC) for locally advanced rectal cancer (LARC). The outcomes of preoperative and perioperative treatments, as well as long-term outcomes, were retrospectively compared between 26 patients who underwent FOLFOXIRI as NAC for LARC with cT3–4 and/or N+ at our institute between 2015 and 2022, and 31 patients with LARC who underwent neoadjuvant chemoradiotherapy (CAPOX-RT) at our institute between 2011 and 2022. Grade 3 or higher adverse events due to neoadjuvant treatment were significantly more common in the FOLFOXIRI group (11 cases, 42.3 %) than in the CAPOX-RT group (3 cases, 9.7 %), and most of these were neutropenia. Based on the postoperative pathological findings, the complete response rate was significantly lower in the FOLFOXIRI group (1 case, 3.8 %) than in the CAPOX-RT group (7 cases, 22.6 %), but there were no significant differences in the R0 resection rate, survival rate, or relapse-free survival rate. In the CAPOX-RT group, 17 patients (54.8 %) had anal preservation, and during the observation period, 4 patients required stoma construction due to loss of anal function in the late stage. In contrast, in the FOLFOXIRI group, there were no cases of loss of anal function among the 20 patients (76.9 %) who had anal preservation. FOLFOXIRI as NAC requires caution regarding hematological toxicity, but it can be an effective treatment option for patients with LARC who wish to preserve their anus. No potential conflict of interest relevant to this article was reported.

Biophysical Society of Japan Acta Medica Okayama 2189-4779 22 3 2025 Origin of the unique topology of the triangular water cluster in &lt;i&gt;Rubrobacter xylanophilus&lt;/i&gt; rhodopsin e220018 EN Tomoyasu Noji Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo Masaki Tsujimura Department of Advanced Interdisciplinary Studies, The University of Tokyo Keisuke Saito Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo Keiichi Kojima Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Sudo Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Ishikita Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo The crystal structure of Rubrobacter xylanophilus rhodopsin (RxR) reveals a triangular cluster of three water molecules (W413, W415, and W419) at the extracellular proton-release site, near Glu187 and Glu197. Using a quantum mechanical/molecular mechanical approach, we identified the structural nature of this unique water cluster. The triangular shape is best reproduced when all three water molecules are neutral H2O with protonated Glu187 and deprotonated Glu197. Attempts to place H3O+ at any of these water molecules result in spontaneous proton transfer to one of the acidic residues and significant distortion from the crystal structure. The plane defined by the triangular water cluster extends into the guanidinium plane of Arg71, with both aligned along the W413...W419 axis. This extended plane lies nearly perpendicular to a five-membered, ring-like H-bond network involving two carboxyl oxygen atoms from Glu187 and one from Glu197. The resulting bipartite planar architecture, defined by the water triangle, Arg71, and the Glu187/Glu197 network may reflect the exceptional thermal stability in RxR. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0883-2927 187 2025 Nitrogen distribution and nitrogen isotope fractionation in synthetic 2:1 phyllosilicates under hydrothermal conditions at 200 °C and saturated vapor pressure 106403 EN Jaeguk Jo Graduate School of Natural Science and Technology, Okayama University Toshiro Yamanaka Graduate School of Natural Science and Technology, Okayama University Youko Miyoshi Research Institute for Geo-Resources and Environment, Geological Survey of Japan, National Institute of Advanced Industrial Science and Technology (AIST) Masaya Suzuki Research Institute for Geo-Resources and Environment, Geological Survey of Japan, National Institute of Advanced Industrial Science and Technology (AIST) Yoshihiro Kuwahara Department of Environmental Changes, Faculty of Social and Cultural Studies, Kyushu University Isao Kadota Graduate School of Natural Science and Technology, Okayama University Hitoshi Chiba Graduate School of Natural Science and Technology, Okayama University Bum Han Lee Critical Minerals Research Center, Korea Institute of Geoscience & Mineral Resources (KIGAM) This study investigates nitrogen distribution and isotope fractionation within synthetic 2:1 phyllosilicates, simulating submarine hydrothermal environments at 200 °C and saturated vapor pressure. XRD and EDS results revealed the potential coexistence of multiple cations in the interlayer of synthetic 2:1 phyllosilicate, concurrently suggesting cation substitution in the tetrahedral and/or octahedral sheets. Meanwhile, the iron-enriched 25-5 sample exhibited restricted interlayer expansibility. NH4+ absorptions were identified in the NH4-stretching (3200–2800 cm−1) and NH4-bending (1450–1400 cm−1) regions, with wavenumber shifts indicating the influence of interlayer water removal. At pH 10.56, over 95% of nitrogen was released into the gas phase, while at pH 8.88, nitrogen proportions in the liquid and gas phases were comparable (average 48–49%). Experiments with iron at pH ∼8.80 showed that the nitrogen proportion in the gas phase (average 28%) was more than twofold lower than that in the liquid phase (average 68%). Equilibrium isotope fractionation factors indicated discernible preference for heavier nitrogen isotopes in the solid phase (αsolid-liquid = 1.009–1.021 and αsolid-gas = 1.011–1.027). The αliquid-gas range for sample 25–2 was 1.001–1.008, while that for the iron-enriched composite 25–5 was 0.997–1.010. Our experimental studies have confirmed that, in the absence of exchange interactions with external substances possessing different nitrogen isotope ratios, nitrogen isotope fractionation between ammonium and ammonia, controlled by variations in temperature and pH during mineralization, plays a crucial role in the variation of nitrogen isotope ratios. Additionally, we confirmed that metal-amines influence nitrogen isotope fractionation by modulating ammonia gas emission. These findings enhance our understanding of nitrogen cycling across the gas, liquid, and solid phases in submarine hydrothermal systems. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2574-0962 2025 Enhanced Charge-Transfer Kinetics Enabled by ZrO2–Based Dielectric Layers in Lithium-Ion Batteries EN Takashi Teranishi Graduate School of Natural Science and Technology, Okayama University Yusuke Higaki Graduate School of Natural Science and Technology, Okayama University Tomonori Imamura Graduate School of Natural Science and Technology, Okayama University Motoki Horibe Department of Advanced Ceramics, Nagoya Institute of Technology Shinya Kondo Department of Energy Engineering, Nagoya University Chinatsu Sasaoka R&D Laboratory, Nippon Denko Co., Ltd. Hikaru Hirabaru R&D Laboratory, Nippon Denko Co., Ltd. Shingo Katayama R&D Laboratory, Nippon Denko Co., Ltd. Masanobu Nakayama Department of Advanced Ceramics, Nagoya Institute of Technology Akira Kishimoto Graduate School of Natural Science and Technology, Okayama University The development of high-rate capability lithium-ion batteries (LIBs) requires suppression of charge-transfer resistance (RCT) at electrode–electrolyte interfaces. Here, zirconia-based dielectric oxides (MZ; M = Y, Gd, Sm, Er, etc.) were introduced onto LiCoO2 (LCO) surfaces as electronically and ionically insulating modifiers to accelerate interfacial ion transport. Electrochemical impedance spectroscopy showed that Y2O3 modified ZrO2 (YZ) decoration reduced RCT from 75.8 Ω in reference LCO to 38.3 Ω, accompanied by a 2.3-fold improvement in capacity retention at 20C. Density functional theory molecular dynamics (DFT–MD) simulations showed that solvated Li ions coordinate with surface oxygen atoms in discharging, and that adsorption energies are governed by local charge distributions determined by stabilizing cations. Optimal adsorption activity, and thus the lowest RCT, occurred when the surface charge corrugation was balanced. These findings provide design principles for dielectric interface engineering to enhance rate capability of LIBs. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1340-2838 32 6 2025 MedakaBase as a unified genomic resource platform for medaka fish biology dsaf030 EN Kenji Morikami Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems Yasuhiro Tanizawa Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems Masaru Yagura Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems Mika Sakamoto Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems Shoko Kawamoto Department of Genetics, Sokendai (Graduate University for Advanced Studies) Yasukazu Nakamura Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems Katsushi Yamaguchi Trans-Omics Facility, National Institute for Basic Biology Shuji Shigenobu Trans-Omics Facility, National Institute for Basic Biology Kiyoshi Naruse Laboratory of Bioresources, National Institute for Basic Biology, National Institutes of Natural Sciences Satoshi Ansai Ushimado Marine Institute, Okayama University Shigehiro Kuraku Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems 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. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1465-3621 55 5 2025 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 547 555 EN Naruto Taira Department of Breast and Thyroid Surgery, Kawasaki Medical School Naomi Kiyota Department of Medical Oncology and Hematology, Cancer Center, Kobe University Hospital Yuichiro Kikawa Department of Breast Surgery, Kansai Medical University Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Kyoko Kato Department of Medical Oncology, National Hospital Organization Nagoya Medical Center Kaoru Kubota Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Ryosuke Tateishi Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo Akinobu Nakata Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine Keiichiro Nakamura Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukiya Narita Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Hiroji Iwata Department of Advanced Clinical Research and Development, Nagoya City University Akihiko Gemma Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Kojiro Shimozuma Department of Biomed Sciences, College of Life Sciences, Ritsumeikan University Kei Muro Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine Tetsuya Iwamoto Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Yuki Takumoto Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Takeru Shiroiwa Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Takashi Fukuda Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Takuhiro Yamaguchi Division of Biostatistics, Tohoku University Graduate School of Medicine Yasuhiro Hagiwara Department of Biostatistics, Division of Health Sciences and Nursing, The University of Tokyo Graduate School of Medicine Hironobu Minami Division of Medical Oncology and Hematology, Department of Medicine, Kobe University Graduate School of Medicine 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. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0944-1174 60 12 2025 Combination chemotherapy for older patients with unresectable biliary tract cancer: a prospective observational study using propensity-score matched analysis (JON2104-B) 1584 1595 EN Satoshi Kobayashi Department of Gastroenterology, Kanagawa Cancer Center Kohei Nakachi Department of Medical Oncology, Tochigi Cancer Center Kouji Yamamoto Department of Biostatistics, Yokohama City University School of Medicine Makoto Ueno Department of Gastroenterology, Kanagawa Cancer Center Yuta Maruki Kenji Ikezawa Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute Takeshi Terashima Department of Gastroenterology, Kanazawa University Hospital Satoshi Shimizu Department of Gastroenterology, Kanazawa University Hospital Kotoe Oshima Division of Gastrointestinal Oncology, Shizuoka Cancer Center Kunihiro Tsuji Department of Gastroenterology, Ishikawa Prefectural Central Hospital Yoshiharu Masaki Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine Hidetaka Tsumura Department of Gastroenterological Oncology, Hyogo Cancer Center Taro Shibuki Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East Masato Ozaka Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research Naohiro Okano Department of Medical Oncology, Kyorin University Faculty of Medicine Yukiyasu Okamura Division of Digestive Surgery, Department of Surgery, Nihon University School of Medicine Kumiko Umemoto Department of Clinical Oncology, St. Marianna University School of Medicine Tatsunori Satoh Department of Gastroenterology, Shizuoka General Hospital Yasushi Kojima Department of Gastroenterology, National Center for Global Health and Medicine Kazuhiko Shioji Department of Gastroenterology, Niigata Cancer Center Hospital Hiroko Nebiki Department of Gastroenterology, Osaka City General Hospital Toshifumi Doi Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine Atsushi Naganuma Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center Shigeki Kataoka Department of Clinical Oncology, Graduate School of Medicine Faculty of Medicine, Kyoto University Emiri Kita Department of Gastroenterology, Chiba Cancer Center Hiroyuki Asama Department of Gastroenterology, Fukushima Medical University Kaoru Tsuchiya Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital Michiaki Unno Department of Surgery, Tohoku University Graduate School of Medicine Reiko Ashida Second Department of Internal Medicine, Wakayama Medical University Kazuyuki Matsumoto Department of Gastroenterology, Okayama University Graduate School of Medicine Izumi Ohno Department of Gastroenterology, Chiba University Graduate School of Medicine Takao Itoi Department of Gastroenterology, Tokyo Medical University Yuji Negoro Department of Oncologial Medicine, Kochi Health Sciences Center Yasunari Sakamoto Department of Gastroenterology and Hepatology, International University of Health and Welfare Atami Hospital Shiho Arima Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences Akinori Asagi Department of Gastroenterology, National Hospital Organization Shikoku Cancer Center Hiroyuki Okuyama Department of Medical Oncology, Kagawa University Hospital Yoshito Komatsu Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center Noritoshi Kobayashi Department of Oncology, School of Medicine Graduate School of Medicine, Yokohama City University Hiroaki Nagano Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine Junji Furuse Department of Gastroenterology, Kanagawa Cancer Center Background: Systemic chemotherapy with gemcitabine plus S-1 (GEM + S-1), GEM + CDDP plus S-1 (GEM + CDDP + S-1), or gemcitabine plus cisplatin (GEM + CDDP) is standard treatment for advanced biliary tract cancer (aBTC). We aimed to evaluate the efficacy and safety of combination chemotherapy in older patients with aBTC.<br> Methods: This multicenter prospective observational study (JON2104-B, UMIN000045156) included patients aged ≥ 70 years with aBTC. Inverse-probability weighting propensity-score analyses (IPW) were used to compare overall survival (OS) as the primary endpoint and progression-free survival (PFS) across treatment groups.<br> Results: This study included 305 patients between August 2021 and January 2023. Of them, 75, 131, 26, 52, and 10 received GEM + CDDP + S-1, GEM + CDDP, GEM + S-1, gemcitabine, and S-1; their median ages were 74, 75, 77.5, 80, and 80 years, and approximately 24%, 16.8%, 23.1%, 9.6%, and 0% had G-8 scores of > 14, respectively. GEM + CDDP had a safety profile comparable to that of GEM + CDDP + S-1 but was more toxic than gemcitabine. Per IPW, the hazard ratio (HR) for GEM + CDDP + S-1 versus GEM + CDDP was 0.80 for OS (95% confidence interval [CI], 0.55–1.17) and 0.55 for PFS (95% CI 0.38–0.80). The HR for GEM + CDDP versus gemcitabine was 0.74 for OS (95% CI 0.42–1.29) and 0.79 for PFS (95% CI 0.42–1.49).<br> Conclusions: GEM + CDDP + S-1 was associated with longer PFS without additional toxicity than GEM + CDDP for fit older patients. However, the OS for both were not statistically different. The efficacies of GEM + CDDP and gemcitabine for vulnerable older patients did not also differ significantly. These findings highlight the importance of vulnerability in patients with aBTC. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0915-5635 2025 EUS-Guided Versus Percutaneous Transhepatic Drainage of Liver Abscesses: A Multicenter Endohepatology Study in Western Japan (EPIC-LA Study) EN Takeshi Ogura Pancreatobiliary Advanced Medical Center, Osaka Medical and Pharmaceutical University Hospital Taira Kuroda Gastroenterology Center, Ehime Prefectural Hospital Takanori Matsuura Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine Jun Kitadai Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine Koh Kitagawa Department of Gastroenterology, Nara Medical University Masahiro Itonaga Second Department of Internal Medicine, Wakayama Medical University Kotaro Takeshita Department of Gastroenterology, Tane General Hospital Tomoaki Matsumori Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine Tomoya Emori Department of Gastroenterology, Wakayama Rosai Hospital Mamoru Takenaka Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine Graduate School of Medical Sciences Hajime Imai Department of Gastroenterology, Okanami General Hospital Koichiro Mandai Department of Gastroenterology, Kyoto Second Red Cross Hospital Shuhei Shintani Department of Gastroenterology, Shiga University of Medical Science Nao Fujimori Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University Hideyuki Shiomi Division of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo Medical University Masanori Asada Department of Gastroenterology and Hepatology, Japanese Red Cross Osaka Hospital Ryota Sagami Department of Gastroenterology, Faculty of Medicine, Oita University Hirotsugu Maruyama Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University Tsukasa Ikeura Division of Gastroenterology and Hepatology, Kansai Medical University Hospital Masaaki Shimatani Department of Gastroenterology and Hepatology, Kansai Medical University Medical Center Hidefumi Nishikiori Department of Gastroenterology, Oita San-ai Medical Center Kazuyuki Matsumoto Department of Endoscopy, Okayama University Hospital Masahito Kokubu Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine Hideki Kamada Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University Yusuke Ishida Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University Akitoshi Hakoda 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University Masayuki Kitano Second Department of Internal Medicine, Wakayama Medical University 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.<br> 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.<br> 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).<br> Conclusions: EUS-LAD using a metal stent might be one of the options, but further randomized, controlled trials are needed. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 64 23 2025 A Prompt Diagnosis of Ascites and Dramatic Effect of Alectinib for Advanced Lung Adenocarcinoma Harboring EML4-ALK Fusion 3413 3418 EN Takahiro Baba Department of Respiratory Medicine, Okayama University Hospital Hirofumi Inoue Department of Medical Support, Okayama University Hospital Hiromi Matsuoka Department of Medical Support, Okayama University Hospital Mio Kyakuno Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine Yusuke Yoshinaga Department of Respiratory Medicine, Okayama University Hospital Tetsuya Takeguchi Department of Respiratory Medicine, Okayama University Hospital Miho Fujiwara Department of Respiratory Medicine, Okayama University Hospital Kotaro Yamada Department of Respiratory Medicine, Okayama University Hospital Eri Nakamura Department of Respiratory Medicine, Okayama University Hospital Ayako Morita Department of Respiratory Medicine, Okayama University Hospital Naofumi Hara Department of Respiratory Medicine, Okayama University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Hisao Higo Department of Respiratory Medicine, Okayama University Hospital Masanori Fujii Department of Geriatric Medicine, Okayama University Hospital Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Kammei Rai Center for Innovative Clinical Medicine, Okayama University Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Masahiro Tabata Center for Clinical Oncology, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yosuke Togashi Department of Respiratory Medicine, Okayama University Hospital Go Makimoto Department of Respiratory Medicine, Okayama University Hospital A 75-year-old never-smoker woman presented with dyspnea and loss of appetite. A mass was identified in the left upper lobe of the lung, and the patient was referred to our hospital. Despite the diagnosis of lung adenocarcinoma via bronchoscopy, anaplastic lymphoma kinase (ALK) immunostaining was negative. Rapid weight gain and abdominal distension caused by ascites prompted fluid testing using the AmoyDx® Pan Lung Cancer PCR Panel. EML4-ALK fusion was confirmed, and alectinib therapy was initiated immediately. The tumor size had decreased significantly, and the patient was discharged on day 34. This case highlights the necessity of multiplex genetic testing even when ALK immunostaining is negative. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1470-160X 177 2025 Long-term effects of forest growth dynamics and climate change on groundwater recharge and evapotranspiration in a steep catchment of western Japan 113652 EN Rendilicha Halake Guyo Graduate School of Environmental and Life Science, Okayama University Kunyang Wang Graduate School of Advanced Science and Engineering, Hiroshima University Shin-ichi Onodera Graduate School of Advanced Science and Engineering, Hiroshima University Mitsuyo Saito Graduate School of Advanced Science and Engineering, Hiroshima University Toshitsugu Moroizumi Graduate School of Environmental and Life Science, Okayama University 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. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1613-6810 2025 Atomic-Level Insights into Thermal Carbonization of Ethynyl-Containing Boron Compounds e13537 EN Kentaro Ohkura Research Institute for Interdisciplinary Science, Okayama University Satoshi Hayakawa Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Naoki Takahashi Graduate School of Environment Life Natural Science and Technology, Okayama University Ken Yamazaki Graduate School of Environment Life Natural Science and Technology, Okayama University Jun Kano Graduate School of Environment Life Natural Science and Technology, Okayama University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University This study reports the design, synthesis, and characterization of boron-doped carbon (BDC) derived from a triethynylborane-pyridine complex. Triethynylborane is stabilized by coordination with pyridine, facilitating its synthesis and handling in ambient conditions. The complex is subjected to thermal treatment at various temperatures to form BDC. Powder XRD and single-crystal XRD analyses reveal that BDC prepared at 200 °C retains an ordered structure, while higher temperatures induce alkyne structural changes without significant weight or surface area alterations. Coin cells are assembled using BDC as the anode, demonstrating unique Li-ion and Na-ion storage properties distinct from graphite. These results suggest that the BDC reflects the precursor's crystal structure, enabling novel electrochemical behavior. These findings offer insight into the development of advanced BDC materials for energy storage applications. No potential conflict of interest relevant to this article was reported.

IEEE Acta Medica Okayama 2158-4001 2025 A Linear Search Algorithm for Resource Allocation in Frequency Domain Non-Orthogonal Multiple Access EN Satoshi Denno Faculty of Environmental, Life, Natural Science and Technology, Okayama University Yuto Ohba Faculty of Environmental, Life, Natural Science and Technology, Okayama University Yafei Hou Faculty of Environmental, Life, Natural Science and Technology, Okayama University This paper proposes a linear search algorithm for resource allocation in frequency domain non-orthogonal multiple access based on the low-density signature (LDS). Although the proposed linear search enables the non-orthogonal multiple access to achieve superior transmission performance, the proposed linear search makes the resource allocation implemented with lower and fixed computational complexity. The performance of the non-orthogonal access based on the proposed linear search is evaluated by computer simulation. The proposed linear search algorithm makes the non-orthogonal multiple access achieve a gain of about 6 dB at the BER of 10–5 when the overloading ratio is set to 2. The complexity of the non-orthogonal access based on the proposed linear search algorithm is approximately half as much as that of the conventional low complexity resource allocation when the overloading ratio is 2, if the complexity is evaluated in terms of the number of additions. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 2766-0400 5 1 2025 Linking structure and process in dendritic growth using persistent homology with energy analysis 2475735 EN Misato Tone Department of Material Science and Technology, Tokyo University of Science Shunsuke Sato Department of Material Science and Technology, Tokyo University of Science Sotaro Kunii Department of Material Science and Technology, Tokyo University of Science Ippei Obayashi Center for Artificial Intelligence and Mathematical Data Science, Okayama University Yasuaki Hiraoka Kyoto University Institute for Advanced Study, Kyoto University Yui Ogawa NTT Basic Research Laboratories, NTT Corporation Hirokazu Fukidome Research Institute of Electrical Communication, Tohoku University Alexandre Lira Foggiatto Department of Material Science and Technology, Tokyo University of Science Chiharu Mitsumata Department of Material Science and Technology, Tokyo University of Science Ryunosuke Nagaoka Department of Material Science and Technology, Tokyo University of Science Arpita Varadwaj Department of Material Science and Technology, Tokyo University of Science Iwao Matsuda Institute for Solid State Physics, The University of Tokyo Masato Kotsugi Department of Material Science and Technology, Tokyo University of Science We present a material analysis method that links structure and process in dendritic growth using explainable machine learning approaches. We employed persistent homology (PH) to quantitatively characterize the morphology of dendritic microstructures. By using interpretable machine learning with energy analysis, we established a robust relationship between structural features and Gibbs free energy. Through a detailed analysis of how Gibbs free energy evolves with morphological changes in dendrites, we uncovered specific conditions that influence the branching of dendritic structures. Moreover, energy gradient analysis based on morphological feature provides a deeper understanding of the branching mechanisms and offers a pathway to optimize thin-film growth processes. Integrating topology and free energy enables the optimization of a range of materials from fundamental research to practical applications. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1616-301X 2025 A Biologically-Architected Wear and Damage-Resistant Nanoparticle Coating From the Radular Teeth of Cryptochiton stelleri e21664 EN Taifeng Wang Department of Materials Science and Engineering, University of California Yu Chen Lyles School of Civil and Construction Engineering, Purdue University Ezra Sarmiento Department of Materials Science and Engineering, University of California Taige Hao Materials and Manufacturing Technologies Program, University of California Atsushi Arakaki Division of Biotechnology and Life Science, Institute of Engineering, Tokyo University of Agriculture and Technology Michiko Nemoto Graduate School of Environmental and Life Science, Okayama University Pablo Zavattieri Lyles School of Civil and Construction Engineering, Purdue University David Kisailus Department of Materials Science and Engineering, University of California 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. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 20 8 2025 Risk stratification for the prediction of skeletal-related events in patients with castration-resistant prostate cancer with bone metastases e0328792 EN Masanori Hamada Eiji Nakata Ryuichi Nakahara Shinsuke Sugihara Haruyoshi Katayama Takuto Itano Tomohiro Inoue Shota Takihira Yoshiteru Akezaki Toshifumi Ozaki 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. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1478-6362 27 1 2025 Does perioperative discontinuation of anti-rheumatic drugs increase postoperative complications in orthopedic surgery for rheumatoid arthritis? 219 EN Hiromu Ito Department of Orthopaedic Surgery, Kurashiki Central Hospital Hajime Ishikawa Department of Rheumatology, Niigata Rheumatic Center Shigeyoshi Tsuji Department of Orthopaedic Surgery, Osaka Minami Medical Center Masanori Nakayama Department of Orthopaedic Surgery, International University of Health and Welfare Keiichiro Nishida Locomotive Pain Center, Okayama University Hospital Takeshi Mochizuki Department of Orthopaedic Surgery, Kamagaya General Hospital Kosuke Ebina Department of Orthopaedic Surgery, Osaka University Faculty of Medicine Graduate School of Medicine Toshihisa Kojima Department of Orthopaedic Surgery, Nagoya University Hospital Takumi Matsumoto Department of Orthopaedic Surgery, University of Tokyo Ayako Kubota Department of Orthopaedic Surgery, Toho University Omori Medical Center Arata Nakajima Department of Orthopaedic Surgery and Rehabilitation, Toho University Sakura Medical Center Atsushi Kaneko Department of Orthopaedic Surgery, Nagoya Medical Center Isao Matsushita Department of Rehabilitation Medicine, Kanazawa Medical University Ryota Hara The Center for Rheumatic Diseases, Nara Medical University Koji Sakuraba Department of Orthopaedic Surgery, Kyushu Medical Center Yukio Akasaki Department of Orthopaedic Surgery, Kyushu University Tsukasa Matsubara Department of Orthopaedic Surgery, Matsubara Mayflower Hospital Yuichi Mochida Department of Orthopaedic Surgery, Yokohama City University Medical Center Katsuaki Kanbe Department of Orthopaedic Surgery, Nippori Orthopaedics and Rheumatic Clinic Natsuko Nakagawa Department of Orthopaedic Surgery, Kakogawa Medical Center Koichi Murata Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine Shigeki Momohara Endowed Course for Advanced Therapy for Musculoskeletal Disorders, Keio University School of Medicine Objective This study aimed to investigate whether discontinuation of biological or targeted synthetic antirheumatic disease-modifying drugs (bDMARDs or tsDMARDs) influences the incidence of postoperative complications in patients with rheumatoid arthritis (RA) undergoing orthopedic surgery.<br> Methods A retrospective multicenter cohort study including patients receiving bDMARDs or tsDMARDs who underwent orthopedic surgery was conducted. Data collected encompassed the duration of drug discontinuation and postoperative adverse events, such as delayed wound healing, surgical site infection (SSI), disease flare-ups, and mortality. The association between drug discontinuation and these outcomes was analyzed. Multivariate analyses were conducted to identify potential risk factors for these events.<br> Results A total of 2,060 cases were initially enrolled. After applying inclusion and exclusion criteria, data from 1,953 patients were analyzed. No significant differences were observed between the groups regarding delayed wound healing, SSI, or mortality. However, the incidence of disease flare-ups was substantially higher in the drug discontinuation group and in the interleukin (IL)-6 inhibitor group. Multivariate analysis identified that tumor necrosis factor α and IL-6 inhibitor use was associated with a higher risk of delayed wound healing relative to T-cell function modifiers.<br> Conclusion In orthopedic surgery for patients with RA, maintaining the standard or the half of administration interval of bDMARD appears safe in the preoperative period. However, the drug discontinuation may increase the risk of postoperative flare-ups, particularly with IL-6 inhibitors. In addition, T-cell function modifiers may be associated with a lower risk of delayed wound healing, suggesting their safety profile in this context. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1465-3621 55 4 2025 Current management of neurotrophic receptor tyrosine kinase fusion-positive sarcoma: an updated review 313 326 EN Yuta Kubota Department of Orthopaedic Surgery, Faculty of Medicine, Oita University Masanori Kawano Department of Orthopaedic Surgery, Faculty of Medicine, Oita University Tatsuya Iwasaki Department of Orthopaedic Surgery, Faculty of Medicine, Oita University Ichiro Itonaga Department of Orthopaedic Surgery, Faculty of Medicine, Oita University Nobuhiro Kaku Department of Orthopaedic Surgery, Faculty of Medicine, Oita University Toshifumi Ozaki Department of Orthopaedic Surgery , Science of Functional Recovery and Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Tanaka Department of Orthopaedic Surgery, Faculty of Medicine, Oita University In recent years, pembrolizumab has demonstrated significant efficacy in treating tumors characterized by a high tumor mutational burden and high microsatellite instability. Tropomyosin receptor kinase (TRK) inhibitors have shown considerable efficacy against tumors harboring neurotrophic receptor tyrosine kinase (NTRK) fusion genes, highlighting the growing importance of personalized medicine in cancer treatment. Advanced sequencing technologies enable the rapid analysis of numerous genetic abnormalities in tumors, facilitating the identification of patients with positive biomarkers. These advances have increased the likelihood of providing effective, tailored treatments. NTRK fusion genes are present in various cancer types, including sarcomas, and the TRK inhibitors larotrectinib and entrectinib have been effectively used for these malignancies. Consequently, the treatment outcomes for NTRK fusion-positive tumors have improved significantly, reflecting a shift toward more personalized therapeutic approaches. This review focuses on NTRK fusion-positive sarcomas and comprehensively evaluates their epidemiology, clinical features, and radiological and histological characteristics. We also investigated the treatment landscape, including the latest methodologies involving TRK inhibitors, and discussed the long-term efficacy of these inhibitors, and their optimal order of use. Notably, larotrectinib has demonstrated a high response rate in infantile fibrosarcoma, and its efficacy has been confirmed even in advanced cases. However, further research is warranted to optimize treatment duration and subsequent management strategies. The accumulation of clinical cases worldwide will play a pivotal role in refining the treatment approaches for tumors associated with NTRK fusion genes. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1467-7881 26 11 2025 Missing the Target: A Scoping Review of the Use of Percent Weight Loss for Obesity Management e13960 EN Diana Sherifali McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University Megan Racey McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University Donna Fitzpatrick‐Lewis McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University Michelle Greenway McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University Sanjeev Sockalingam Obesity Canada Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Soo Huat Teoh Department of Clinical Medicine, Advanced Medical and Dental Institute, Universiti Sains Malaysia Ian Patton Obesity Canada David Macklin Temerty Faculty of Medicine, University of Toronto Elizabeth F. C. van Rossum Department of Internal Medicine, Division of Endocrinology, and Obesity Center CGG, Erasmus MC, University Medical Center Rotterdam Luca Busetto Department of Medicine, University of Padova Deborah Bade Horn Center of Obesity Medicine and Metabolic Performance, Department of Surgery, University of Texas McGovern Medical School J. D. Patricia Nece Obesity Action Coalition Morgan Emile Gabriel Salmon Leguede ABHispalis Spain, Alianza Hispana de Personas con Obesidad Latin America Nicole Pearce Obesity Canada Carel Le Roux School of Medicine, University College Dublin Jamy Ard School of Medicine, Wake Forest University Angela S. Alberga Department of Health, Kinesiology, and Applied Physiology, Concordia University Lee Kaplan Obesity, Metabolism and Nutrition Institute Massachusetts General Hospital and Harvard Medical School Arya M. Sharma Department of Medicine, University of Alberta Sean Wharton Temerty Faculty of Medicine, University of Toronto 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.<br> 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.<br> 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.<br> 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. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2040-1116 16 6 2025 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) 1100 1111 EN Seiji Nishikage Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Yushi Hirota Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Yasushi Nakagawa Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Masamichi Ishii Center for Medical Informatics Intelligence, National Center for Global Health and Medicine Mitsuru Ohsugi Diabetes and Metabolism Information Center, Research Institute, National Center for Global Health and Medicine Eiichi Maeda Division of Medical Informatics, Department of Internal Medicine, Kobe University Graduate School of Medicine Kai Yoshimura Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Akane Yamamoto Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Tomofumi Takayoshi Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Takehiro Kato Department of Diabetes, Endocrinology, and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine Daisuke Yabe Department of Diabetes, Endocrinology, and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine Munehide Matsuhisa Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University Jun Eguchi Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yukihiro Fujita Department of Medicine, Shiga University of Medical Science Shinji Kume Department of Medicine, Shiga University of Medical Science Hiroshi Maegawa Department of Medicine, Shiga University of Medical Science Kana Miyake Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine Nobuhiro Shojima Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine Toshimasa Yamauchi Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine Koutaro Yokote Chiba University Kohjiro Ueki Diabetes Research Center, Research Institute, National Center for Global Health and Medicine Kengo Miyo Center for Medical Informatics Intelligence, National Center for Global Health and Medicine Wataru Ogawa Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine 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).<br> 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.<br> 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.<br> 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. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 10 2025 Bladder Trigone as a Sensory Hub: A Narrative Review e94951 EN Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Maruyama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Mitsui Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takanori Sekito Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomofumi Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The bladder trigone is an anatomically and functionally distinct region within the lower urinary tract (LUT), characterized by a dense network of afferent sensory fibers, specialized urothelial interactions, and prominent mechanotransduction mechanisms. Its intricate neuroarchitecture enables precise detection of bladder filling and coordination of micturition, whereas dysregulation of these pathways contributes to lower urinary tract symptoms (LUTS), including urgency, frequency, and bladder pain. Despite its recognized clinical relevance, the structural and functional basis of trigonal sensory signaling - and its role - remain incompletely understood.<br> This review synthesizes current evidence on trigonal afferent organization, integrating data from anatomical mapping, receptor profiling, electrophysiological characterization, and translational research. Seminal anatomical observations are combined with recent advances in mechanotransduction and purinergic, peptidergic, and transient receptor potential (TRP) signaling to provide a comprehensive perspective. The trigone exhibits three principal afferent classes: (1) intraepithelial fibers penetrating umbrella cells, marked by P2X purinoceptor 3 (P2X3), transient receptor potential vanilloid 1 (TRPV1), calcitonin gene-related peptide (CGRP), and substance P (SP); (2) subepithelial plexuses surrounding microvasculature, enriched in vasoactive neuropeptides and exhibiting plastic hypertrophy in overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS); and (3) encapsulated corpuscular endings at the lamina propria-detrusor junction, expressing PIEZO1/2 and acid-sensing ion channels (ASICs) for rapid adaptation. In trigeminal dorsal root ganglion (DRG) neurons, high expression of PIEZO2, P2RX3, and voltage-gated sodium channel, type 1.8 (Nav1.8) was observed, revealing their role as the foundation for multisensory information processing. Functional assays highlight distinct mechanotransductive and chemosensory pathways, with aging, inflammation, and neurotrophic factors driving afferent plasticity underlying abnormal bladder sensation, such as urgency, frequency, and pain. Early clinical trials of P2X3 antagonists and intravesical TRPV1 inhibitors demonstrate promising symptomatic benefits. Collectively, evidence positions the bladder trigone as a critical sensory hub where neuronal, urothelial, and immune signals converge to regulate bladder sensation. Understanding its molecular and structural specialization may inform the development of region-specific neuromodulatory therapies targeting sensory urgency and afferent-driven bladder dysfunction. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0006-291X 786 2025 Hydrogen-rich gas enhances mitochondrial membrane potential and respiratory function recovery in Caco-2 cells post-ischemia-reperfusion injury 152753 EN Mizuki Seya Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Aokage Biological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology Ying Meng Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Hirayama Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takafumi Obara Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tsuyoshi Nojima Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosaki Yoshinori Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Yumoto Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Watanabe Department of Emergency, Disaster and Critical Care Medicine, Hyogo Medical University Taihei Yamada Department of Emergency, Disaster and Critical Care Medicine, Hyogo Medical University Hiromichi Naito Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsunori Nakao Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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.<br> 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.<br> 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.<br> 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. No potential conflict of interest relevant to this article was reported.

Ivyspring International Publisher Acta Medica Okayama 1837-9664 16 14 2025 CXCR4 Inhibition Induces Tumor Necrosis by Selectively Targeting the Proliferating Blood Vessels in Oral Squamous Cell Carcinoma 4055 4070 EN Yamin Soe Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Htoo Shwe Eain Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Saori Yoshida Preliminary Examination Room, Okayama University Hospital May Wathone Oo Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Zin Zin Min Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Kiyofumi Takabatake Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University 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. No potential conflict of interest relevant to this article was reported.

American Society of Hematology Acta Medica Okayama 2473-9529 9 18 2025 Refinement of day 28 treatment response criteria for acute GVHD: a collaboration study of the JSTCT and MAGIC 4640 4653 EN Yu Akahoshi Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Yoshihiro Inamoto Department of Blood and Marrow Transplantation and Cellular Therapy, Fujita Health University School of Medicine Nikolaos Spyrou Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Hideki Nakasone Division of Hematology, Jichi Medical University Saitama Medical Center Marcio A. Diniz Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Francis Ayuk Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf Hannah K. Choe Division of Hematology, Blood and Marrow Transplantation Program, The Ohio State University Comprehensive Cancer Center Noriko Doki Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Tetsuya Eto Department of Hematology, Hamanomachi Hospital Aaron M. Etra Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Elizabeth O. Hexner Department of Medicine and Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania Nobuhiro Hiramoto Department of Hematology, Kobe City Medical Center General Hospital William J. Hogan Division of Hematology, Mayo Clinic Ernst Holler Department of Hematology and Oncology, Internal Medicine III, University of Regensburg Keisuke Kataoka Division of Molecular Oncology, National Cancer Center Research Institute Toshiro Kawakita Department of Hematology, National Hospital Organization Kumamoto Medical Center Masatsugu Tanaka Department of Hematology, Kanagawa Cancer Center Takashi Tanaka Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital Naoyuki Uchida Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital Ingrid Vasova Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg and University Hospital Erlangen Satoshi Yoshihara Department of Hematology, Hyogo Medical University Hospital Fumihiko Ishimaru Technical Department, Japanese Red Cross Blood Service Headquarters Takahiro Fukuda Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital Yi-Bin Chen Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital Junya Kanda Department of Hematology, Graduate School of Medicine, Kyoto University Ryotaro Nakamura Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation James L. M. Ferrara Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Yoshinobu Kanda Division of Hematology, Jichi Medical University Saitama Medical Center John E. Levine Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Takanori Teshima Department of Hematology, Hokkaido University Faculty of Medicine and Graduate School of Medicine Overall response (OR) that combines complete (CR) and partial responses (PR) is the conventional end point for acute graft-versus-host disease (GVHD) trials. Because PR includes heterogeneous clinical presentations, reclassifying PR could produce a better end point. Patients in the primary treatment cohort from the Japanese Society for Transplantation and Cellular Therapy (JSTCT) were randomly divided into training and validation sets. In the training set, a classification and regression tree algorithm generated day 28 refined response (RR) criteria based on symptoms at treatment and day 28. We then evaluated RR for primary and second-line treatments, using the area under the receiver operating characteristic curve (AUC) and negative predictive value (NPV) for 6-month nonrelapse mortality as performance measures. RR considered patients with grade 0/1 at day 28 without additional treatment as responders. RR for primary treatment produced higher AUCs than OR with small improvement of NPVs in both validation sets: JSTCT (AUC, 0.73 vs 0.69 [P < .001]; NPV, 92.0% vs 89.6% [P < .001]) and the Mount Sinai Acute GVHD International Consortium (MAGIC; AUC, 0.71 vs 0.68 [P = .032]; NPV, 90.9% vs 89.8% [P = .009]). RR for second-line treatment produced similar AUCs but much higher NPVs than OR in both validation sets of JSTCT (AUC, 0.64 vs 0.63 [P = .775]; NPV, 74.5% vs 66.0% [P < .001]) and MAGIC (AUC, 0.67 vs 0.64 [P = .105]; NPV, 86.8% vs 76.1% [P = .004]). Classifying persistent but mild skin symptoms as responses and residual lower gastrointestinal GVHD as nonresponses were major drivers in improving the prognostic performance of RR. Our externally validated day 28 RR would serve as a better end point than conventional criteria in future first- and second-line treatment trials. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0007-1048 2025 Efficacy of ciclosporin monotherapy in non-severe aplastic anaemia not requiring transfusions: Results from a multicentre phase II study EN Ken Ishiyama Department of Hematology, Kanazawa University Hospital Masahide Yamazaki Department of Internal Medicine, Keiju Medical Center Hiroyuki Maruyama Department of Hematology, Kanazawa University Hospital Naoko Hosono Department of Hematology and Oncology, University of Fukui Hospital Hiroki Yamaguchi Department of Hematology, Nippon Medical School Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Kazuki Tanimoto Department of Hematology and Oncology, Japanese Red Cross Fukuoka Hospital Hiroyuki Sugiura Department of Hematology, Chugoku Central Hospital of Japan Mutual Aid Association of Public School Teachers Kensuke Usuki Department of Hematology, NTT Medical Center Tokyo Kenichi Yoshimura Department of Biostatistics and Health Data Science, Graduate School of Medical Science, Nagoya City University Seishi Ogawa Department of Pathology and Tumor Biology, Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University Yuzuru Kanakura Sumitomo Hospital Itaru Matsumura Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Koichi Akashi Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences Shinji Nakao Department of Hematology, Kanazawa University Hospital The efficacy of ciclosporin (CsA) to treat transfusion-independent non-severe aplastic anaemia (TI-NSAA) has not yet been systematically evaluated. We conducted a prospective trial in patients with TI-NSAA treated with CsA monotherapy. CsA (3.5 mg/kg/day) was administered to patients with TI-NSAA aged ≥16. The CsA dose was adjusted to maintain a blood CsA level of ≥600 ng/mL at 2 h post-administration. Blood cell counts were assessed after 8, 16 and 52 weeks of therapy. Thirty-two evaluable patients from 21 institutions were enrolled. The median age was 63.5 (range: 16–83) years. At 8 weeks, haematological improvement, with increases in haemoglobin (Hb) ≥1.5 g/dL (haematological improvement in erythrocytes [HI-E]) and platelet count ≥30 × 109/L (haematological improvement in platelets [HI-P]), was observed in 0/25 (0%) and 6/32 (19%) evaluable cases respectively. HI-E and HI-P occurred in 1/25 (4%) and 10/32 (31%) patients at 16 weeks, respectively, and at 52 weeks in 5/25 (20%) and 16/32 (50%) patients respectively. Nine grade 3 adverse events (AEs) occurred in six patients, but there were no grade ≥4 AEs. Ten of the 32 patients experienced grade 2 renal toxicity. Low-dose CsA is effective in TI-NSAA patients and demonstrates minimal renal toxicity. However, at least 16 weeks are necessary to adequately evaluate its efficacy. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 2025 Japanese society for cancer of the colon and rectum (JSCCR) guidelines 2024 for the clinical practice of hereditary colorectal cancer EN Kohji Tanakaya Department of Surgery, National Hospital Organization Iwakuni Clinical Center Tatsuro Yamaguchi Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Keiji Hirata Department of Surgery 1, University of Occupational and Environmental Health Masayoshi Yamada Endoscopy Division, National Cancer Center Hospital Kensuke Kumamoto Department of Genome Medical Science and Medical Genetics, Faculty of Medicine, Kagawa University Yasuki Akiyama Department of Surgery 1, University of Occupational and Environmental Health Kei Ishimaru Division of Gastrointestinal Surgery and Surgical Oncology, Graduate School of Medicine, Ehime University Koichi Okamoto Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science Yuko Kawasaki College of Nursing, University of Hyogo Keigo Komine Department of Medical Oncology, Tohoku University Hospital Akira Sakamoto Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshiko Shibata Himawari-No-Kai (Sunflower Association), a Patient Advocacy Group for Individuals and Families Affected By Lynch Syndrome Yusaku Shimamoto Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine Hideki Shimodaira Division of Medical Oncology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University Shigeki Sekine Department of Pathology, Keio University School of Medicine Akinari Takao Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Misato Takao Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Yasuyuki Takamizawa Department of Colorectal Surgery, National Cancer Center Hospital Yoji Takeuchi Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine Noriko Tanabe Department of Clinical Genetics, Saitama Medical Center, Saitama Medical University Fumitaka Taniguchi Department of Surgery, Hiroshima City Hospital Organization Hiroshima City Hiroshima Citizens Hospital Akiko Chino Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research Hourin Cho Endoscopy Center, Tokyo Medical University Hospital Satoru Doi Harmony Line (Association for Patients and Families With Familial Adenomatous Polyposis) Takeshi Nakajima Division of Hereditary Tumors, Department of Genetic Oncology, Osaka International Cancer Institute Sakiko Nakamori Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Yoshiko Nakayama Department of Pediatrics, Shinshu University School of Medicine Toshiya Nagasaki Department of Gastroenterological Surgery, Saitama Cancer Center Hisashi Hasumi Department of Urology, Yokohama City University Kouji Banno Center of Maternal -Fetal/Neonatal Medicine, Hiroshima University Hospital Takao Hinoi Department of Clinical and Molecular Genetics, Hiroshima University Hospital Kenji Fujiyoshi Department of Surgery, Kurume University School of Medicine Takahiro Horimatsu Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital Kenta Masuda Department of Obstetrics and Gynecology, Keio University School of Medicine Masashi Miguchi Department of Gastroenterological Surgery, Hiroshima Prefectural Hospital Yusuke Mizuuchi Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University Yasuyuki Miyakura Department of Colon and Pelvic Surgery, Cancer Prevention and Genetic Counseling, Tochigi Cancer Center Michihiro Mutoh Department of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Takahiro Yoshioka Department of Gastroenterological Surgery, Kochi Health Sciences Center Shinji Tanaka JA Onomichi General Hospital Kazuhiro Sakamoto Koshigaya Municipal Hospital Kentaro Sakamaki Faculty of Health Data Science, Juntendo University Michio Itabashi Saiseikai Kazo Hospital Hideyuki Ishida Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University Naohiro Tomita Division of Cancer Treatment , Toyonaka Municipal Hospital Kenichi Sugihara Institute of Science Tokyo Yoichi Ajioka Division of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata University Approximately 5% of all colorectal cancers have a strong genetic component and are classified as hereditary colorectal cancer (HCRC). Some of the unique features commonly seen in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics require different management approaches, including diagnosis, treatment or surveillance, from those used in the management of sporadic colorectal cancer. Accurate diagnosis of HCRC is essential because it enables targeted surveillance and risk reduction strategies that improve patient outcomes. Recent genetic advances revealed several causative genes for polyposis and non-polyposis syndromes. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) first published guidelines for the management of HCRC in 2012, with subsequent revisions every 4 years. The 2024 update to the JSCCR guidelines for HCRC was developed by meticulously reviewing evidence from systematic reviews and the consensus of the JSCCR HCRC Guidelines Committee, which includes representatives from patient advocacy groups for FAP and Lynch syndrome. These guidelines provide an up-to-date summary of HCRC, along with clinical recommendations for managing FAP and Lynch syndrome. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1436-3291 28 6 2025 Gallbladder edema as a clue to zolbetuximab-associated protein-losing enteropathy in gastric cancer: a case report 1297 1301 EN Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shinji Kuroda Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunya Hanzawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Nobuhiko Kanaya Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hajime Kashima Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Satoru Kikuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yoshiyasu Kono Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunsuke Kagawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine We report a rare case of protein-losing enteropathy (PLE) during zolbetuximab treatment in a 73-year-old woman with Stage IVB gastric cancer. After chemo-immunotherapy and curative surgery, 3rd-line treatment with capecitabine, oxaliplatin, and zolbetuximab was initiated due to recurrence. The patient developed persistent right upper abdominal pain; imaging revealed gallbladder wall edema, followed by mild gastric wall edema, despite unremarkable laboratory findings. Protein-losing scintigraphy demonstrated abnormal gastric protein leakage, leading to a diagnosis of PLE. While gastrointestinal toxicity is known with zolbetuximab, this is, to our knowledge, the first clinically diagnosed case of PLE in which gallbladder edema served as a diagnostic clue. As treatment strategies for advanced gastric cancer grow increasingly complex, achieving maximum therapeutic benefit requires not only optimal drug selection but also timely recognition and management of adverse events. With the broader use of zolbetuximab, clinicians should be mindful of this rare but potentially significant complication. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-230X 25 1 2025 Neoadjuvant chemotherapy strategies for optimizing safety and efficacy in elderly patients with locally advanced gastric cancer 670 EN Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shinji Kuroda Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunya Hanzawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Nobuhiko Kanaya Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hajime Kashima Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Satoru Kikuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunsuke Kagawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Background The completion rate of adjuvant chemotherapy for gastric cancer (GC) is suboptimal, particularly in elderly patients. While neoadjuvant chemotherapy (NAC) for locally advanced GC has shown promise, data on elderly patients remain limited. Given the considerable physical burden of NAC, optimizing its administration is crucial. This study evaluates the safety and efficacy of a modified approach for elderly patients.<br> Methods A retrospective analysis was conducted on 38 patients with cStage II/III GC who received NAC between November 2015 and December 2023. Additionally, 25 patients aged ≥ 75 years with cStage III who underwent upfront surgery during the same period were analyzed.<br> Results The NAC group was divided into non-elderly (< 75 years, n = 27) and elderly (≥ 75 years, n = 11) groups. The elderly group had poorer ECOG-PS (p = 0.016). While all non-elderly patients completed ≤ 3 cycles, more elderly patients underwent 4 cycles (p = 0.0047). However, per-cycles of S-1 (p = 0.0003) and oxaliplatin (p = 0.0018) were lower in the elderly group. Importantly, adverse events and treatment efficacy were comparable between groups. Among patients aged ≥ 75 years, the upfront surgery group had poorer ECOG-PS (p = 0.017) and underwent more frequent distal gastrectomy (p = 0.014).<br> Conclusions NAC can be safely administered to elderly patients by increasing cycles while reducing per-cycle dosage. It may also serve as a viable alternative to upfront surgery. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2025 Comparative Analysis of a Dual DNA–RNA Panel and a DNA-Only Panel for Sarcoma: Real-World Data From a Nationwide Genomic Database EN Eiji Nakata Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tatsunori Osone Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyuki Kunisada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mashu Futagawa Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akira Hirasawa Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinichi Toyooka Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 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. No potential conflict of interest relevant to this article was reported.

岡山大学経済学会 Acta Medica Okayama 2433-4146 57 2 2025 The Evolution and Challenges of Consumer Behavior Models in the Age of AI Co-Existence 49 80 EN Sawut Shazadigul Faculty of Humanities and Social Sciences, Okayama University 10.18926/OER/69553 　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.<br> 　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.<br> 　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. No potential conflict of interest relevant to this article was reported.

Microbiology Society Acta Medica Okayama 0022-1317 106 7 2025 Virus taxonomy proposal summaries: a searchable and citable resource to disseminate virus taxonomy advances 002079 EN Richard Mayne Nuffield Department of Medicine, University of Oxford Peter Simmonds Nuffield Department of Medicine, University of Oxford Donald B. Smith Nuffield Department of Medicine, University of Oxford Evelien M. Adriaenssens Quadram Institute Bioscience Elliot J. Lefkowitz Department of Microbiology, University of Alabama at Birmingham Hanna M. Oksanen Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki Francisco Murilo Zerbini Departamento de Fitopatologia/BIOAGRO, Universidade Federal de Viçosa Poliane Alfenas-Zerbini Departamento de Microbiologia, Universidade Federal de Viçosa Frank O Aylward Department of Biological Sciences, Virginia Tech Juliana Freitas-Astúa Embrapa Cassava and Fruits, Cruz das Almas R. Curtis Hendrickson Department of Microbiology, University of Alabama at Birmingham Holly R. Hughes Centers for Disease Control and Prevention Mart Krupovic Institut Pasteur, Université Paris Cité, CNRS UMR6047, Archaeal Virology Unit Jens H. Kuhn Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health Małgorzata Łobocka Institute of Biochemistry and Biophysics of the Polish Academy of Sciences Arcady R. Mushegian Division of Molecular and Cellular Biosciences, National Science Foundation Judit Penzes Institute for Quantitative Biomedicine, Rutgers University Alejandro Reyes Muñoz Departamento de Ciencias Biológicas, Universidad de los Andes David L. Robertson MRC-University of Glasgow Centre for Virus Research Simon Roux Department of Energy, Joint Genome Institute, Lawrence Berkeley National Laboratory Luisa Rubino Consiglio Nazionale delle Ricerche, Istituto per la Protezione Sostenibile delle Piante, Sede Secondaria di Bari Sead Sabanadzovic Department of Agricultural Science and Plant Protection, Mississippi State University Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University Dann Turner Molecular Biology, University of the West of England Koenraad Van Doorslaer Department of Immunobiology, School of Animal and Comparative Biomedical Sciences, BIO5 Institute, University of Arizona Cancer Center Arvind Varsani The Biodesign Center for Fundamental and Applied Microbiomics, School of Life Sciences, Center for Evolution and Medicine, Arizona State University Taxonomic classification of cellular organisms requires the publication of descriptions and proposed names of species and the deposition of specimens. Virus taxonomy is developed through a different system of annual submission of formal taxonomy proposals (TPs) that can be submitted by anyone but are typically prepared by a study group appointed by the International Committee on Taxonomy of Viruses (ICTV) and consisting of experts on a particular group of viruses. These are initially evaluated by an expert subcommittee and by the executive committee (EC) of the ICTV. EC-approved TPs are then submitted for evaluation and a ratification vote by the wider ICTV membership. Following ratification, the new taxonomy is annually updated in the Master Species List, associated databases and bioinformatic resources. The process is consistent, creates traceability in assignments and supports a fully evaluated, hierarchical classification and nomenclature of all taxonomic ranks from species to realms. The structure also facilitates large-scale and coordinated changes to virus taxonomy, such as the recent introduction of a binomial species nomenclature.<br> TPs are available on the ICTV website after ratification, but they are not indexed in bibliographic databases and are not easily cited. Authors of TPs do not receive citation credit for adopted proposals, and their voluntary contributions are largely invisible in the published literature. For greater visibility of TPs and their authors, the ICTV will commence the annual publication of summaries of all TPs from each ICTV subcommittee. These summaries will provide a searchable compendium of all annual taxonomy changes and additions as well as direct links to the Master Species List and other ICTV bioinformatic resources. Their publication will provide due credit and citations for their authors, form the basis for disseminating taxonomy decisions and promote greater visibility and accessibility to taxonomy changes for the virology community. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2198-3844 2025 A Viral RNA Silencing Suppressor Modulates Reactive Oxygen Species Levels to Induce the Autophagic Degradation of Dicer‐Like and Argonaute‐Like Proteins e06572 EN Shiyu Zhai State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University Tianxing Pang State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University Shiyu Peng State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University Shenshen Zou Department of Plant Pathology, College of Plant Protection, Shandong Agricultural University Zhiping Deng Institute of Virology and Biotechnology, Zhejiang Academy of Agricultural Sciences Nobuhiro Suzuki Institute of Plant Science and Resources (IPSR), Okayama University Zhensheng Kang State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University Ida Bagus Andika State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University Liying Sun State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University 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. No potential conflict of interest relevant to this article was reported.

Copernicus GmbH Acta Medica Okayama 2194-9034 XLVIII-4/W9-2024 2024 3D MONITORING OF COASTAL EROSION CONTROL STRUCTURES USING UAV 313 320 EN N. Sakamoto Graduate School of Environmental and Life Science, Okayama University S. Nishiyama Graduate School of Environmental and Life Science, Okayama University Coastal erosion has increasingly become a problem in recent years due to rising sea levels caused by global warming. To prevent further coastal erosion and damage, control structures like seawalls and breakwaters have been installed along vulnerable coastlines. However, it is crucial that these structures are regularly and thoroughly inspected for any abnormalities or deformations. At present, inspections are done manually by visual surveys which are time-consuming and inefficient. There is great potential to optimize this process using drone technology equipped with 3D laser scanners. In this study, we utilized a drone with a green laser scanner to inspect and diagnose control structures along the coast. We conducted surveys to determine the basic performance of this approach and used ICP algorithms to extract any deformations in vanishing wave blocks over two time periods. Our results showed high variability in basic performance due to the influence of waves during the surveys. However, we were still able to detect strain of around 50 cm in a submerged breakwater located 3 meters below the water's surface. Furthermore, an overall settlement of approximately 34 cm was observed in the vanishing wave blocks along with some localized movements. This demonstrates that drones can be successfully implemented for efficient inspection, diagnosis and detection of abnormalities and deformations in coastal structures that are extremely difficult to identify through visual surveys alone. The use of this advanced technology will allow for quicker identification of at-risk structures, enabling timely maintenance and prevention of further coastal erosion. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2075-1729 15 11 2025 Kidney Organoids: Current Advances and Applications 1680 EN Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naruhiko Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Haraguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinji Kitamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0385-2407 52 10 2025 Biologics and Small‐Molecule Therapies in Netherton Syndrome: A Comprehensive Review 1483 1493 EN Shin Morizane Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Mukai Department of Immunology and Molecular Genetics, Kawasaki Medical School Ko Sunagawa Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken‐ichi Hasui Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Anri Morita Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hayato Nomura Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mamoru Ouchida Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Netherton syndrome (NS) is a rare congenital ichthyosis caused by loss-of-function mutations in the SPINK5 gene, leading to defective expression of the serine protease inhibitor LEKTI. Dysregulated epidermal protease activity results in impaired skin barrier function and chronic inflammation, accompanied by complex immune profiles. NS patients commonly show activation of the inflammatory axis, centered on IL-17 and IL-36, in the skin and blood, and show a psoriasis-like shift to Th17. Conversely, the immune profile differs depending on the clinical type, with ichthyosis linearis circumflexa type characterized by complement activation and Th2-type allergic responses, and scaly erythroderma type characterized by a type I IFN signature and Th9-type allergic responses. While symptomatic treatments such as emollients and topical corticosteroids have been the mainstay of care, recent advances have opened new therapeutic avenues involving biologic agents and oral small-molecule immunomodulators. This review provides a comprehensive overview of the current clinical landscape and future directions of biologics (e.g., dupilumab, secukinumab, ustekinumab) and small-molecule therapies (e.g., JAK inhibitors such as tofacitinib, baricitinib, and upadacitinib) in the treatment of NS. Though evidence remains limited to case reports and small series, preliminary data suggest that cytokine-targeted interventions—particularly those inhibiting IL-4, IL-13, IL-17, IL-36, and JAK pathways—may offer tangible clinical benefits. Well-designed clinical trials and mechanistic investigations are crucial to establishing their place in NS management. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1477-0520 23 27 2025 Fluorescence detection of DNA with a single-base mismatch by a Tm-independent peptide nucleic acid (PNA) twin probe 6557 6563 EN Koki Ishii Department of Applied Chemistry, Kindai University Hajime Shigeto Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Shohei Yamamura Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Yoshitane Imai Department of Applied Chemistry, Kindai University Takashi Ohtsuki Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mizuki Kitamatsu Department of Applied Chemistry, Kindai University There is a need to develop efficient methods for detecting target nucleic acids to enable the rapid diagnosis and early treatment of diseases. We previously demonstrated that a peptide nucleic acid (PNA) twin probe, consisting of two PNAs each containing a fluorescent dye, with pyrene at one end, detects target DNA sequence-specifically through pyrene excimer emission. In this study, to advance the development of this probe system, we further investigated the fluorescence properties of the PNA twin probe P1 and P2, and found that the excimer fluorescence was significantly reduced when a mismatched base in the DNA sequence was present at the site of P1 closest to the pyrene. In other words, this probe was found to detect single-base mismatches without taking into account the thermal stability of the PNA/DNA hybrid. The detection limit of this PNA twin probe for the single-base-mismatched DNA was 2.7 nM. In the future, this probe should lead to a method to detect point mutations in endogenous nucleic acids within cells. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 17 20 2025 Tertiary Lymphoid Structures Are Associated with Favorable Clinical Outcomes and Negatively Correlated with Cancer-Associated Fibroblasts in Esophageal Cancer 3351 EN Tomoyoshi Kunitomo Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Noma Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Noriyuki Nishiwaki Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Seitaro Nishimura Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasushige Takeda Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hijiri Matsumoto Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsuya Takahashi Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kento Kawasaki Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaaki Akai Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoaki Maeda Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoru Kikuchi Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunsuke Tanabe Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Tazawa Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuhiro Shirakawa Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Esophageal cancer remains a highly aggressive malignant tumor with poor prognosis, despite advances in combination therapies and novel immunotherapies. Tertiary lymphoid structures (TLSs), characterized by densely packed CD20+ B cells in a germinal-center-like structure, have recently been recognized as immune-stimulating components within the tumor microenvironment. In contrast, cancer-associated fibroblasts (CAFs) are stromal cells expressing fibroblast-activating protein (FAP) involved in immunosuppression. Methods: In this retrospective study, 124 clinical samples from patients who underwent radical surgery for esophageal cancer at our institute were analyzed. We investigated whether TLSs could serve as a prognostic factor and examined their association with tumor microenvironment factors. Results: The presence of TLSs was an independent prognostic factor for overall and progression-free survival in multivariate analyses. A high level of TLS formation correlated with better nutritional status, fewer M2 macrophages, and greater plasma cell infiltration. Additionally, little TLS formation was observed in areas with abundant CAFs, and quantitative analyses revealed a significant negative correlation between TLSs and CAFs. Conclusions: TLSs enhance antitumor immunity via macrophages and plasma cells and can be a valuable prognostic indicator in patients undergoing surgery for esophageal cancer. Targeting CAFs may prove to be a promising therapeutic strategy to enhance tumor-immunity-related TLSs. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 1109-6535 22 6 2025 C1orf50 Accelerates Epithelial-Mesenchymal Transition and the Cell Cycle of Hepatocellular Carcinoma 836 849 EN ATSUSHI TANAKA Department of Pathology, Beth Israel Deaconess Medical Center YUSUKE OTANI Department of Pathology, Beth Israel Deaconess Medical Center MASAKI MAEKAWA Department of Pathology, Beth Israel Deaconess Medical Center ANNA ROGACHEVSKAYA Department of Pathology, Beth Israel Deaconess Medical Center TIRSO PEÑA Department of Pathology, Beth Israel Deaconess Medical Center VANESSA D. CHIN UMass Chan Medical School, UMass Memorial Medical Center SHINICHI TOYOOKA Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences MICHAEL H. ROEHRL Department of Pathology, Beth Israel Deaconess Medical Center ATSUSHI FUJIMURA Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Aim: Hepatocellular carcinoma (HCC) is a heterogeneous liver cancer with limited treatment options and a poor prognosis in advanced stages. To identify novel biomarkers and therapeutic targets, we investigated the role of chromosome 1 open reading frame 50 (C1orf50), a gene with a previously uncharacterized function in HCC.<br> Materials and Methods: We performed a comprehensive transcriptome data analysis of the human hepatocellular carcinoma project from The Cancer Genome Atlas (TCGA) and subsequently validated the oncogenic roles of C1orf50 using HCC cell lines.<br> Results: Using transcriptomic and clinical data from TCGA, we stratified 355 primary HCC samples based on C1orf50 expression levels. Patients with high C1orf50 expression exhibited significantly shorter overall survival, suggesting its association with aggressive tumor behavior. Differential expression and enrichment analyses revealed that C1orf50-high tumors were enriched in oncogenic pathways, including epithelial-mesenchymal transition (EMT), cell cycle activation, and stemness-related properties. Transcriptional regulatory network analysis detected 456 significantly dysregulated regulons, including ZEB1/2 and E2F2, key drivers of EMT and cell cycle, in the C1orf50-high group. In addition, we observed increased YAP1/TAZ signaling, further linking C1orf50 to stemness and therapeutic resistance. Functional data from CRISPR-based dependency screening suggested that several transcription factors up-regulated in the C1orf50-high state, such as ZBTB11 and CTCE, are essential for the survival of HCC cells. These findings indicate potential therapeutic vulnerabilities and support the rationale for targeting C1orf50-associated pathways.<br> Conclusion: C1orf50 is a novel biomarker of poor prognosis in HCC and a key regulator of oncogenic features such as EMT, cell cycle progression, and stemness. This study highlights the therapeutic potential of targeting C1orf50-related networks in aggressive subtypes of liver cancer. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1340-2838 32 4 2025 Reference-based chromosome-scale assembly of Japanese barley (Hordeum vulgare ssp. vulgare) cultivar Hayakiso 2 dsaf016 EN Tsuyoshi Tanaka Bioinformatics Unit, Research Center for Advanced Analysis, National Agriculture and Food Research Organization Yuhi Haraguchi Department of Crop Production and Breeding, Fukuoka Agriculture and Forestry Research Center Takatomo Todoroki Department of Crop Production and Breeding, Fukuoka Agriculture and Forestry Research Center Daisuke Saisho Barley Germplasm Center, Institute of Plant Science and Resources, Okayama University Tomomi Abiko Laboratory of Agroecology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University Hiroomi Kai Department of Crop Production and Breeding, Fukuoka Agriculture and Forestry Research Center Current advances in next-generation sequencing (NGS) technology and assembling programs permit construct chromosome-level genome assemblies in various plants. In contrast to resequencing, the genome sequences provide comprehensive annotation data useful for plant genetics and breeding. Herein, we constructed a reference-based genome assembly of winter barley (H. vulgare ssp. vulgare) cv. ‘Hayakiso 2’ using long and short read NGS data and barley reference genome sequences from ‘Morex’. We constructed ‘Hayakiso 2’ genome sequences covering 4.3 Gbp with 55,477 genes. Comparative genomics revealed that 14,106 genes had orthologs to two barley data, wheat (A, B, and D homoeologs, respectively), and rice. From the gene ontology analysis, 2,494 orthologs against wheat and rice but not two barley contained agricultural important genes, such as ‘response to biotic and abiotic stress’ and ‘metabolic process’. Phylogenetic analysis using 76 pangenome data indicated that ‘Hayakiso 2’ was clustered into Japanese-type genomes with unique alleles. ‘Hayakiso 2’ genome sequences showed known genes related to flowering and facilitated barley breeding through the development of various markers related to agronomically important alleles such as tolerance to various types of biotic and abiotic stress. Therefore, ‘Hayakiso 2’ genome sequences will be used for the further barley breeding. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0921-8831 36 10 2025 Evaluating the effects of electrolytes on the interaction forces between alumina surfaces in polyacrylic acid solutions using atomic force microscopy 105028 EN Naoto Kishimoto Graduate School of Natural Science and Technology, Okayama University Ryota Kaji Faculty of Science and Engineering, Doshisha University Katsumi Tsuchiya Faculty of Science and Engineering, Doshisha University Koreyoshi Imamura Graduate School of Natural Science and Technology, Okayama University Naoyuki Ishida Faculty of Science and Engineering, Doshisha University Evaluation and control of ceramic slurry at the microscopic level are critical to ensure consistent quality in manufactured ceramics. Notably, metal ions such as Mg2+ and Al3+ are common in ceramic slurries and significantly influence the stability of particle. This study applied atomic force microscopy to investigate the interaction forces between alumina particle surfaces in the presence of different concentrations of three metal ions and polyacrylic acid (PAA), a widely used dispersant.<br> The attractive forces observed at low PAA concentrations were attributed to polymer bridging between alumina surfaces, whereas the repulsive forces observed at high PAA concentrations were attributed to the domination of steric repulsion between adsorbed PAA molecules. The presence of multivalent metal ions, such as Mg2+ and Al3+, modulated these interactions; an increasing ion valence induced a transition from repulsive to attractive force, primarily owing to electrostatic screening, which caused conformational collapse of the PAA chains and diminished the range of steric repulsion. Similarly, increasing the concentration of these metal ions decreased the range of repulsive forces, eventually resulting in a net attraction driven by the same electrostatic and polymer conformation mechanisms. Notably, the addition of 0.1 M AlCl3 produced an anomalous long-range attraction between surfaces that could not be explained by conventional mechanisms, such as polymer bridging or electrostatic interactions between charge domains. No potential conflict of interest relevant to this article was reported.

Japanese Society for Plant Cell and Molecular Biology Acta Medica Okayama 1342-4580 42 3 2025 Root-exuded sugars as drivers of rhizosphere microbiome assembly 215 227 EN Niarsi Merry Hemelda Department of Biology, Faculty of Mathematics and Natural Sciences, University of Indonesia Yoshiteru Noutoshi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sugars in root exudates play a pivotal role in shaping plant-microbe interactions in the rhizosphere, serving as carbon sources and signaling molecules that orchestrate microbial behavior, community structure, and plant resilience. Recent research has shed light on the dynamics of sugar levels in root exudates, the factors that influence their secretion, and the mechanisms by which these sugars drive microbial colonization and community assembly in the rhizosphere. Microbial communities, in turn, contribute to plant physiological changes that enhance growth and stress tolerance. While well-studied sugars such as glucose, sucrose, and fructose are known to promote chemotaxis, motility, and biofilm formation, emerging evidence suggests that less-studied sugars like arabinose and trehalose may also play significant roles in microbial interactions and stress resilience. Key challenges remain, including the accurate measurement of labile sugars that are rapidly metabolized by microbes, and the elucidation of genetic mechanisms underlying rhizosphere metabolic interactions in both host plants and microbes. Addressing these challenges will advance our understanding of sugar-mediated interactions and inform the development of sustainable agricultural innovations. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Gastroduodenal Artery-Preserving Pancreatoduodenectomy after Esophagectomy with Gastric Conduit Reconstruction 393 398 EN Akari Masunaga Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motohiko Yamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeyoshi Nishiyama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriyuki Kanehira Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yumi Sota Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/69441 Pancreatoduodenectomy (PD) after esophagectomy with gastric conduit reconstruction is technically challenging. Preserving the blood supply of the gastric conduit is crucial in performing PD after esophagectomy. We report the case of a 66-year-old man who underwent gastroduodenal artery-preserving PD after esophagectomy with gastric conduit reconstruction for intraductal papillary mucinous neoplasm. The patient developed pseudoaneurysm rupture postoperatively, but was successfully treated with interventional radiology. Precise assessment is important in developing a surgical strategy depending on the patient’s specific anatomy and tumor characteristics. Moreover, special attention should be paid to avoid accidental injuries of the gastric conduit and gastric vessels during surgery. No potential conflict of interest relevant to this article was reported.

Institute of Electrical and Electronics Engineers (IEEE) Acta Medica Okayama 1932-4537 22 5 2025 Topology-Driven Configuration of Emulation Networks With Deterministic Templating 3933 3946 EN Satoru Kobayashi Faculty of Environmental, Life, Natural Science and Technology, Okayama University Ryusei Shiiba Department of Informatics, School of Multidisciplinary Sciences, The Graduate University of Advanced Studies, Sokendai Shinsuke Miwa StarBED Technology Center, Testbed Research, Development and Operations Laboratory, National Institute of Information and Communications Technology Toshiyuki Miyachi Strategic Planning Department, Strategic Planning Office, National Institute of Information and Communications Technology Kensuke Fukuda Department of Informatics, School of Multidisciplinary Sciences, The Graduate University of Advanced Studies, Sokendai 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. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 2352-3727 11 2 2025 Advancements in systemic therapy for muscle-invasive bladder cancer: A systematic review from the beginning to the latest updates 1 13 EN Takafumi Yanagisawa Department of Urology, The Jikei University School of Medicine Akihiro Matsukawa Department of Urology, The Jikei University School of Medicine Jeremy Yuen-Chun Teoh Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Keiichiro Mori Department of Urology, The Jikei University School of Medicine Tatsushi Kawada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Paweł Rajwa Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Fahad Quhal Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Benjamin Pradere Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Marco Moschini Department of Urology, San Raffaele Hospital and Scientific Institute Shahrokh F. Shariat Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Jun Miki Department of Urology, The Jikei University School of Medicine Takahiro Kimura Department of Urology, The Jikei University School of Medicine 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).<br> Objective: To synthesize the growing evidence on the efficacy and safety of systemic therapies for MIBC utilizing the data from RCTs.<br> 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).<br> 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.<br> 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. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 0258-851X 39 5 2025 Accuracy of Contrast-enhanced CT in Diagnosing Small-sized cT3a Renal Cell Carcinoma and Analysis of Factors Predicting Downstaging to pT1 2787 2793 EN KENSUKE BEKKU Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences KASUMI YOSHINAGA Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences SHOTA INOUE Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences YOSUKE MITSUI Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences TOMOAKI YAMANOI Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences TATSUSHI KAWADA Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences YUSUKE TOMINAGA Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences TAKUYA SADAHIRA Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences SATOSHI KATAYAMA Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences TAKEHIRO IWATA Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences SHINGO NISHIMURA Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences KOHEI EDAMURA Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences TOMOKO KOBAYASHI Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences MOTOO ARAKI Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background/Aim: This study assessed the accuracy of preoperative contrast-enhanced computed tomography (CECT) scans in staging small-sized, locally advanced (cT3a) renal cell carcinoma (RCC) and identified predictors of pathological downstaging following surgery.<br> Patients and Methods: Seventy-six patients who underwent radical nephrectomy for cT3aN0M0 RCC with tumors ≤7 cm were analyzed. Preoperative CECT evaluated features such as venous, peritumoral, or renal sinus fat, and urinary tract invasion, predictive values, and concordance index between radiological and pathological findings were calculated for these categories. The study also examined the impact of clinicopathologic factors on downstaging.<br> Results: Of 76 patients with cT3 RCC, 37% were down-staged to pT1. Down-staged cases had a higher proportion of male patients and non-clear cell carcinoma (86% vs. 58%, 32% vs. 6%; p=0.02, p=0.007, respectively). Multiple cT3a factors were less common in down-staged cases (4% vs. 23%, p=0.04). Non-clear cell carcinoma was significantly associated with downstaging compared to clear cell carcinoma (75% vs. 30%, p=0.006). Multivariate analysis confirmed non-clear cell carcinoma as an independent predictor (odds ratio=8.2, p=0.01). For venous invasion, CECT sensitivity and positive predictive value were high (73.5% and 83.3%, respectively) and the degree of agreement was substantial (κ=0.62).<br> Conclusion: The accuracy of preoperative CECT was acceptable for detecting venous invasion. The downstaging to pT1 occurred in 37% of cT3a RCC cases in the final pathology, with non-clear cell carcinoma being a significant predictor.<br> No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1999-5903 17 8 2025 A Verilog Programming Learning Assistant System Focused on Basic Verilog with a Guided Learning Method 333 EN Pin-Chieh Hsieh Department of Electronic Engineering, National Taipei University of Technology Tzu-Lun Fang Department of Electronic Engineering, National Taipei University of Technology Shaobo Jin Department of Information and Communication Systems, Okayama University Yuyan Wang Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Yu-Cheng Fan Department of Electronic Engineering, National Taipei University of Technology With continuous advancements in semiconductor technology, mastering efficient designs of high-quality and advanced chips has become an important part of science and technology education. Chip performances will determine the futures of various aspects of societies. However, novice students often encounter difficulties in learning digital chip designs using Verilog programming, a common hardware design language. An efficient self-study system for supporting them that can offer various exercise problems, such that any answer is marked automatically, is in strong demand. In this paper, we design and implement a web-based Verilog programming learning assistant system (VPLAS), based on our previous works on software programming. Using a heuristic and guided learning method, VPLAS leads students to learn the basic circuit syntax step by step, until they acquire high-quality digital integrated circuit design abilities through self-study. For evaluation, we assign the proposal to 50 undergraduate students at the National Taipei University of Technology, Taiwan, who are taking the introductory chip-design course, and confirm that their learning outcomes using VPLAS together are far better than those obtained when following a traditional method. In our final statistics, students achieved an average initial accuracy rate of over 70% on their first attempts at answering questions after learning through our website’s tutorials. With the help of the system’s instant automated grading and rapid feedback, their average accuracy rate eventually exceeded 99%. This clearly demonstrates tha No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Continuous glucose monitoring reveals periodontitis-induced glucose variability, insulin resistance, and gut microbiota dysbiosis in mice 34768 EN Moyuka Kubota-Takamori Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Omori Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chiaki Kamei-Nagata Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Fumiko Kiyama Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayuki Ishii Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaaki Nakayama Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Kimito Hirai Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Yuki Shinoda-Ito Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Okubo Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Shin Nakamura Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsushi Ikeda Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Tsugumichi Saito Department of Health & Sports Sciences, Faculty of Education, Tokyo Gakugei University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Takashiba Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Diabetes mellitus (DM) management has advanced from self-monitoring blood glucose (SMBG) to continuous glucose monitoring (CGM), which better prevents complications. However, the influence of periodontitis—a common DM complication—on glucose variability is unclear. This study examined glucose variability in mice with periodontitis using CGM. Periodontitis was induced in 9-week-old male C57BL/6J mice via silk ligatures around the upper second molars. Glucose levels were monitored over 14 days with CGM, validated by SMBG. On day 14, samples were collected to assess alveolar bone resorption and serum levels of tumor necrosis factor-α (TNF-α), insulin, and amyloid A. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were conducted to evaluate insulin resistance. Gut microbiota diversity was also analyzed. By day 10, mice with periodontitis exhibited higher mean glucose levels and time above range than controls. On day 14, serum insulin and amyloid A levels significantly increased, while TNF-α remained unchanged. GTT and ITT indicated insulin resistance. Microbiota analysis showed reduced alpha- and altered beta-diversity, with decreased Coprococcus spp. and increased Prevotella spp., linking dysbiosis to insulin resistance. Periodontitis disrupts glucose regulation by promoting insulin resistance and gut microbiota imbalance, leading to significant glucose variability. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1573-7209 28 4 2025 Cancer-associated fibroblast-derived SOD3 enhances lymphangiogenesis to drive metastasis in lung adenocarcinoma 51 EN May Wathone Oo Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takao Hikita Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoha Mashima Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kosuke Torigata School of Medicine, Kobe University Yin Min Thu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Habu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Sachio Ito Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hitoshi Nagatsuka Department of Thoracic Surgery, National Hospital Organization, Shikoku Cancer Center Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masanori Nakayama Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1342-1751 29 5 2025 Development and validation of an algorithm for identifying patients undergoing dialysis from patients with advanced chronic kidney disease 650 661 EN Takahiro Imaizumi Department of Nephrology, Nagoya University Graduate School of Medicine Takashi Yokota Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital Kouta Funakoshi Kyusyu University Hospital Kazushi Yasuda Department of Nephrology, Nagoya University Graduate School of Medicine Akiko Hattori Department of Nephrology, Nagoya University Graduate School of Medicine Akemi Morohashi Department of Advanced Medicine, Nagoya University Hospital Tatsumi Kusakabe Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital Masumi Shojima Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University Sayoko Nagamine Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University Toshiaki Nakano Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University Yong Huang Division of Medical Informatics, Okayama University Hospital Hiroshi Morinaga Department of Comprehensive Therapy for Chronic Kidney Disease, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miki Ohta Clinical Research Promotion Center, The University of Tokyo Hospital Satomi Nagashima Department of Healthcare Information Management, The University of Tokyo Hospital Ryusuke Inoue Medical Information Technology Center, Tohoku University Hospital Naoki Nakamura Medical Information Technology Center, Tohoku University Hospital Hideki Ota Medical Information Technology Center, Tohoku University Hospital Tatsuya Maruyama Clinical Research Promotion Center, The University of Tokyo Hospital Hideo Gobara Division of Medical Informatics, Okayama University Hospital Akira Endoh Department of Medical Informatics, Hokkaido University Hospital Masahiko Ando Department of Nephrology, Nagoya University Graduate School of Medicine Yoshimune Shiratori Medical IT Center, Nagoya University Hospital Shoichi Maruyama Department of Nephrology, Nagoya University Graduate School of Medicine 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.<br> 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.<br> 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.<br> 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. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0273-1177 76 9 2025 Spatiotemporal evolution of ecosystem carbon storage under land use/land cover dynamics in the coastal region of Central Vietnam 4815 4837 EN Viet Hoang Ho Graduate School of Environmental and Life Science, Okayama University Hidenori Morita Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Thanh Ha Ho University of Agriculture and Forestry, Hue University Felix Bachofer German Aerospace Center (DLR), Earth Observation Center 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. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 26 19 2025 Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: From Sarcomere to Clinic 9347 EN Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Okumura Department of Advanced Cardiovascular Therapeutics, Nagoya University Graduate School of Medicine Seiya Kato Division of Pathology, Saiseikai Fukuoka General Hospital Kenji Onoue Department of Cardiovascular Medicine, Nara Medical University Toru Kubo Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University Hidemichi Kouzu Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine Toshiyuki Yano Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine Takayuki Inomata Department of Cardiovascular Medicine, Niigata University Graduate School of Medical and Dental Sciences Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease characterized by unexplained left ventricular hypertrophy, often resulting from pathogenic variants of sarcomeric protein genes. Conventional treatments, such as the use of beta blockers or calcium channel blockers, focus on symptomatic control but do not address the underlying hypercontractility at the sarcomere level. Recent advances in molecular understanding have led to the development of cardiac myosin inhibitors that directly modulate sarcomeric function by reducing myosin–actin cross-bridge formation and adenosine triphosphatase (ATPase) activity. Mavacamten and aficamten have shown promising results in phase 2 and 3 clinical trials, improving symptoms, exercise capacity, and left ventricular outflow tract gradients in patients with obstructive HCM. This review summarizes the current understanding of HCM pathophysiology, diagnostic strategies, and conventional treatments with a focus on the mechanisms of action of myosin inhibitors, clinical evidence supporting their use, and future directions for improvement. We also discuss their potential applications in non-obstructive HCM and the importance of precision medicine guided by genetic profiling. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6643 17 18 2025 Lacticaseibacillus rhamnosus Probio-M9 Alters the Gut Microbiota and Mitigates Pulmonary Hypertension in a Rat Model 2927 EN Zhixin Zhao 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 Gaopeng Li Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University Kiyomi Ohmichi Department of Diagnostic Pathology, Kagawa University Hospital Xiaodong Li Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University Feiyan Zhao 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 Kaori Ishikawa Department of General Medicine, Kagawa University Hospital Ryou Ishikawa Department of Diagnostic Pathology, Kagawa University Hospital Kazufumi Nakamura Center for Advanced Heart Failure, Okayama University Hospital Naoya Yokota Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University Zhihong Sun 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 Lin Hai Kurahara Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University 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. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2041-1723 16 1 2025 Persistent homology elucidates hierarchical structures responsible for mechanical properties in covalent amorphous solids 8226 EN Emi Minamitani SANKEN, The University of Osaka Takenobu Nakamura Department of Materials and Chemistry Materials DX Research Center, National Institute of Advanced Industrial Science and Technology (AIST) Ippei Obayashi Center for Artificial Intelligence and Mathematical Data Science, Okayama University Hideyuki Mizuno Graduate School of Arts and Sciences, The University of Tokyo Understanding how atomic-level structures govern the mechanical properties of amorphous materials remains a fundamental challenge in solid-state physics. Under mechanical loading, amorphous materials exhibit simple affine and spatially inhomogeneous nonaffine displacements that contribute to the elastic modulus through the Born (affine) and nonaffine terms, respectively. The differences between soft local structures characterized by small Born terms or large nonaffine displacements have yet to be elucidated. This challenge is particularly complex in covalent amorphous materials such as silicon, where the medium-range order (MRO) plays a crucial role in the network structure. To address these issues, we combined molecular dynamics simulations with persistent homology analysis. Our results reveal that local structures with small Born terms are governed by short-range characteristics, whereas those with large nonaffine displacements exhibit hierarchical structures in which short-range disorder is embedded within the MRO. These hierarchical structures are also strongly correlated with low-energy localized vibrational excitations. Our findings demonstrate that the mechanical responses and dynamic properties of covalent amorphous materials are intrinsically linked to the MRO, providing a framework for understanding and tailoring their properties. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Pharmacokinetics and the effectiveness of pyrogen-free bioabsorbable wet adhesives 20056 EN Risa Oshima Department of Periodontology, Faculty of Dental Medicine, Hokkaido University Kumiko Yoshihara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ko Nakanishi Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Tsukasa Akasaka Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Shinji Shimoji Department of Periodontology, Faculty of Dental Medicine, Hokkaido University Teppei Nakamura Department of Applied Veterinary Science, Faculty of Veterinary Medicine, Hokkaido University Takumi Okihara Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Mariko Nakamura Department of Clinical Psychology, School of Clinical Psychology, Kyushu University of Medical and Science Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ikkei Tamada Department of Plastic and Reconstructive Surgery, Tokyo Metropolitan Children’s Medical Center Bart Van Meerbeek BIOMAT, Department of Oral Health Sciences, & UZ Leuven, Dentistry, KU Leuven Tsutomu Sugaya Department of Periodontology, Faculty of Dental Medicine, Hokkaido University Yasuhiro Yoshida Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Bioabsorbable materials are essential for advanced therapies, including surgical sealing, cell therapy, and drug delivery. Natural bioabsorbable materials, including collagen and hyaluronic acid, have better biocompatibility than synthetic bioabsorbable polymers; however, they are mainly derived from animals, presenting infection risks. Non-animal origin polymers have a lower molecular weight than those of animal origins. Their viscosity increases with increase in molecular weight, making endotoxin removal difficult. Here, using the phosphoryl chloride disposal method, we present a strategy for synthesizing pyrogen-free bioabsorbable adhesives with controlled molecular weight. Phosphopullulan, a polysaccharide derivative, had less than detectable endotoxin levels and controllable average molecular weight of approximately 300,000 to over 1,400,000. Furthermore, it is important to ensure the safety as well as efficacy of bio-implantable materials. We have evaluated the biosafety of polysaccharide derivatives we are developing, and have examined their cell phagocytosis and pharmacokinetics in vitro and in vivo, and have confirmed that they are safe. We have also evaluated their adhesion to wet tissue adhesions and confirmed that they leak less than existing materials. No potential conflict of interest relevant to this article was reported.

American Association for the Advancement of Science (AAAS) Acta Medica Okayama 2375-2548 11 38 2025 Polymeric microwave rectifiers enabled by monolayer-thick ionized donors eadv9952 EN Nobutaka Osakabe Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Jeongeun Her Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Takahiro Kaneta Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Akiko Tajima Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Elena Longhi School of Chemistry and Biochemistry and Center for Organic Photonics and Electronics, Georgia Institute of Technology Kan Tang Renewable and Sustainable Energy Institute, University of Colorado Boulder Kazuhiro Fujimori Faculty of Environmental, Life, Natural Science and Technology, Okayama University Stephen Barlow School of Chemistry and Biochemistry and Center for Organic Photonics and Electronics, Georgia Institute of Technology Seth R. Marder School of Chemistry and Biochemistry and Center for Organic Photonics and Electronics, Georgia Institute of Technology Shun Watanabe Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Jun Takeya Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Yu Yamashita Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Solution processing of polymeric semiconductors provides a facile way to fabricate functional diodes. However, energy barriers at metal-semiconductor interfaces often limit their performance. Here, we report rectifying polymer diodes with markedly modified energy-level alignments. The gold electrode surface was treated with a dimeric metal complex, which resulted in a shallow work function of 3.7 eV by forming a monolayer-thick ionized donor layer. When a polymeric semiconductor was coated on the treated electrode, most of the ionized donors remained at the metal-semiconductor interface. The confined ionized donors with the ideal thickness enabled fabrication of a polymer diode with a forward current density of over 100 A cm−2. Furthermore, a power conversion efficiency of 7.9% was observed for rectification at a microwave frequency of 920 MHz, which is orders of magnitude higher than that reported for organic diodes. Our findings will pave a way to solution-processed high-frequency and high-power devices. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2504-446X 9 9 2025 Application of LMM-Derived Prompt-Based AIGC in Low-Altitude Drone-Based Concrete Crack Monitoring 660 EN Shijun Pan Shenzhen Institute for Advanced Study, UESTC, University of Electronic Science and Technology of China Zhun Fan Shenzhen Institute for Advanced Study, UESTC, University of Electronic Science and Technology of China Keisuke Yoshida Graduate School of Environmental and Life Science, Okayama University Shujia Qin Shenzhen Academy of Robotics Takashi Kojima TOKEN C.E.E. Consultants Co., Ltd. Satoshi Nishiyama Graduate School of Environmental and Life Science, Okayama University 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. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1472-6831 25 1 2025 Phosphorylated pullulan as a local drug delivery matrix for cationic antibacterial chemicals to prevent oral biofilm 1333 EN Naoko Namba-Koide Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Yasuhiro Yoshida Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Takumi Okihara Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Yusuke Kawata Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Masahiro Ito Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Takashi Ito Center for Innovative Clinical Medicine, Okayama University Hospital Kazu Takeuchi-Hatanaka Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Yuki Shinoda-Ito Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Omori Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yamamoto Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Takashiba Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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.<br> 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.<br> 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.<br> Conclusions The combination of PP and CPC may contribute to the low concentration and effective prevention of oral infections, such as dental caries. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 2050-7488 13 35 2025 Thermally polymerizable phthalocyanine realizes a metal–nitrogen-doped carbon material featuring a defined single-atom catalyst motif with CO2RR activity 28887 28895 EN Yuki Sano Department of Chemistry, Graduate School of Science, Tohoku University Daichi Nakajima Department of Chemistry, Graduate School of Science, Tohoku University Biplab Manna Center for Basic Research on Materials, National Institute for Materials Science Koki Chida Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Ryojun Toyoda Department of Chemistry, Graduate School of Science, Tohoku University Shinya Takaishi Department of Chemistry, Graduate School of Science, Tohoku University Kazuyuki Iwase Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Koji Harano Center for Basic Research on Materials, National Institute for Materials Science Yuta Nishina Graduate School of Natural Science and Technology, Okayama University Takeharu Yoshii Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Ryota Sakamoto Department of Chemistry, Graduate School of Science, Tohoku University Metal–nitrogen-doped carbon materials (MNCs) exhibit good electrocatalytic performance owing to the intrinsic advantages of carbon-based materials and the presence of isolated and stabilized metal atoms coordinated by nitrogen sites. However, conventional high-temperature pyrolysis of precursor molecules make it difficult to control the coordination structure precisely. To address this issue, here we report a new synthesis strategy for MNCs. Specifically, we design and synthesize Ni-phthalocyanine functionalized with ethynyl groups as solid-state thermal polymerization points. After depositing the Ni-phthalocyanine precursor on a carbon support and performing a thermal treatment, the resultant carbon composite material features a Ni–N4 coordination structure derived from the precursor, and enhanced porosity. This material demonstrates high catalytic activity for the CO2 reduction reaction (CO2RR). Our synthetic approach is applicable to various precursor molecules and carbon supports, paving the way for the further development of MNC-based electrode catalysts. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0008-6223 243 2025 Organic solvent transport through reduced graphene oxide membranes with controlled oxygen content 120539 EN Hongzhe Chen School of Materials Science and Engineering, University of New South Wales Sydney Tongxi Lin School of Materials Science and Engineering, University of New South Wales Sydney Zeno Rizqi Ramadhan Electron Microscope Unit, University of New South Wales Aditya Rawal Mark Wainwright Analytical Centre, University of New South Wales Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Amir Karton School of Science and Technology, University of New England Xiaojun Ren School of Materials Science and Engineering, University of New South Wales Sydney Rakesh Joshi School of Materials Science and Engineering, University of New South Wales Sydney 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. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2399-3669 7 1 2024 Post-spinel-type AB2O4 high-pressure phases in geochemistry and materials science 189 EN Masaki Akaogi Department of Chemistry, Gakushuin University Takayuki Ishii Institute for Planetary Materials, Okayama University Kazunari Yamaura Research Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science Post-spinel-type AB2O4 compounds are stable at higher pressures than spinel phases. These compounds have garnered much interest in geo- and materials science for their geochemical importance as well as potential application as high ionic conductors and materials with strongly correlated electrons. Here, large-volume high-pressure syntheses, structural features and properties of post-spinels are reviewed. Prospects are discussed for future searches for post-spinel-type phases by applying advanced large-volume high-pressure technology. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2694-2496 2025 RNA Delivery Using a Graphene Oxide-Polyethylenimine Hybrid Inhibiting Myotube Differentiation EN Koji Matsuura CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR3572, University of Strasbourg, ISIS Giacomo Reina CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR3572, University of Strasbourg, ISIS Zhengfeng Gao CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR3572, University of Strasbourg, ISIS Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Alberto Bianco CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR3572, University of Strasbourg, ISIS Graphene oxide (GO) conjugated with short polyethylenimine (PEI) chains (GO-PEI) has been designed as a candidate nanocarrier for small interfering RNA (siRNA) delivery to mammalian cells based on the efficient interaction between the positively charged GO-based platform and the negatively charged siRNA. The function and efficiency of siRNA delivery using GO-PEI were compared to those using the positive control Lipofectamine RNAiMax by analyzing the differentiation to myotubes, and myogenin gene and protein expression in C2C12 cells. RNAiMax transfection induced cellularization and reduction of both myogenin gene and protein expression, suggesting that the differentiation of C2C12 cells was triggered by gene silencing. While GO-PEI also promoted cellularization, the myogenin gene expression remained comparable to scrambled controls, whereas the protein levels were higher than those observed with RNAiMax. Mechanistically, we attributed the reduced gene silencing efficiency of GO-PEI to a poor endosomal escape, despite strong siRNA complexation. This limitation was likely due to a low buffering capacity of GO-PEI, as a significant fraction of nitrogen atoms were already protonated, reducing the availability of free amines necessary for endosomal disruption. An appropriate chemical modification to enhance siRNA release from the endosomes is therefore essential for advancing the development of GO-based platforms as versatile and efficient nanocarriers in gene therapy applications. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2640-4567 2025 Integration of Cholesterol Oxidase‐Based Biosensors on a Smart Contact Lens for Wireless Cholesterol Monitoring from Tears 2500368 EN Yang Cui Graduate school of Information, Production and Systems, Waseda University Lin Zhuo Graduate school of Information, Production and Systems, Waseda University Yuta Nishina Graduate School of Natural Science and Technology, Okayama University Saman Azhari Graduate school of Information, Production and Systems, Waseda University Takeo Miyake Graduate school of Information, Production and Systems, Waseda University Cholesterol plays a critical role in physiological functions, but elevated levels increase the risk of cardiovascular disease. Regular cholesterol monitoring is essential for elderly or obese individuals. Current methods, such as blood tests, are invasive, inconvenient, and require a professional operator. In contrast, tears, as an accessible body fluid, offer a promising alternative for noninvasive monitoring due to their correlation with blood cholesterol levels. Herein, a noninvasive approach for monitoring cholesterol levels in tears using a biosensor integrated into a smart contact lens is reported. The biosensor employs cholesterol oxidases as the biocatalyst, coupled with an osmium-based mediator, to detect cholesterol concentrations ranging from 0.1 mM to 1.2 mM in artificial tears. A key challenge is the extremely low cholesterol concentration in tears, which is addressed using a parity-time (P-T) symmetry-based magnetic resonance coupling system. This system enables wireless signal reading and achieves high sensitivity due to its high-quality (Q) factor, which can achieve a detection limit of 0.061 mM. This portable, high-sensitivity smart contact lens demonstrates significant potential as a wearable device for continuous, noninvasive cholesterol monitoring. The findings contribute to advancing tear-based diagnostic systems and highlight the scientific importance of utilizing tear biomarkers for health monitoring. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 14 17 2025 Photon-Counting CT Enhances Diagnostic Accuracy in Stable Coronary Artery Disease: A Comparative Study with Conventional CT 6049 EN Mitsutaka Nakashima Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Hara Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryosuke Miyagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Nishihara Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Miki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Osawa Department of General Internal Medicine 3, Kawasaki Medical School General Medicine Centre Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Objectives: Coronary CT angiography (CCTA) is a cornerstone in evaluating stable coronary artery disease (CAD), but conventional energy-integrating detector CT (EID-CT) has limitations, including calcium blooming and limited spatial resolution. Photon-counting detector CT (PCD-CT) may overcome these drawbacks through enhanced spatial resolution and improved tissue characterization. Methods: In this retrospective, propensity score–matched study, we compared CCTA findings from 820 patients (410 per group) who underwent either EID-CT or PCD-CT for suspected stable CAD. Primary outcomes included stenosis severity, high-risk plaque features, and downstream invasive coronary angiography (ICA) referral and yield. Results: The matched cohorts were balanced in demographics and cardiovascular risk factors (mean age 67 years, 63% male). PCD-CT showed a favorable shift in stenosis severity distribution (p = 0.03). High-risk plaques were detected less frequently with PCD-CT (22.7% vs. 30.5%, p = 0.01). Median coronary calcium scores did not differ (p = 0.60). Among patients referred for ICA, those initially evaluated with PCD-CT were more likely to undergo revascularization (62.5% vs. 44.1%), and fewer underwent potentially unnecessary ICA without revascularization (3.7% vs. 8.0%, p = 0.001). The specificity in diagnosing significant stenosis requiring revascularization was 0.74 with EID-CT and 0.81 with PCD-CT (p = 0.04). Conclusions: PCD-CT improved diagnostic specificity for CAD, reducing unnecessary ICA referrals while maintaining detection of clinically significant disease. This advanced CT technology holds promise for more accurate, efficient, and patient-centered CAD evaluation. No potential conflict of interest relevant to this article was reported.

Elsevier B.V. Acta Medica Okayama 0304-4165 1869 12 2025 The F54L mutation of Thioredoxin shows protein instability and increased fluctuations of the catalytic center 130860 EN Takumi Baba Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center Go Ueno Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center Chika Ohe Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center Shuku Saji Structural Biology Division, Japan Synchrotron Radiation Research Institute Sachiko Yamamoto Structural Biology Division, Japan Synchrotron Radiation Research Institute Masaki Yamamoto Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center Hiroshi Nakagawa Materials Sciences Research Center, Japan Atomic Energy Agency Nobuo Okazaki Neutron Science and Technology Center, Comprehensive Research Organization for Science and Society (CROSS) Mamoru Ouchida Department of Molecular Oncology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Iori Kawasaki-Ohmori Section of Developmental Physiology and Pathology, Faculty of Education, Okayama University Kohei Takeshita Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center Thioredoxin is a ubiquitous redox protein that acts as an electron donor via its conserved dithiol motif (C32GPC35), catalyzing dithiol–disulfide exchange to regulate the redox state of target proteins. It supports antioxidant defense via peroxiredoxins, facilitates DNA synthesis by donating electrons to ribonucleotide reductase, and regulates redox-sensitive signaling pathways, including those controlling transcription and apoptosis. Neuronal degeneration and chronic kidney disease have been observed in Txn-F54L mutant rats; however, the details of why the Txn mutation causes these phenomena remain unknown. The present study aimed to elucidate the functional and structural changes caused by the F54L mutation. The Thioredoxin-F54L showed less insulin-reducing activity and more thermosensitivity to denaturation in the body temperature range compared to the wild type. The crystal structure revealed that F54 forms hydrophobic interactions with the surrounding hydrophobic amino acids. In addition, molecular dynamics simulation predicts increased fluctuations around the F54L mutation and a tendency for the distance between residues C32 and C35 at the catalytic center to be widened. The increased distance between residues C32 and C35 of the catalytic center may affect the reducing activity of the enzyme on the substrate. The finding that Thioredoxin-F54L is prone to denaturation at normal body temperature may reduce the normally functioning Thioredoxin. These molecular characteristics of Thioredoxin-F54L may be related to brain and kidney disease development in the Txn-F54L rats. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0032-0781 2025 Thylakostasis: key factors in thylakoid membrane organization with emphasis on biogenesis and remodeling proteins in vascular plants pcaf098 EN Wataru Sakamoto Institute of Plant Science and Resources, Okayama University The thylakoid membrane (TM), a defining feature for almost all oxygen-evolving photosynthetic organisms, serves as the structural foundation for light-driven energy conversion. In vascular plants, the TM evolved into a complex architecture composed of single-layered stroma thylakoids and stacked grana thylakoids, enabling the spatial organization of two photosystems (PSII and PSI) to optimize light capture and energy transfer. In addition, two membrane regions, one connecting these two compartments (grana margin) and the other corresponding to the curvature domain in grana, function in dissipating excess energy, balancing electron transfer, and maintaining functional PSII. Recent advances in electron microscopy imaging and proteome analysis of membrane subcompartments have provided new insights into the structure and dynamic adaptations of the TM in response to diverse environmental conditions. To describe the mechanisms that govern TM architecture, dynamics, and integrity, I am introducing the concept of “thylakostasis” (thylakoid homeostasis). Here, I provide an overview of the molecular components and processes central to thylakostasis, including the biosynthesis of lipids, chlorophyll, and proteins. I focus particularly on the membrane remodeling proteins whose functions have been elucidated recently, such as VIPP1, a member of the evolutionarily conserved PspA/ESCRT-III superfamily; FZL, a dynamin-like GTPase; and CURT1, a curvature-inducing protein unique to photosynthetic organisms. Together, these factors orchestrate TM biogenesis, remodeling, and adaptive flexibility that is essential for photosynthetic efficiency. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1475-2867 25 1 2025 Precise stratification of prognosis in pancreatic ductal adenocarcinoma patients based on pre- and postoperative genomic information 305 EN Kokichi Miyamoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Toshiaki Takahashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Moriwake Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masashi Kayano Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takeyoshi Nishiyama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hideki Yamamoto Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mizuki Morita Department of Biomedical Informatics, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 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.<br> 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.<br> 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.<br> 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. No potential conflict of interest relevant to this article was reported.

American Institute of Mathematical Sciences (AIMS) Acta Medica Okayama 2377-9098 12 3 2025 Biophysical regulation of extracellular matrix in systemic lupus erythematosus 412 437 EN Qiwei Li Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Qiang Li Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Zhaoyang Xiao Department of Anesthesiology, The Second Affiliated Hospital of Dalian Medical University Keiji NARUSE Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Takahashi Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by immune dysregulation and multi-organ damage. Recent advances have underscored the critical involvement of extracellular matrix (ECM) biophysical properties in shaping immune cell behavior and metabolic states that contribute to disease progression. This review systematically delineates the pathological remodeling of ECM biophysics in SLE, with a focus on their roles in mechanotransduction, immune-metabolic interplay, and organ-specific tissue injury. By integrating current evidence, we highlight how ECM-derived mechanical cues orchestrate aberrant immune responses and propose new perspectives for targeting ECM-immune crosstalk in the development of organ-specific, mechanism-based therapies for SLE. No potential conflict of interest relevant to this article was reported.

IOP Publishing Acta Medica Okayama 1882-0778 18 9 2025 Fundamentals and advances in transverse thermoelectrics 090101 EN Hiroto Adachi Research Institute for Interdisciplinary Science, Okayama University Fuyuki Ando Research Center for Magnetic and Spintronic Materials, National Institute for Materials Science Takamasa Hirai Research Center for Magnetic and Spintronic Materials, National Institute for Materials Science Rajkumar Modak Research Center for Magnetic and Spintronic Materials, National Institute for Materials Science Matthew A. Grayson Department of Electrical and Computer Engineering, Northwestern University Ken-ichi Uchida Research Center for Magnetic and Spintronic Materials, National Institute for Materials Science Transverse thermoelectric effects interconvert charge and heat currents in orthogonal directions due to the breaking of either time-reversal symmetry or structural symmetry, enabling simple and versatile thermal energy harvesting and solid-state cooling/heating within single materials. In comparison to the complex module structures required for the conventional Seebeck and Peltier effects, the transverse thermoelectric effects provide the complete device structures, potentially resolving the fundamental issue of multi-module degradation of thermoelectric conversion performance. This review article provides an overview of all currently known transverse thermoelectric conversion phenomena and principles, as well as their characteristics, and reclassifies them in a unified manner. The performance of the transverse thermoelectric generator, refrigerator, and active cooler is formulated, showing that thermal boundary conditions play an essential role in discussion on their behaviors. Examples of recent application research and material development in transverse thermoelectrics are also introduced, followed by a discussion of future prospects. No potential conflict of interest relevant to this article was reported.

Institute of Electrical and Electronics Engineers (IEEE) Acta Medica Okayama 2169-3536 13 2025 Security in Post-Quantum Era: A Comprehensive Survey on Lattice-Based Algorithms 89003 89024 EN Hien Nguyen School of Informatics, Computing, and Cyber Systems, Northern Arizona University Samsul Huda Interdisciplinary Education and Research Field, Okayama University Yasuyuki Nogami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tuy Tan Nguyen School of Informatics, Computing, and Cyber Systems, Northern Arizona University 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. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1752-8054 18 8 2025 Cardiotoxicity Assessment of EGFR Tyrosine Kinase Inhibitors Using Human iPS Cell‐Derived Cardiomyocytes and FDA Adverse Events Reporting System e70325 EN Shota Yanagida Division of Pharmacology, National Institute of Health Sciences (NIHS) Hiroyuki Kawagishi Division of Pharmacology, National Institute of Health Sciences (NIHS) Mitsuo Saito Japan Pharmaceutical Information Center (JAPIC) Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Yoshito Zamami Department of Pharmacy, Okayama University Hospital Yasunari Kanda Division of Pharmacology, National Institute of Health Sciences (NIHS) 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. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0753-3322 188 2025 Unravelling the cardioprotective effects of calcitriol in Sunitinib-induced toxicity: A comprehensive in silico and in vitro study 118137 EN Yoshika Sakamoto Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Takahiro Niimura Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Mitsuhiro Goda Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Nanami Tomochika Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Wakana Murakawa Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Fuka Aizawa Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Kenta Yagi Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Yuki Izawa-Ishizawa Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Yoshito Zamami Department of Pharmacy, Okayama University Hospital Keisuke Ishizawa Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences 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. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 1468-6996 26 1 2025 Quantitative measurements of transverse thermoelectric generation and cooling performances in SmCo5/Bi0.2Sb1.8Te3-based artificially tilted multilayer module 2535955 EN Masayuki Murata Research Institute for Energy Conservation, National Institute of Advanced Industrial Science and Technology Fuyuki Ando Research Center for Magnetic and Spintronic Materials, National Institute for Materials Science Takamasa Hirai Research Center for Magnetic and Spintronic Materials, National Institute for Materials Science Hiroto Adachi Research Institute for Interdisciplinary Science, Okayama University Ken-ichi Uchida Research Center for Magnetic and Spintronic Materials, National Institute for Materials Science The transverse thermoelectric generation and cooling performances in a thermopile module composed of recently developed SmCo5/Bi0.2Sb1.8Te3 artificially tilted multilayers are evaluated quantitatively. When a large temperature difference of 405°C is applied to the SmCo5/Bi0.2Sb1.8Te3-based module, the open-circuit voltage and output power reach 0.51 V and 0.80 W, respectively. The corresponding maximum power density is 0.16 W/cm2, even if the power is normalized by the device area including areas that do not contribute to the power generation, such as epoxy resin, electrodes, and insulating layers. The maximum energy conversion efficiency for our module in this condition is experimentally determined to be 0.92%. Under the cooling operation, the same module exhibits the maximum temperature difference of 9.0°C and heat flow at the cold side of 1.6 W. Although these values are lower than the ideal thermoelectric performance expected from the material parameters due to the imperfections associated with modularization, the systematic investigations reported here clarify a potential of the SmCo5/Bi0.2Sb1.8Te3 artificially tilted multilayers as thermoelectric generators and cooling devices. No potential conflict of interest relevant to this article was reported.

International Union of Crystallography (IUCr) Acta Medica Okayama 1600-5775 32 5 2025 X-ray fluorescence holography under high-pressure conditions 1302 1309 EN Xinhui Zhan Graduate School of Advanced Science and Engineering, Hiroshima University Naoki Ishimatsu Geodynamics Research Center, PIAS, Ehime University Koji Kimura Department of Physical Science and Engineering, Nagoya Institute of Technology Naohisa Happo Graduate School of Information Sciences, Hiroshima City University Halubai Sekhar Institute of Industrial Nanomaterials, Kumamoto University Tomoko Sato Institute of Materials Structure Science, High Energy Accelerator Research Organization, KEK Nobuo Nakajima Graduate School of Advanced Science and Engineering, Hiroshima University Naomi Kawamura Japan Synchrotron Radiation Research Institute, SPring-8 Kotaro Higashi Japan Synchrotron Radiation Research Institute, SPring-8 Oki Sekizawa Japan Synchrotron Radiation Research Institute, SPring-8 Hirokazu Kadobayashi Japan Synchrotron Radiation Research Institute, SPring-8 Ritsuko Eguchi Graduate School of Science, University of Hyogo Yoshihiro Kubozono Research Institute for Interdisciplinary Science, Okayama University Hiroo Tajiri Japan Synchrotron Radiation Research Institute, SPring-8 Shinya Hosokawa Faculty of Materials for Energy, Shimane University Tomohiro Matsushita Graduate School of Science and Technology, Nara Institute of Science and Technology Toru Shinmei Geodynamics Research Center, PIAS, Ehime University Tetsuo Irifune Geodynamics Research Center, PIAS, Ehime University Koichi Hayashi Department of Physical Science and Engineering, Nagoya Institute of Technology 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. No potential conflict of interest relevant to this article was reported.

Fuji Technology Press Ltd. Acta Medica Okayama 1883-8030 20 4 2025 High-Definition Topographic Archiving and Educational Applications in Regions Affected by the 2024 Noto Peninsula Earthquake 401 409 EN Takuro Ogura Graduate School of Education, Hyogo University of Teacher Education Hiroyuki Yamauchi Art Research Center, Ritsumeikan University Tatsuto Aoki Faculty of Regional Development Studies, Kanazawa University Nobuhisa Matta Graduate School of Education, Okayama University Kotaro Iizuka Center for Spatial Information Science, The University of Tokyo Yoshiya Iwasa Faculty of Education, University of Teacher Education Fukuoka Takayuki Takahashi International Research Institute of Disaster Science, Tohoku University Kiyomi Hayashi Faculty of Regional Development Studies, Kanazawa University Tsuyoshi Hattanji Institute of Life and Environmental Sciences, University of Tsukuba Takashi Oguchi Center for Spatial Information Science, The University of Tokyo 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. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0091-6749 156 2 2025 Dried blood spot proteome identifies subclinical interferon signature in neonates with type I interferonopathy 473 479.e1 EN Hiroshi Nihira Department of Pediatrics, Kyoto University Graduate School of Medicine Daisuke Nakajima Department of Applied Genomics, Kazusa DNA Research Institute Kazushi Izawa Department of Pediatrics, Kyoto University Graduate School of Medicine Yusuke Kawashima Department of Applied Genomics, Kazusa DNA Research Institute Hirofumi Shibata Department of Pediatrics, Kyoto University Graduate School of Medicine Ryo Konno Department of Applied Genomics, Kazusa DNA Research Institute Motoko Higashiguchi Department of Pediatrics, Kyoto University Graduate School of Medicine Takayuki Miyamoto Department of Pediatrics, Kyoto University Graduate School of Medicine Masahiko Nishitani-Isa Department of Pediatrics, Kyoto University Graduate School of Medicine Eitaro Hiejima Department of Pediatrics, Kyoto University Graduate School of Medicine Yoshitaka Honda Department of Pediatrics, Kyoto University Graduate School of Medicine Tadashi Matsubayashi Department of Pediatrics, Seirei Hamamatsu General Hospital Takashi Ishihara Department of Pediatrics, Nara Medical University Masato Yashiro Department of Pediatrics, Okayama University Naomi Iwata Department of Infection and Immunology, Aichi Children’s Health and Medical Center Yoko Ohwada Department of Pediatrics, Dokkyo Medical University School of Medicine Seiichi Tomotaki Department of Pediatrics, Kyoto University Graduate School of Medicine Masahiko Kawai Department of Neonatology, Kyoto University Graduate School of Medicine Kosaku Murakami Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine Hidenori Ohnishi Department of Pediatrics, Gifu University Graduate School of Medicine Masataka Ishimura Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University Satoshi Okada Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences Motoi Yamashita Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) Tomohiro Morio Laboratory of Immunology and Molecular Medicine, Advanced Research Initiative, Institute of Science Tokyo (SCIENCE TOKYO) Akihiro Hoshino Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) Hirokazu Kanegane Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) Kohsuke Imai Department of Pediatrics, National Defense Medical College Yasuko Nakamura Department of Pediatrics, National Defense Medical College Shigeaki Nonoyama Department of Pediatrics, National Defense Medical College Toru Uchiyama Department of Human Genetics, National Center for Child Health and Development Masafumi Onodera Department of Human Genetics, National Center for Child Health and Development Takashi Ishikawa Division of Immunology, National Center for Child Health and Development Toshinao Kawai Division of Immunology, National Center for Child Health and Development Junko Takita Department of Pediatrics, Kyoto University Graduate School of Medicine Ryuta Nishikomori Department of Pediatrics and Child Health, Kurume University School of Medicine Osamu Ohara Department of Applied Genomics, Kazusa DNA Research Institute Takahiro Yasumi Department of Pediatrics, Kyoto University Graduate School of Medicine Background: Type I interferonopathy is characterized by aberrant upregulation of type I interferon signaling. The mRNA interferon signature is a useful marker for activation of the interferon pathway and for diagnosis of type I interferonopathy; however, early diagnosis is challenging.<br> Objective: This study sought to identify the proteomic interferon signature in dried blood spot (DBS) samples. The aim was to evaluate the usefulness of the interferon signature for neonatal screening and to gain insight into presymptomatic state of neonates with inborn errors of immunity (IEIs).<br> Methods: DBS samples from healthy newborns/adults, patients with type I interferonopathy or other IEIs as well as from neonates with viral infections, including some samples obtained during the presymptomatic neonatal period, were examined by nontargeted proteome analyses. Expression of interferon-stimulated genes (ISGs) was evaluated and a DBS-interferon signature was defined. Differential expression/pathway analysis was also performed.<br> Results: The ISG products IFIT5, ISG15, and OAS2 were detected. Expression of IFIT5 and ISG15 was upregulated significantly in individuals with type I interferonopathy. We defined the sum of the z scores for these as the DBS-interferon signature, and found that patients with IEIs other than type I interferonopathy, such as chronic granulomatous disease (CGD), also showed significant elevation. Additionally, neonatal samples of type I interferonopathy and CGD patients showed high interferon signatures. Pathway analysis of neonatal CGD samples revealed upregulation of systemic lupus erythematosus–like pathways.<br> Conclusion: Upregulation of the interferon pathway exists already at birth—not only in neonates with type I interferonopathy but also in other IEIs, including CGD. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1663-9812 16 2025 Histidine-rich glycoprotein inhibits TNF-α–induced tube formation in human vascular endothelial cells 1561628 EN Omer Faruk Hatipoglu Department of Pharmacology, Kindai University Faculty of Medicine Takashi Nishinaka Department of Pharmacology, Kindai University Faculty of Medicine Kursat Oguz Yaykasli Department of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen Shuji Mori Department of Pharmacology, School of Pharmacy, Shujitsu University Masahiro Watanabe Department of Pharmacology, School of Pharmacy, Shujitsu University Takao Toyomura Department of Pharmacology, School of Pharmacy, Shujitsu University Masahiro Nishibori Department of Translational Research and Dug Development, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Hirohata Department of Medical Technology, Graduate School of Health Sciences, Okayama University Hidenori Wake Department of Pharmacology, Kindai University Faculty of Medicine Hideo Takahashi Department of Pharmacology, Kindai University Faculty of Medicine Introduction: Tumor necrosis factor-α (TNF-α)-induced angiogenesis plays a critical role in tumor progression and metastasis, making it an important therapeutic target in cancer treatment. Suppressing angiogenesis can effectively limit tumor growth and metastasis. However, despite advancements in understanding angiogenic pathways, effective strategies to inhibit TNF-α-mediated angiogenesis remain limited.<br> Methods: This study investigates the antiangiogenic effects of histidine-rich glycoprotein (HRG), a multifunctional plasma protein with potent antiangiogenic properties, on TNF-α-stimulated human endothelial cells (EA.hy926). Tube formation assays were performed to assess angiogenesis, and gene/protein expression analyses were conducted to evaluate HRG’s effects on integrins αV and β8. The role of nuclear factor erythroid 2-related factor 2 (NRF2) in HRG-mediated antiangiogenic activity was also examined through nuclear translocation assays and NRF2 activation studies.<br> Results: At physiological concentrations, HRG effectively suppressed TNF-α-induced tube formation in vitro and downregulated TNF-α-induced expression of integrins αV and β8 at both the mRNA and protein levels. HRG treatment promoted NRF2 nuclear translocation in a time-dependent manner. Furthermore, activation of NRF2 significantly reduced TNF-α-induced tube formation and integrin expression, suggesting that NRF2 plays a key role in HRG-mediated antiangiogenic effects.<br> Discussion and Conclusion: Our findings indicate that HRG suppresses TNF-α-induced angiogenesis by promoting NRF2 nuclear translocation and transcriptional activation, which in turn inhibits integrin αV and β8 expression. Given the essential role of angiogenesis in tumor progression, HRG’s ability to regulate this process presents a promising therapeutic strategy for cancer treatment. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2666-3341 6 S1 2025 Basic biology is not just “for the birds”: how avian studies have informed us about vertebrate reproduction 7 12 EN George E. Bentley Department of Integrative Biology and Helen Wills Neuroscience Institute, University of California at Berkeley Sayaka Aizawa Graduate School of Natural Science and Technology, Okayama University Avian reproductive physiology has been studied for centuries, largely because of the importance of birds as food animals. It is likely that the ubiquity and ease of access to domesticated chickens led to them being used in some of the first experiments on transplantation of endocrine structures—in this case, the testes. Since then, study of seasonal changes in reproductive physiology (photoperiodism) in different orders of bird species has led to advances in the understanding of endocrine regulation of reproductive physiology and behavior. These include mechanisms of adult neuroplasticity, sexual selection, sperm competition, stress physiology, and circadian physiology. Here, we focus mainly on the discovery in birds of a neuropeptide named gonadotropin-inhibitory hormone that mostly has inhibitory effects on reproduction. This hormone has since been shown to exist in all mammals studied to date, including humans (it is known as RFamide-related peptide in mammals). We discuss the history and implications of avian studies on gonadotropin-inhibitory hormone/RFamide-related peptide for human reproductive biology. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1867-1071 43 8 2025 Overview of task shifting guidelines in Japan: from radiologists to radiological technologists 1261 1268 EN Aki Kido Department of Radiology, Toyama University Hospital Kazuko Ohno Department of Radiological Technology, Kyoto University of Medial Science Kei Yamada Department of Radiology, Kyoto Prefectural University of Medicine Koichiro Yamakado Department of Radiology, The Hospital of Hyogo College of Medicine Takao Hiraki Department of Radiology, Okayama University Takashi Mizowaki Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University Noriko Aida Department of Diagnostic Radiology, Yokohama City University Graduate School of Medicine Noriko Oyama-Manabe Department of Radiology, Jichi Medical University Saitama Medical Center Naoki Kodama Department of Radiological Technology, Faculty of Medical Technology, Niigata University of Health and Welfare Katsuhiko Ueda Department of Radiological Sciences, School of Health Sciences at Narita, International University of Health and Welfare Shigeki Aoki Health Data Science, Department of Radiology/Data Science, Graduate School of Medicine, Juntendo University Noriyuki Tomiyama Department of Radiology, Osaka University Graduate School of Medicine As one of the key pillars of work style reform for physicians, task shifting and sharing from radiologists to radiological technologists has been considered. In May 2021, the Radiological Technologists Act was amended, allowing for the expansion of several duties. Alongside these legal and regulatory changes, a notice from Ministry of Health, Labour and Welfare was issued, highlighting tasks to be particularly promoted under the current system prior to the amendment of the Radiological Technologists Act. These amendments authorize radiological technologists to perform advanced and specialized tasks, such as securing venous access for contrast agent administration, which require significantly higher skill levels than their traditional roles. However, the amended legislation did not include specific guidelines, rules, or considerations for the practical implementation of these new duties in daily medical practice, especially from the perspectives of patient safety and quality of care. To address this, the Japan Radiological Society, the Japanese College of Radiology, and the Japan Association of Radiological Technologists collaborated with other related societies to develop guidelines on five key topics:-Guidelines for Safe Conduct of CT/MRI Contrast-Enhanced Examinations: Considering the expanded scope of practice for radiological technologists. -Guidelines for Safe Conduct of Nuclear Medicine Examinations: Aligned with the expanded responsibilities of radiological technologists. -Guidelines for Clinical application of Image-Guided Radiation Therapy (IGRT). -Guidelines for Safe Conduct of Angiography and Interventional Radiology (IR): Adapted for the expanded roles of radiological technologists. -Guidelines for Reporting Findings of STAT Imaging: Addressing urgent conditions with potential impact on life prognosis. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0360-3199 140 2025 Advances in filler-crosslinked membranes for hydrogen fuel cells in sustainable energy generation 745 776 EN Aminul Islam Department of Petroleum and Mining Engineering, Jashore University of Science and Technology Mamun Shahriar Department of Petroleum and Mining Engineering, Jashore University of Science and Technology Md. Tarekul Islam Department of Leather Engineering, Faculty of Mechanical Engineering, Khulna University of Engineering and Technology Siow Hwa Teo Industrial Chemistry Program, Faculty of Science and Natural Resources, Universiti Malaysia Sabah M. Azizur R. Khan Department of Chemistry, Jashore University of Science and Technology Yun Hin Taufiq-Yap Catalysis Science and Technology Research Centre, Faculty of Science, Universiti Putra Malaysia Suman C. Mohanta Department of Chemistry, Jashore University of Science and Technology Ariyan Islam Rehan Department of Chemistry, School of Science, The University of Tokyo Adiba Islam Rasee Department of Chemistry, Graduate School of Science, Osaka University Khadiza Tul Kubra Department of Chemistry, Graduate School of Science, Osaka University Md. Munjur Hasan Department of Chemistry, Graduate School of Science, Osaka University Md. Shad Salman Institute for Chemical Research, Kyoto University R.M. Waliullah Institute for Chemical Research, Kyoto University Md. Nazmul Hasan Department of Chemistry, School of Science, The University of Tokyo Md. Chanmiya Sheikh Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Tetsuya Uchida Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Mrs Eti Awual Institute for Chemical Research, Kyoto University Mohammed Sohrab Hossain Department of Chemistry, Graduate School of Science, Osaka University Hussein Znad Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University Md. Rabiul Awual Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University Fuel cell membranes can be used in various ways to achieve zero-emission transport and energy systems, which offer a promising way to power production due to their higher efficiency compared to the internal combustion engine and the eco-environment. Perfluoro sulfonic acid membranes used for proton exchange membranes (PEMs) have certain drawbacks, like higher fuel permeability and expense, lower mechanical and chemical durability, and proton conductivity under low humidity and above 80 °C temperature. Researchers have drawn their attention to the production of polymer electrolyte membranes with higher proton conductivity, thermal and chemical resilience, maximum power density, lower fuel permeability, and lower expense. For sustainable clean energy generation, a review covering the most useful features of advanced material-associated membranes would be of great benefit to all interested communities. This paper endeavors to explore several types of novel inorganic fillers and crosslinking agents, which have been incorporated into membrane matrices to design the desired properties for an advanced fuel cell system. Membrane parameters such as proton conductivity, the ability of H2 transport, and the stability of the membrane are described. Research directions for developing fuel cell membranes are addressed based on several challenges suggested. The technological advancement of nanostructured materials for fuel cell applications is believed to significantly promote the future clean energy generation technology in practice. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0360-3199 101 2025 Next frontier in photocatalytic hydrogen production through CdS heterojunctions 173 211 EN Aminul Islam Department of Petroleum and Mining Engineering, Jashore University of Science and Technology Abdul Malek Department of Petroleum and Mining Engineering, Jashore University of Science and Technology Md. Tarekul Islam Department of Leather Engineering, Faculty of Mechanical Engineering, Khulna University of Engineering and Technology Farzana Yeasmin Nipa Department of Petroleum and Mining Engineering, Jashore University of Science and Technology Obayed Raihan Department of Pharmaceutical Sciences, College of Health Sciences and Pharmacy, Chicago State University Hasan Mahmud Bangladesh Energy and Power Research Council (BEPRC) Md. Elias Uddin Department of Leather Engineering, Faculty of Mechanical Engineering, Khulna University of Engineering and Technology Mohd Lokman Ibrahim School of Chemistry and Environment, Faculty of Applied Sciences, Universiti Teknologi MARA G. Abdulkareem-Alsultan Catalysis Science and Technology Research Centre, Faculty of Science, Universiti Putra Malaysia Alam Hossain Mondal USAID - Bangladesh Advancing Development and Growth through Energy (BADGE) Project, Tetra Tech Md. Munjur Hasan Department of Chemistry, Graduate School of Science, Osaka University Md. Shad Salman Institute for Chemical Research, Kyoto University Khadiza Tul Kubra Department of Chemistry, Graduate School of Science, Osaka University Md. Nazmul Hasan Department of Chemistry, School of Science, The University of Tokyo Md. Chanmiya Sheikh Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Tetsuya Uchida Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Adiba Islam Rasee Department of Chemistry, Graduate School of Science, Osaka University Ariyan Islam Rehan Department of Chemistry, School of Science, The University of Tokyo Mrs Eti Awual Institute for Chemical Research, Kyoto University Mohammed Sohrab Hossain Department of Chemistry, Graduate School of Science, Osaka University R.M. Waliullah Institute for Chemical Research, Kyoto University Md. Rabiul Awual Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University Photocatalytic hydrogen (H₂) generation via solar-powered water splitting represents a sustainable solution to the global energy crisis. Cadmium sulfide (CdS) has emerged as a promising semiconductor photocatalyst due to its tunable bandgap, high physicochemical stability, cost-effectiveness, and widespread availability. This review systematically examines recent advancements in CdS-based heterojunctions, categorized into CdS-metal (Schottky), CdS-semiconductor (p-n, Z-scheme, S-scheme), and CdS-carbon heterojunctions. Various strategies employed to enhance photocatalytic efficiency and stability are discussed, including band structure engineering, surface modification, and the incorporation of crosslinked architectures. A critical evaluation of the underlying photocatalytic mechanisms highlights recent efforts to improve charge separation and photostability under operational conditions. This review highlights the challenges and opportunities in advancing CdS-based photocatalysts and provides a direction for future research. The insights presented aim to accelerate the development of efficient and durable CdS-based photocatalysts for sustainable H₂ production. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1438-4957 2025 From sewage sludge to agriculture: governmental initiatives, technologies, and sustainable practices in Japan EN Thu Huong Nguyen Graduate School of Engineering, Kyoto University Taku Fujiwara Graduate School of Engineering, Kyoto University Hiromasa Yamashita Water Supply and Sewerage Department, National Institute for Land and Infrastructure Management Hironori Togawa Water Supply and Sewerage Department, National Institute for Land and Infrastructure Management Haruo Miyake R & D Department, Japan Sewage Works Agency Masako Goto 1St Research Department, Japan Institute of Wastewater Engineering and Technology Hideaki Nagare Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Masato Nakamura Institute for Rural Engineering, NARO Fumiko Oritate Institute for Rural Engineering, NARO Hirotaka Ihara Institute for Agro-Environmental Sciences, NARO Morihiro Maeda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sewage sludge (SS), an underutilized but valuable resource for agriculture, contains essential nutrients, such as phosphorus. In Japan, where dependence on imported fertilizers is high and global price fluctuations persist, using SS as fertilizer presents a sustainable alternative aligned with circular economy goals. This review analyzes Japan’s current efforts to repurpose SS, focusing on technological developments and key policy initiatives that promote safe and effective application. Selective phosphorus recovery technologies mitigate resource depletion, while holistic approaches, such as composting and carbonization, maximize sludge utilization for agricultural applications. Government-led initiatives, including public awareness campaigns, quality assurance standards and research support, have facilitated the adoption of sludge-based fertilizers. To contextualize Japan’s position, international trends, particularly in the EU, are also examined. These comparisons reveal both common strategies and areas for policy and technological advancement, especially regarding regulation of emerging contaminants. By integrating national case studies with global perspectives, the study offers insights into the economic, environmental, and social benefits of SS reuse, contributing to Japan’s goals of resource self-sufficiency and carbon neutrality, while also informing broader sustainable agriculture transitions worldwide. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0001-8686 343 2025 Progress in silicon-based materials for emerging solar-powered green hydrogen (H2) production 103558 EN Aminul Islam Department of Petroleum and Mining Engineering, Jashore University of Science and Technology Md. Tarekul Islam Department of Leather Engineering, Faculty of Mechanical Engineering, Khulna University of Engineering and Technology Siow Hwa Teo Industrial Chemistry Program, Faculty of Science and Natural Resources, Universiti Malaysia Sabah Hasan Mahmud Bangladesh Energy and Power Research Council (BEPRC) A.M. Swaraz Department of Genetic Engineering and Biotechnology, Jashore University of Science and Technology Ariyan Islam Rehan Department of Chemistry, School of Science, The University of Tokyo Adiba Islam Rasee Department of Chemistry, Graduate School of Science, Osaka University Khadiza Tul Kubra Department of Chemistry, Graduate School of Science, Osaka University Md. Munjur Hasan Department of Chemistry, Graduate School of Science, Osaka University Md. Shad Salman Institute for Chemical Research, Kyoto University R.M. Waliullah Institute for Chemical Research, Kyoto University Md. Nazmul Hasan Department of Chemistry, School of Science, The University of Tokyo Md. Chanmiya Sheikh Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Tetsuya Uchida Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Mrs Eti Awual Department of Chemistry, Graduate School of Science, Osaka University Mohammed Sohrab Hossain Department of Chemistry, Graduate School of Science, Osaka University Hussein Znad Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University Md. Rabiul Awual Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University The imperative demand for sustainable and renewable energy solutions has precipitated profound scientific investigations into photocatalysts designed for the processes of water splitting and hydrogen fuel generation. The abundance, low toxicity, high conductivity, and cost-effectiveness of silicon-based compounds make them attractive candidates for hydrogen production, driving ongoing research and technological advancements. Developing an effective synthesis method that is simple, economically feasible, and environmentally friendly is crucial for the widespread implementation of silicon-based heterojunctions for sustainable hydrogen production. Balancing the performance benefits with the economic and environmental considerations is a key challenge in the development of these systems. The specific performance of each catalyst type can vary depending on the synthesis method, surface modifications, catalyst loading, and reaction conditions. The confluence of high crystallinity, reduced oxygen concentration, and calcination temperature within the silicon nanoparticle has significantly contributed to its noteworthy hydrogen evolution rate. This review provides an up-to-date evaluation of Si-based photocatalysts, summarizing recent developments, guiding future research directions, and identifying areas that require further investigation. By combining theoretical insights and experimental findings, this review offers a comprehensive understanding of Si-based photocatalysts for water splitting. Through a comprehensive analysis, it aims to elucidate existing knowledge gaps and inspire future research directions towards optimized photocatalytic performance and scalability, ultimately contributing to the realization of sustainable hydrogen generation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2041-1723 15 1 2024 Neurotransmitter recognition by human vesicular monoamine transporter 2 7661 EN Dohyun Im Department of Cell Biology, Graduate School of Medicine, Kyoto University Mika Jormakka Department of Cell Biology, Graduate School of Medicine, Kyoto University Narinobu Juge Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University Jun-ichi Kishikawa Department of Applied Biology, Kyoto Institute of Technology Takayuki Kato Institute for Protein Research, Osaka University Yukihiko Sugita Laboratory of Ultrastructural Virology, Institute for Life and Medical Sciences, Kyoto University Takeshi Noda Laboratory of Ultrastructural Virology, Institute for Life and Medical Sciences, Kyoto University Tomoko Uemura Department of Cell Biology, Graduate School of Medicine, Kyoto University Yuki Shiimura Department of Cell Biology, Graduate School of Medicine, Kyoto University Takaaki Miyaji Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University Hidetsugu Asada Department of Cell Biology, Graduate School of Medicine, Kyoto University So Iwata Department of Cell Biology, Graduate School of Medicine, Kyoto University Human vesicular monoamine transporter 2 (VMAT2), a member of the SLC18 family, plays a crucial role in regulating neurotransmitters in the brain by facilitating their uptake and storage within vesicles, preparing them for exocytotic release. Because of its central role in neurotransmitter signalling and neuroprotection, VMAT2 is a target for neurodegenerative diseases and movement disorders, with its inhibitor being used as therapeutics. Despite the importance of VMAT2 in pharmacophysiology, the molecular basis of VMAT2-mediated neurotransmitter transport and its inhibition remains unclear. Here we show the cryo-electron microscopy structure of VMAT2 in the substrate-free state, in complex with the neurotransmitter dopamine, and in complex with the inhibitor tetrabenazine. In addition to these structural determinations, monoamine uptake assays, mutational studies, and pKa value predictions were performed to characterize the dynamic changes in VMAT2 structure. These results provide a structural basis for understanding VMAT2-mediated vesicular transport of neurotransmitters and a platform for modulation of current inhibitor design. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2053-3624 12 1 2025 Clinical impact of combined assessment of myocardial inflammation and fibrosis using myocardial biopsy in patients with dilated cardiomyopathy: a multicentre, retrospective cohort study e003250 EN Takafumi Nakayama Department of Cardiology, Nagoya City University Graduate School of Medical Sciences Keiko Ohta Ogo Department of Pathology, National Cerebral and Cardiovascular Center Yasuo Sugano Department of Cardiology, Keiyu Hospital Tetsuro Yokokawa Department of Cardiovascular Medicine, Fukushima Medical University Hiromitsu Kanamori Department of Cardiology, Gifu University Graduate School of Medicine Yoshihiko Ikeda Department of Pathology, National Cerebral and Cardiovascular Center Michiaki Hiroe Department of Cardiology, National Center for Global Health and Medicine Kinta Hatakeyama Department of Pathology, National Cerebral and Cardiovascular Center Hatsue Ishibashi-Ueda Department of Pathology, National Cerebral and Cardiovascular Center Kazufumi Nakamura Center for Advanced Heart Failure, Okayama University Hospital Kaoru Dohi Department of Cardiology and Nephrology, Mie University Graduate School of Medicine Toshihisa Anzai Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine Yoshihiro Seo Department of Cardiology, Nagoya City University Graduate School of Medical Sciences Kyoko Imanaka-Yoshida Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine Background Among patients with dilated cardiomyopathy (DCM), myocardial inflammation and fibrosis are risk factors for poor clinical outcomes. Here, we investigated the combined prognostic value of these two factors, as evaluated using myocardial biopsy samples.<br> Methods This retrospective and multicentre study included patients with DCM—defined as LVEF of ≤45% and left diastolic diameter of >112% of predicted value, without evidence of secondary or ischaemic cardiomyopathy. In myocardial biopsy samples, inflammatory cells were counted using immunohistochemistry, and Masson’s Trichrome staining was performed to quantify the myocardial fibrosis as collagen area fraction (CAF). Higher myocardial inflammation was defined as leucocytes of ≥14/mm², including ≤4 monocytes/mm², with CD3+ T lymphocytes of≥7/mm². Greater myocardial fibrosis was defined as CAF of>5.9% by the Youden’s index. The primary endpoint was cardiac death or left ventricular assist device implantation.<br> Results A total of 255 DCM patients were enrolled (average age, 53.1 years; 78% males). Within this cohort, the mean LVEF was 28.0%, mean CAF was 10.7% and median CD3+ cell count was 8.3/mm2. During the median follow-up period of 2688 days, 46 patients met the primary endpoint. Multivariable Cox proportional hazard analyses revealed that CD3+ cell count and CAF were independent determinants of the primary endpoint. Kaplan–Meier analysis showed that patients with both higher myocardial inflammation and greater fibrosis had the worst prognosis (log-rank p<0.001). When myocardial inflammation was graded as one of three degrees: T lymphocytes of <13/mm² (low); 13 of 13.1–23.9/mm² (moderate); and T lymphocytes of ≥24 /mm² (high), patients with moderate inflammation exhibited a superior survival rate when CAF was ≤5.9%, but a worse survival rate when CAF was >5.9%.<br> Conclusions Having both biopsy-proven higher myocardial inflammation and greater fibrosis predicted the worst clinical prognosis in patients with DCM. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2691-3704 5 2 2025 Mechanistic Insights Into Oxidative Response of Heat Shock Factor 1 Condensates 606 617 EN Soichiro Kawagoe Institute of Advanced Medical Sciences, Tokushima University Motonori Matsusaki Institute of Advanced Medical Sciences, Tokushima University Takuya Mabuchi Frontier Research Institute for Interdisciplinary Sciences, Tohoku University Yuto Ogasawara Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kazunori Watanabe Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Koichiro Ishimori Department of Chemistry, Faculty of Science, Hokkaido University Tomohide Saio Institute of Advanced Medical Sciences, Tokushima University Heat shock factor 1 (Hsf1), a hub protein in the stress response and cell fate decisions, senses the strength, type, and duration of stress to balance cell survival and death through an unknown mechanism. Recently, changes in the physical property of Hsf1 condensates due to persistent stress have been suggested to trigger apoptosis, highlighting the importance of biological phase separation and transition in cell fate decisions. In this study, the mechanism underlying Hsf1 droplet formation and oxidative response was investigated through 3D refractive index imaging of the internal architecture, corroborated by molecular dynamics simulations and biophysical/biochemical experiments. We found that, in response to oxidative conditions, Hsf1 formed liquid condensates that suppressed its internal mobility. Furthermore, these conditions triggered the hyper-oligomerization of Hsf1, mediated by disulfide bonds and secondary structure stabilization, leading to the formation of dense core particles in the Hsf1 droplet. Collectively, these data demonstrate how the physical property of Hsf1 condensates undergoes an oxidative transition by sensing redox conditions to potentially drive cell fate decisions. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0169-5002 207 2025 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 108683 EN Anne-Marie C. Dingemans Erasmus MC Cancer Institute, University Medical Center Konstantinos Syrigos Sotiria General Hospital Lorenzo Livi Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, University of Florence Astrid Paulus Centre Hospitalier Universitaire de Liège Sang-We Kim Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine Yuanbin Chen The Cancer & Hematology Centers of Western Michigan Enriqueta Felip Medical Oncology Department, Vall d’Hebron University Hospital Frank Griesinger Pius-Hospital Oldenburg Kadoaki Ohashi Okayama University Hospital Gerard Zalcman Hospital Bichat-Claude Bernard Brett G.M. Hughes The Prince Charles Hospital, University of Queensland Jens Benn Sørensen Rigshospitalet Normand Blais Department of Medicine, Centre Hospitalier de l’Université de Montréal Carlos G.M. Ferreira Oncoclinicas Colin R. Lindsay Division of Cancer Sciences, University of Manchester and The Christie NHS Foundation Trust Rafal Dziadziuszko University Clinical Centre, Medical University of Gdansk Patrick J. Ward SCRI at OHC Cynthia Chinedu Obiozor Amgen Inc. Yang Wang Amgen Inc. Solange Peters Lausanne University Hospital 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).<br> 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.<br> 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.<br> 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.<br> Clinical trials registration number: NCT04303780. No potential conflict of interest relevant to this article was reported.

Korean Association for the Study of Intestinal Diseases Acta Medica Okayama 1598-9100 2025 Week 2 remission with vedolizumab as a predictor of long-term remission in patients with ulcerative colitis: a multicenter, retrospective, observational study EN Taku Kobayashi Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital Tadakazu Hisamatsu Department of Gastroenterology and Hepatology, Kyorin University School of Medicine Satoshi Motoya Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital Toshimitsu Fujii Department of Gastroenterology and Hepatology, Institute of Science Tokyo Reiko Kunisaki Inflammatory Bowel Disease Center, Yokohama City University Medical Center Tomoyoshi Shibuya Department of Gastroenterology, Juntendo University School of Medicine Minoru Matsuura Department of Gastroenterology and Hepatology, Kyorin University School of Medicine Ken Takeuchi Department of Gastroenterology and Hepatology, IBD Center, Tsujinaka Hospital Kashiwanoha Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Hospital Hiroshi Yasuda Department of Gastroenterology, St. Marianna University School of Medicine Kaoru Yokoyama Department of Gastroenterology, Kitasato University School of Medicine Noritaka Takatsu Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital Atsuo Maemoto Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital Toshiyuki Tahara Department of Gastroenterology, Saiseikai Utsunomiya Hospital Keiichi Tominaga Department of Gastroenterology, Dokkyo Medical University Masaaki Shimada Department of Gastroenterology, NHO Nagoya Medical Center Nobuaki Kuno Department of Gastroenterology and Medicine, Fukuoka University Hospital Mary Cavaliere Japan Medical Office, Takeda Pharmaceutical Company Limited Kaori Ishiguro Japan Medical Office, Takeda Pharmaceutical Company Limited Jovelle L Fernandez Japan Medical Office, Takeda Pharmaceutical Company Limited Toshifumi Hibi Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital Background/Aims Vedolizumab (VDZ), a gut-selective monoclonal antibody for ulcerative colitis (UC) treatment, has no established biomarkers or clinical features that predict long-term remission. Week 2 remission, a potential predictor of long-term remission, could inform maintenance treatment strategy.<br> Methods This retrospective, observational chart review included patients with UC in Japan who initiated VDZ between December 2018 and February 2020. Outcome measures included 14- and 54-week remission rates in patients with week 2 and non-week 2 remission (remission by week 14), 54-week remission rates in patients with week 14 remission and primary nonresponse, and predictive factors of week 2 and week 54 remission (logistic regression).<br> Results Overall, 332 patients with UC (176 biologic-naïve and 156 biologic-non-naïve) were included. Significantly more biologic-naïve than biologic-non-naïve patients achieved week 2 remission (36.9% vs. 28.2%; odds ratio [OR], 1.43; 95% confidence interval [CI], 1.05–1.94; P=0.0224). Week 54 remission rates were significantly different between week 14 remission and primary nonresponse (both groups: P<0.0001), and between week 2 and non-week 2 remission (all patients: OR, 2.41; 95% CI, 1.30–4.48; P=0.0052; biologic-naïve patients: OR, 2.40; 95% CI, 1.10–5.24; P=0.0280). Week 2 remission predictors were male sex, no anti-tumor necrosis factor alpha exposure, and normal/mild endoscopic findings. Week 54 remission was significantly associated with week 2 remission and no tacrolimus use.<br> Conclusions Week 2 remission with VDZ is a predictor of week 54 remission in patients with UC. Week 2 may be used as an evaluation point for UC treatment decisions. (Japanese Registry of Clinical Trials: jRCT-1080225363) No potential conflict of interest relevant to this article was reported.

Korean Association for the Study of Intestinal Diseases Acta Medica Okayama 1598-9100 2025 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 Taku Kobayashi Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital Tadakazu Hisamatsu Department of Gastroenterology and Hepatology, Kyorin University School of Medicine Satoshi Motoya Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital Minoru Matsuura Department of Gastroenterology and Hepatology, Kyorin University School of Medicine Toshimitsu Fujii Department of Gastroenterology and Hepatology, Institute of Science Tokyo Reiko Kunisaki Inflammatory Bowel Disease Center, Yokohama City University Medical Center Tomoyoshi Shibuya Department of Gastroenterology, Juntendo University School of Medicine Ken Takeuchi Department of Gastroenterology and Hepatology, IBD Center, Tsujinaka Hospital Kashiwanoha Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Hospital Hiroshi Yasuda Department of Gastroenterology, St. Marianna University School of Medicine Kaoru Yokoyama Department of Gastroenterology, Kitasato University School of Medicine Noritaka Takatsu Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital Atsuo Maemoto Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital Toshiyuki Tahara Department of Gastroenterology, Saiseikai Utsunomiya Hospital Keiichi Tominaga Department of Gastroenterology, Dokkyo Medical University Masaaki Shimada Department of Gastroenterology, NHO Nagoya Medical Center Nobuaki Kuno Department of Gastroenterology and Medicine, Fukuoka University Hospital Mary Cavaliere Japan Medical Office, Takeda Pharmaceutical Company Limited Kaori Ishiguro Japan Medical Office, Takeda Pharmaceutical Company Limited Jovelle L Fernandez Japan Medical Office, Takeda Pharmaceutical Company Limited Toshifumi Hibi Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital 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.<br> 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.<br> 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).<br> 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) No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0815-9319 40 6 2025 Real-World Effectiveness and Safety of Vedolizumab in Patients ≥ 70 Versus < 70 Years With Ulcerative Colitis: Multicenter Retrospective Study 1435 1445 EN Tadakazu Hisamatsu Department of Gastroenterology and Hepatology, Kyorin University School of Medicine Taku Kobayashi Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital Satoshi Motoya Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital Toshimitsu Fujii Department of Gastroenterology and Hepatology, Institute of Science Tokyo Reiko Kunisaki Inflammatory Bowel Disease Center, Yokohama City University Medical Center Tomoyoshi Shibuya Department of Gastroenterology, Juntendo University School of Medicine Minoru Matsuura Department of Gastroenterology and Hepatology, Kyorin University School of Medicine Sakiko Hiraoka Ken Takeuchi Department of Gastroenterology and Hepatology, IBD Center, Tsujinaka Hospital Kashiwanoha Hiroshi Yasuda Department of Gastroenterology, St. Marianna University School of Medicine Kaoru Yokoyama Department of Gastroenterology, Kitasato University School of Medicine Noritaka Takatsu Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital Atsuo Maemoto Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital Toshiyuki Tahara Department of Gastroenterology, Saiseikai Utsunomiya Hospital Keiichi Tominaga Department of Gastroenterology, Dokkyo Medical University Masaaki Shimada Department of Gastroenterology, NHO Nagoya Medical Center Nobuaki Kuno Department of Gastroenterology and Medicine, Fukuoka University Hospital Jovelle L. Fernandez Japan Medical Office, Takeda Pharmaceutical Company Limited Lisa Hirose Japan Medical Office, Takeda Pharmaceutical Company Limited Kaori Ishiguro Japan Medical Office, Takeda Pharmaceutical Company Limited Mary Cavaliere Japan Medical Office, Takeda Pharmaceutical Company Limited Toshifumi Hibi Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital 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.<br> 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]).<br> 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.<br> 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.<br> Trial Registration: Japanese Registry of Clinical Trials registration number: jRCT-1080225363 No potential conflict of interest relevant to this article was reported.

Korean Association for the Study of Intestinal Diseases Acta Medica Okayama 1598-9100 2025 Factors affecting 1-year persistence with vedolizumab for ulcerative colitis: a multicenter, retrospective real-world study EN Taku Kobayashi Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital Tadakazu Hisamatsu Department of Gastroenterology and Hepatology, Kyorin University School of Medicine Satoshi Motoya Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital Toshimitsu Fujii Department of Gastroenterology and Hepatology, Institute of Science Tokyo Reiko Kunisaki Inflammatory Bowel Disease Center, Yokohama City University Medical Center Tomoyoshi Shibuya Department of Gastroenterology, Juntendo University School of Medicine Minoru Matsuura Department of Gastroenterology and Hepatology, Kyorin University School of Medicine Ken Takeuchi Department of Gastroenterology and Hepatology, IBD Center Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Hospital Hiroshi Yasuda Department of Gastroenterology, St. Marianna University School of Medicine Kaoru Yokoyama Department of Gastroenterology, Kitasato University School of Medicine Noritaka Takatsu Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital Atsuo Maemoto Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital Toshiyuki Tahara Department of Gastroenterology, Saiseikai Utsunomiya Hospital Keiichi Tominaga Department of Gastroenterology, Dokkyo Medical University Masaaki Shimada Department of Gastroenterology, NHO Nagoya Medical Center Nobuaki Kuno Department of Gastroenterology and Medicine, Fukuoka University Hospital Jovelle L. Fernandez Japan Medical Office, Takeda Pharmaceutical Company Limited Kaori Ishiguro Japan Medical Office, Takeda Pharmaceutical Company Limited Mary Cavaliere Japan Medical Office, Takeda Pharmaceutical Company Limited Hisato Deguchi Japan Medical Office, Takeda Pharmaceutical Company Limited Toshifumi Hibi Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital 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.<br> 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.<br> 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.<br> Conclusions Persistence with vedolizumab was consistent with previous reports. Use of tacrolimus and shorter disease duration were the main predictors of decreased persistence. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1434-3916 145 1 2024 Medial meniscus posterior root tears with advanced osteoarthritis or subchondral insufficiency fracture are good indications for unicompartmental knee arthroplasty at a minimum 2-year follow-up 64 EN Koki Kawada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yusuke Yokoyama Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masanori Tamura Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Introduction The outcomes of unicompartmental knee arthroplasty (UKA) in the presence and absence of medial meniscus posterior root tears (MMPRTs) have not been compared. This study compared the characteristics and clinical outcomes of patients undergoing UKA with and without MMPRTs.<br> Materials and methods This study analyzed 68 patients. The presence or absence of MMPRTs was evaluated using preoperative magnetic resonance imaging. Patient characteristics, clinical scores before surgery and at the final evaluation, and imaging findings were compared between patients with and without MMPRTs. Multiple regression analysis was conducted on postoperative visual analog scale (VAS)-pain scores.<br> Results MMPRTs were present in 64.7% (44/68) of patients. Patients with MMPRTs were significantly younger (67.8 ± 8.2 vs. 75.0 ± 7.1 years, p < 0.001) and had a shorter duration from the development of symptoms to the time of surgery than those without (6.8 ± 8.4 vs. 36.1 ± 38.9 months, p < 0.001). Component placement or lower-limb alignment did not significantly differ between the groups. Preoperative clinical scores were not significantly different between the groups; however, patients with MMPRTs showed significantly better postoperative VAS-pain scores than those without (10.0 ± 9.0 vs. 28.2 ± 26.0 points, p = 0.026). Multiple regression analysis of postoperative VAS-pain scores revealed the significant effect of duration from the development of symptoms to the time of surgery (p = 0.038).<br> Conclusions Patients undergoing UKA with MMPRTs were younger with less radiographic osteoarthritic changes compared to those without MMPRTs, and their postoperative VAS-pain scores were significantly superior. The duration from the development of symptoms to the time of surgery significantly influenced postoperative pain in patients undergoing UKA. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2045-7634 14 15 2025 Real‐World Data of Comprehensive Cancer Genomic Profiling Tests Performed in the Routine Clinical Setting in Sarcoma e71098 EN Eiji Nakata Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tatsunori Osone Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takuto Itano Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyuki Kunisada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naoyuki Ida Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hideki Yamamoto Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mashu Futagawa Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tatsunori Shimoi Department of Medical Oncology, National Cancer Center Hospital Hiroyuki Yanai Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akira Hirasawa Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinichi Toyooka Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masahiro Tabata Center for Clinical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 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.<br> 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.<br> 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.<br> 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. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0944-1174 2025 Distinct age-related effects of homologous recombination deficiency on genomic profiling and treatment efficacy in gastric cancer EN Yoshie Maki Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiyasu Kono Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Toshiki Ozato Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Hideki Yamamoto Department of Clinical Genomic Medicine, Okayama University Hospital Akira Hirasawa Department of Clinical Genomic Medicine, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Shinichi Toyooka Center for Comprehensive Genomic Medicine, Okayama University Hospital Kenta Hamada Faculty of Medicine, Department of Practical Gastrointestinal Endoscopy, Dentistry and Pharmaceutical Sciences, Okayama University Masaya Iwamuro Department of Gastroenterology, Okayama University Hospital Seiji Kawano Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Motoyuki Otsuka Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Background The incidence of gastric cancer among younger patients is increasing globally, with growing attention being paid to the role of homologous recombination deficiency (HRD). However, the effect of HRD on treatment outcomes and prognosis in this population remains unclear.<br> Methods We analyzed clinical and genomic data from the Center for Cancer Genomics and Advanced Therapeutics database. Younger patients (≤ 39 years, n = 140) were compared with older patients (≥ 65 years, n = 1118) diagnosed with gastric cancer. This study focused on mutations in homologous recombination repair (HRR) genes and their association with tumor mutation burden (TMB), microsatellite instability (MSI), and treatment outcomes.<br> Results In older patients, HRD was associated with higher TMB and microsatellite instability-high (MSI-H) status, whereas no such correlations were observed in younger patients. Notably, MSI-H status was not observed in the younger group. Younger patients with HRD had a significantly shorter time to treatment failure (TTF) and overall survival (OS) than those without HRD. Conversely, in older patients, there was no significant difference in TTF or OS based on HRD status.<br> Conclusion HRR gene mutations influence genomic profiling, TMB, and MSI differently depending on the age of gastric cancer onset, suggesting potential effects on treatment efficacy and prognosis. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0304-3800 508 2025 Enhanced aboveground biomass density estimation in Central Vietnamese forests 111242 EN Viet Hoang Ho Graduate School of Environmental and Life Science, Okayama University Hidenori Morita Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Felix Bachofer German Aerospace Center (DLR), Earth Observation Center Thanh Ha Ho University of Agriculture and Forestry, Hue University 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. No potential conflict of interest relevant to this article was reported.

XMLink Acta Medica Okayama 2005-7806 16 4 2024 A novel brief questionnaire using a face rating scale to assess dental anxiety and fear 244 254 EN Takuya Mino Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Aya Kimura-Ono Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Hikaru Arakawa Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Kana Tokumoto Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Yoko Kurosaki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Yoshizo Matsuka Department of Stomatognathic Function and Occlusal Reconstruction, Graduate School of Biomedical Sciences, Tokushima University Kenji Maekawa Department of Removable Prosthodontics and Occlusion, Osaka Dental University Takuo Kuboki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences PURPOSE This study aimed to evaluate the reliability and validity of a four-item questionnaire using a face rating scale to measure dental trait anxiety (DTA), dental trait fear (DTF), dental state anxiety (DSA), and dental state fear (DSF).<br> MATERIALS AND METHODS Participants were consecutively selected from patients undergoing scaling (S-group; n = 47) and implant placement (I-group; n = 25). The S-group completed the questionnaire both before initial and second scaling, whereas the I-group responded on the pre-surgery day (Pre-day), the day of implant placement (Imp-day), and the day of suture removal (Post-day).<br> RESULTS The reliability in the S-group was evaluated using the test-retest method, showing a weighted kappa value of DTA, 0.61; DTF, 0.46; DSA, 0.67; DSF, 0.52. Criterion-related validity, assessed using the State-Trait Anxiety Inventory’s trait anxiety and state anxiety, revealed positive correlations between trait anxiety and DTA/DTF (DTA, ρ = 0.30; DTF, ρ = 0.27, ρ: correlation coefficient) and between state anxiety and all four items (DTA, ρ = 0.41; DTF, ρ = 0.32; DSA, ρ = 0.25; DSF, ρ = 0.25). Known-group validity was assessed using the initial data and Imp-day data from the S-group and I-group, respectively, revealing significantly higher DSA and DSF scores in the I-group than in the S-group. Responsiveness was gauged using I-group data, showing significantly lower DSA and DSF scores on post-day compared to other days.<br> CONCLUSION The newly developed questionnaire has acceptable reliability and validity for clinical use, suggesting its usefulness for research on dental anxiety and fear and for providing patient-specific dental care. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 2025 Advances in liquid biopsy for bone and soft-tissue sarcomas EN Yilang Wang Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takanao Kurozumi Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Teruhiko Ando Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takahiko Ishimaru Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroya Kondo Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eiji Nakata Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyuki Kunisada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Bone and soft-tissue sarcomas are a heterogeneous group of malignant tumors originating from mesenchymal tissues, accounting for approximately 1% of adult solid malignancies and 20% of pediatric solid malignancies. While blood-based tumor markers are available in major types of cancers, evidence demonstrating useful circulating biomarkers is limited in bone and soft-tissue sarcomas. Despite the development of combined modality treatments, a significant proportion of sarcoma patients respond poorly to chemotherapy or radiotherapy, leading to local relapse or distant metastasis. However, imaging methods, such as X-ray, computed tomography, positron emission tomography, magnetic resonance imaging, and scintigraphy, are mostly used to detect or monitor tumor development. Liquid biopsy is an emerging minimally invasive diagnostic technique that detects tumor-derived molecules in body fluids, including circulating tumor cells, circulating tumor DNA (ctDNA), circulating tumor RNA (ctRNA), and circulating extracellular vesicles. This method offers new possibilities for early tumor detection, prognostic evaluation, and therapeutic monitoring and may serve as a benchmark for treatment modification. This review focuses on the current technological advances in liquid biopsy for bone and soft-tissue sarcoma and explores its potential role in guiding personalized treatments. If these modalities could determine resistance to ongoing therapy or the presence of minimal residual disease at the end of the treatment protocol, the obtained data would be important for determining whether to change treatment approaches or add adjuvant therapies. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 2379-5042 10 6 2025 Mycobacterium tuberculosis bacillus induces pyroptosis in human lung fibroblasts e00110-25 EN Takemasa Takii Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association Hiroyuki Yamada Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association Chihiro Motozono Department of Molecular Immunology, Research Institute for Microbial Diseases, The University of Osaka Sho Yamasaki Department of Molecular Immunology, Research Institute for Microbial Diseases, The University of Osaka Jordi B. Torrelles Texas Biomedical Research Institute and International Center for the Advancement of Research & Education (I•CARE) Joanne Turner Texas Biomedical Research Institute and International Center for the Advancement of Research & Education (I•CARE) Aoi Kimishima Laboratory of Applied Microbial Chemistry, Ōmura Satoshi Memorial Institute, Kitasato University Yukihiro Asami Laboratory of Applied Microbial Chemistry, Ōmura Satoshi Memorial Institute, Kitasato University Naoya Ohara Department of Oral Microbiology, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University Shigeaki Hida Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University Hidetoshi Hayashi Department of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University Kikuo Onozaki Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University 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. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1439-7595 35 4 2025 Telemedicine as an alternative to in-person care in the field of rheumatic diseases: A systematic scoping review 715 721 EN Ken-ei Sada Department of Clinical Epidemiology, Kochi Medical School Shigeru Iwata Department of Rheumatology and Clinical Immunology, Wakayama Medical University Yuzaburo Inoue Department of General Medical Science, Graduate School of Medicine, Chiba University Eiichi Tanaka Department of Rheumatology, Tokyo Women’s Medical University School of Medicine Keiichiro Nishida Locomotive Pain Center, Okayama University Hospital Yutaka Kawahito Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Asami Abe Department of Rheumatology, Niigata Rheumatic Center Atsushi Kawakami Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Takako Miyamae Department of Pediatric Rheumatology, Institute of Rheumatology, Tokyo Women’s Medical University 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.<br> 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.<br> 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.<br> 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. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0919-8172 32 1 2024 What is the identity of Gerota fascia? Histological study with cadavers 62 68 EN Yasuyuki Kobayashi Minimally Invasive Therapy Center, Okayama University Hospital Kohei Edamura Department of Urology, Okayama University Hospital Takuya Sadahira Department of Urology, Okayama University Hospital Yusuke Tominaga Department of Urology, Okayama University Hospital Satoshi Katayama Department of Urology, Okayama University Hospital Takehiro Iwata Department of Urology, Okayama University Hospital Shingo Nishimura Organ Transplant Center, Okayama University Hospital Tomoko Kobayashi Department of Urology, Okayama University Hospital Keita Sato Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaaki Komiyama Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryusuke Momota Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideyo Ohuchi Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objectives: The advancement of laparoscopic surgery has allowed surgeons to see finer anatomical structures during surgery. As a result, several issues have arisen regarding Gerota fascia that cannot be explained by previous interpretations, such as its various forms observed during surgery. To address these issues, we histologically examined the structure of Gerota fascia.<br> Methods: Specimens for study were prepared from kidneys with Gerota fascia from four cadavers, and the structure was studied histologically. Its thickness and collagen fiber area ratios were measured using ImageJ and compared to those of the epimysium of the rectus abdominis muscle.<br> Results: Connective tissue that appeared to be Gerota fascia was observed in 26 specimens. Histologically, the basic structure of Gerota fascia was a sandwich-like structure with a thin layer of thick, long collagen fibers in the central layer, and small granular collagen fibers scattered at the edges. However, not all areas observed had a similar structure; eight specimens were composed only of small granular collagen fibers. The average thickness of the Gerota fascia was 466 μm, and the area ratio of collagen was 27.1%. In contrast, the epimysium was much thicker than Gerota fascia, and its collagen fibers were much thicker and denser.<br> Conclusions: Gerota fascia, unlike the epimysium, was a very thin and fragile layer of collagen fibers, and its structure was diverse. This explains why Gerota fascia was observed in various states during surgery. It is important for surgeons to understand the properties of Gerota fascia and to treat it appropriately. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2637-6105 2025 Tailoring Mechanical Properties and Ionic Conductivity of Poly(ionic liquid)-Based Ion Gels by Tuning Anion Compositions EN Takaichi Watanabe Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Yuna Mizutani Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Carlos G. Lopez Material Science and Engineering Department, The Pennsylvania State University, 80 Pollock Road, State College Tsutomu Ono Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Poly(ionic liquid) (PIL)-based ion gels have emerged as promising materials for advanced electrochemical applications because of their excellent miscibility with ionic liquids (IL), tunable mechanical properties, and high ionic conductivity. Despite extensive studies on PIL-based ion gels, a comprehensive understanding of how different anion combinations in the system affect physicochemical properties is lacking. In this study, we systematically investigate the effect of different anion species, such as bis(trifluoromethanesulfonyl)imide (TFSI) and hexafluorophosphate (PF6), on the mechanical, viscoelastic, and ion conductive behaviors of PIL-based ion gels. We investigate the interplay between anion size, packing density, and polymer segmental dynamics by varying the anion composition in both the PIL network and IL component. Rheological analysis and uniaxial tensile testing results indicate that PF6-containing ion gels exhibit enhanced higher Young’s modulus because of their restricted chain mobility resulting in higher glass transition temperature (Tg). In addition, we confirm the anion exchange between PIL and IL during gel preparation and find that the mechanical and ion conductive properties of the gels are governed by the total molar ratio of anions in the gels. Our findings highlight that tuning the anion composition in PIL-based ion gels provides an effective strategy to tailor their performance, with potential applications for flexible electronics and solid-state electrochemical devices. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 63 24 2024 A Preliminary Survey of Rheumatologists on the Management of Late-onset Rheumatoid Arthritis in Japan 3299 3306 EN Satoshi Takanashi Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine Yuko Kaneko Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine Yutaka Kawahito Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Takashi Kida Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Takahiko Sugihara Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine Toshihisa Kojima National Hospital Organization Nagoya Medical Center, Orthopaedic Surgery and Rheumatology Ryozo Harada Department of Orthopaedic Surgery, Kurashiki Sweet Hospital Michinori Ishitoku Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital Shintaro Hirata Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital Motomu Hashimoto Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine Toshihiko Hidaka Miyazaki-Zenjinkai Hospital Asami Abe Department of Rheumatology, Niigata Rheumatic Center Hajime Ishikawa Department of Rheumatology, Niigata Rheumatic Center Hiromu Ito Kurashiki Central Hospital Mitsumasa Kishimoto Department of Nephrology and Rheumatology, Kyorin University School of Medicine Kazuo Matsui Department of Rheumatology, Teine Keijinkai Hospital Toshihiro Matsui Department of Rheumatology Research, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital Isao Matsushita Department of Rehabilitation Medicine, Kanazawa Medical University Akira Onishi Department of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto University Akio Morinobu Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University Keiichiro Nishida Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shuji Asai Department of Orthopaedic Surgery and Rheumatology, Nagoya University Graduate School of Medicine Eiichi Tanaka Division of Rheumatology, Department of Internal Medicine, Tokyo Women&apos;s Medical University School of Medicine Masayoshi Harigai Division of Rheumatology, Department of Internal Medicine, Tokyo Women&apos;s Medical University School of Medicine Masayo Kojima Department of Public Health, Nagoya City University Graduate School of Medical Sciences Objective We investigated the current perspectives regarding the management of late-onset rheumatoid arthritis (LORA) among rheumatologists in clinical practice.<br> Methods This study was performed in October 2021, and included 65 rheumatologists certified by the Japan College of Rheumatology, who were administered questionnaires (including multiple choice and descriptive formulae) regarding the management of LORA. We aggregated and analyzed the responses.<br> Results All 65 rheumatologists responded to the survey; 47 (72%) answered that >50% of newly diagnosed patients were aged ≥65 years, 42 (65%) answered that achievement of remission or low disease activity was the treatment goal, and 40 (62%) considered patient safety to be the highest priority. Most rheumatologists are concerned about the management of conditions other than RA, such as comorbidities, financial constraints, and life circumstances that interfere with standard or recommended treatment implementation.<br> Conclusion This preliminary survey highlighted various rheumatologists' perspectives regarding the management of LORA. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-3417 15 11 2025 Top-Down Stereolithography-Based System for Additive Manufacturing of Zirconia for Dental Applications 6155 EN Kumiko Yoshihara National Institute of Advanced Industrial Science and Technology (AIST), Health and Medical Research Institute Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Fiona Spirrett Joining and Welding Research Institute, Osaka University Yukinori Maruo Department of Prosthodontics, Okayama University Yasuhiro Yoshida Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Bart Van Meerbeek BIOMAT, Department of Oral Health Sciences, KU Leuven Soshu Kirihara Joining and Welding Research Institute, Osaka University This study investigated the feasibility and effectiveness of a commercial top-down stereolithography (SLA)-based system for the additive manufacturing of zirconia dental prostheses. Yttria-stabilized zirconia–resin slurries were prepared, and zirconia objects were fabricated using a top-down SLA system. Thermogravimetric–differential thermal analysis was used to examine the resin, while X-ray fluorescence spectroscopy and X-ray diffraction were used to analyze the printed samples. The microstructures of additively manufactured and subtractively manufactured zirconia were compared using field emission scanning electron microscopy (FE-SEM) before and after sintering. Biaxial flexural strength tests were also conducted to evaluate mechanical properties. The green bodies obtained via additive manufacturing exhibited uniform layering with strong interlayer adhesion. After sintering, the structures were dense with minimal porosity. However, compared to subtractively manufactured zirconia, the additively manufactured specimens showed slightly higher porosity and lower biaxial flexural strength. The results demonstrate the potential of SLA-based additive manufacturing for dental zirconia applications while also highlighting its current mechanical limitations. The study also showed that using a blade to evenly spread viscous slurry layers in a top-down SLA system can effectively reduce oxygen inhibition at the surface and relieve internal stresses during the layer-by-layer printing process, offering a promising direction for clinical adaptation. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 26 11 2025 Induced Pluripotent Stem Cells in Cardiomyopathy: Advancing Disease Modeling, Therapeutic Development, and Regenerative Therapy 4984 EN Quan Duy Vo Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukihiro Saito Department of Cardiovascular Medicine, Okayama University Hospital Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2490 25 1 2025 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 107 EN Ichiro Tsuboi Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Akihiro Matsukawa Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Mehdi Kardoust Parizi Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Marcin Miszczyk Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Tamás Fazekas Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Robert J Schulz Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Ekaterina Laukhtina Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Tatsushi Kawada Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Satoshi Katayama Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takehiro Iwata Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kensuke Bekku Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Pawel Rajwa Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Koichiro Wada Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Katharina Oberneder Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Piotr Chlosta Department of Urology, Medical College, Jagiellonian University Pierre I. Karakiewicz Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre Motoo Araki Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shahrokh F. Shariat Department of Urology, Comprehensive Cancer Center, Medical University of Vienna 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.<br> 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.<br> 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).<br> 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. No potential conflict of interest relevant to this article was reported.

Spandidos Publications Acta Medica Okayama 2754-3242 5 4 2025 Influence of tumor‑associated factors on the treatment selection between partial nephrectomy and ablation therapy for small renal tumors (Review) 48 EN Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shota Inoue Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kasumi Yoshinaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoaki Yamanoi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Mitsui Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsushi Kawada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Tominaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Iwata Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Edamura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences For small renal tumors, nephron‑preserving treatment, including partial nephrectomy or ablation therapy, is recommended. According to major guidelines, ablation therapies are advised for patients who are deemed not suitable to undergo surgery due to an advanced age or the presence of comorbidities. However, compared with surgery, ablation therapy can result in superior safety and functional outcomes. The present review discusses the factors affecting decision‑making as regards treatment options for small renal tumors. When determining an appropriate treatment option, tumor locations, as well as the condition and preferences of the patient, are considered. Scoring systems, such as the RENAL Nephrometry Score can assist in guiding treatment decisions. However, surgery may be the preferred approach for tumors near major vessels and collecting systems. For endophytic tumors, partial nephrectomy can be challenging due to the difficulty in visualizing intra‑parenchymal tumors during the procedure, whereas ablation therapies may be inferior to partial nephrectomy. Although treatment selection for small renal tumors can be affected by tumor location, partial nephrectomy remains the gold standard for numerous cases. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 26 15 2025 Acquired Radioresistance Through Adaptive Evolution with Gamma Radiation as Selection Pressure: Increased Expression and Induction of Anti-Stress Genes 7275 EN Takeshi Saito Division of Radiation Life Science, Institute for Integrated Radiation and Nuclear Science, Kyoto University Hiroaki Terato Department of Radiation Research, Advanced Science Research Center, Okayama University Elucidating the mechanisms of radioresistance in highly radiotolerant organisms can provide valuable insights into the adaptation and evolution of organisms. However, research has been limited on many naturally occurring radioresistant organisms due to a lack of information regarding their genetic and biochemical characteristics and the difficulty of handling them experimentally. To address this, we conducted an experiment on adaptive evolution using gamma radiation as the selection pressure to generate evolved Escherichia coli with gamma radiation resistance approximately one order of magnitude greater than that of wild-type E. coli. Gene expressions in all wild-type and evolved radioresistant E. coli in the presence or absence of gamma irradiation were analyzed and compared using RNA sequencing. Under steady-state conditions, the genes involved in survival, cell recovery, DNA repair, and response following stress exposure were upregulated in evolved E. coli compared with those in wild-type E. coli. Furthermore, the evolved E. coli induced these genes more efficiently following gamma irradiation and greater DNA repair activity than that in the wild-type E. coli. Our results indicate that an increased steady-state expression of various anti-stress genes, including DNA repair-related genes, and their highly efficient induction under irradiation are responsible for the remarkable radioresistance of evolved E. coli. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2192-2640 14 10 2024 Biocompatibility of Water-Dispersible Pristine Graphene and Graphene Oxide Using a Close-to-Human Animal Model: A Pilot Study on Swine 2401783 EN Paola Nicolussi Istituto Zooprofilattico Sperimentale della Sardegna Giovannantonio Pilo Istituto Zooprofilattico Sperimentale della Sardegna Maria Giovanna Cancedda Istituto Zooprofilattico Sperimentale della Sardegna Guotao Peng Institute of Environmental Medicine, Karolinska Institutet Ngoc Do Quyen Chau CNRS, Immunology, Immunopathology and Therapeutic Chemistry Alejandro De la Cadena Dipartimento di Fisica, Politecnico di Milano Renzo Vanna Istituto di Fotonica e Nanotecnologie – CNR Yarjan Abdul Samad Cambridge Graphene Centre, University of Cambridge Tanweer Ahmed Cambridge Graphene Centre, University of Cambridge Jeremia Marcellino Cambridge Graphene Centre, University of Cambridge Giuseppe Tedde Istituto Zooprofilattico Sperimentale della Sardegna Linda Giro ImmuneNano Laboratory, Department of Biomedical Sciences Acelya Ylmazer Department of Biomedical Engineering, Ankara University Federica Loi Istituto Zooprofilattico Sperimentale della Sardegna Gavina Carta Istituto Zooprofilattico Sperimentale della Sardegna Loredana Secchi Istituto Zooprofilattico Sperimentale della Sardegna Silvia Dei Giudici Istituto Zooprofilattico Sperimentale della Sardegna Simona Macciocu Istituto Zooprofilattico Sperimentale della Sardegna Dario Polli Dipartimento di Fisica, Politecnico di Milano Yuta Nishina Graduate School of Natural Science and Technology, Okayama University Ciriaco Ligios Istituto Zooprofilattico Sperimentale della Sardegna Giulio Cerullo Dipartimento di Fisica, Politecnico di Milano Andrea Ferrari Cambridge Graphene Centre, University of Cambridge Alberto Bianco CNRS, Immunology, Immunopathology and Therapeutic Chemistry Bengt Fadeel Institute of Environmental Medicine, Karolinska Institutet Giulia Franzoni Istituto Zooprofilattico Sperimentale della Sardegna Lucia Gemma Delogu ImmuneNano Laboratory, Department of Biomedical Sciences 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. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2694-2496 4 4 2024 Light-Responsive and Antibacterial Graphenic Materials as a Holistic Approach to Tissue Engineering 263 272 EN Andrea Ferreras Department of Bioengineering, Universidad Carlos III de Madrid Ana Matesanz Department of Electronic Technology, Universidad Carlos III de Madrid Jabier Mendizabal Domotek ingeniería prototipado y formación S.L. Koldo Artola Domotek ingeniería prototipado y formación S.L. Yuta Nishina Graduate School of Natural Science and Technology, Okayama University Pablo Acedo Department of Electronic Technology, Universidad Carlos III de Madrid José L. Jorcano Department of Bioengineering, Universidad Carlos III de Madrid Amalia Ruiz Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford Giacomo Reina Empa Swiss Federal Laboratories for Materials Science and Technology Cristina Martín Department of Bioengineering, Universidad Carlos III de Madrid While the continuous development of advanced bioprinting technologies is under fervent study, enhancing the regenerative potential of hydrogel-based constructs using external stimuli for wound dressing has yet to be tackled. Fibroblasts play a significant role in wound healing and tissue implants at different stages, including extracellular matrix production, collagen synthesis, and wound and tissue remodeling. This study explores the synergistic interplay between photothermal activity and nanomaterial-mediated cell proliferation. The use of different graphene-based materials (GBM) in the development of photoactive bioinks is investigated. In particular, we report the creation of a skin-inspired dressing for wound healing and regenerative medicine. Three distinct GBM, namely, graphene oxide (GO), reduced graphene oxide (rGO), and graphene platelets (GP), were rigorously characterized, and their photothermal capabilities were elucidated. Our investigations revealed that rGO exhibited the highest photothermal efficiency and antibacterial properties when irradiated, even at a concentration as low as 0.05 mg/mL, without compromising human fibroblast viability. Alginate-based bioinks alongside human fibroblasts were employed for the bioprinting with rGO. The scaffold did not affect the survival of fibroblasts for 3 days after bioprinting, as cell viability was not affected. Remarkably, the inclusion of rGO did not compromise the printability of the hydrogel, ensuring the successful fabrication of complex constructs. Furthermore, the presence of rGO in the final scaffold continued to provide the benefits of photothermal antimicrobial therapy without detrimentally affecting fibroblast growth. This outcome underscores the potential of rGO-enhanced hydrogels in tissue engineering and regenerative medicine applications. Our findings hold promise for developing game-changer strategies in 4D bioprinting to create smart and functional tissue constructs with high fibroblast proliferation and promising therapeutic capabilities in drug delivery and bactericidal skin-inspired dressings. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0008-6223 238 2025 Grafting-through functionalization of graphene oxide with cationic polymers for enhanced adsorption of anionic dyes and viruses 120296 EN Ryota Kimura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Pilar Ferré-Pujol Research Core for Interdisciplinary Sciences, Okayama University Yuta Nishina Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Graphene oxide (GO) is a sheet-like carbon material with abundant oxygen-containing functional groups on its surface. GO has been extensively studied as an adsorbent for heavy metals and organic compounds. However, effective strategies for negatively charged materials have yet to be established. This study aimed to synthesize composites of GO and cationic polymers for the selective adsorption of negatively charged materials; a challenge in this approach is the strong electrostatic interactions between GO and cationic polymers, which can lead to aggregation. This study addresses this issue by employing the grafting-through method. GO was initially modified with allylamine to introduce a polymerizable site, followed by radical polymerization to covalently bond polymers to the GO surface, effectively preventing aggregation. Adsorption experiments demonstrated that the GO-polymer composite selectively adsorbs anionic dye, such as methyl orange. Virus adsorption tests showed significantly enhanced performance compared to pristine GO. These results emphasize the critical role of controlled surface modification and charge manipulation in optimizing the adsorption performance of GO. This study establishes a simple and effective approach for synthesizing GO-cationic polymer composites, contributing to the development of advanced materials for water purification applications. No potential conflict of interest relevant to this article was reported.

Springer Nature Singapore Acta Medica Okayama 0302-9743 2025 RKPM: Restricted Kernel Page Mechanism to Mitigate Privilege Escalation Attacks 213 231 EN Hiroki Kuzuno Graduate School of Engineering, Kobe University Toshihiro Yamauchi Faculty of Environmental, Life, Natural Science and Technology, Okayama University 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. No potential conflict of interest relevant to this article was reported.

IEEE Acta Medica Okayama 2024 kdMonitor: Kernel Data Monitor for Detecting Kernel Memory Corruption 66 73 EN Hiroki Kuzuno Graduate School of Engineering, Kobe University Toshihiro Yamauchi Okayama University,Faculty of Environmental, Life, Natural Science and Technology 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 %. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1999-4923 17 7 2025 Development of an Antimicrobial Coating Film for Denture Lining Materials 902 EN Kumiko Yoshihara National Institute of Advanced Industrial Science and Technology (AIST), Health and Medical Research Institute Takeru Kameyama Graduate School of Natural Science and Technology, Okayama University Noriyuki Nagaoka Dental School, Advanced Research Center for Oral and Craniofacial Science, Okayama University Yukinori Maruo Department of Prosthodontics, Okayama University Yasuhiro Yoshida Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Bart Van Meerbeek BIOMAT, Department of Oral Health Sciences, KU Leuvem Takumi Okihara Graduate School of Natural Science and Technology, Okayama University Background/Objectives: Denture hygiene is essential for the prevention of oral candidiasis, a condition frequently associated with Candida albicans colonization on denture surfaces. Cetylpyridinium chloride (CPC)-loaded montmorillonite (CPC-Mont) has demonstrated antimicrobial efficacy in tissue conditioners and demonstrates potential for use in antimicrobial coatings. In this study, we aimed to develop and characterize CPC-Mont-containing coating films for dentures, focusing on their physicochemical behaviors and antifungal efficacies. Methods: CPC was intercalated into sodium-type montmorillonite to prepare CPC-Mont; thereafter, films containing CPC-Mont were fabricated using emulsions of different polymer types (nonionic, cationic, and anionic). CPC loading, release, and recharging behaviors were assessed at various temperatures, and activation energies were calculated using Arrhenius plots. Antimicrobial efficacy against Candida albicans was evaluated for each film using standard microbial assays. Results: X-ray diffraction analysis confirmed the expansion of montmorillonite interlayer spacing by approximately 3 nm upon CPC loading. CPC-Mont showed temperature-dependent release and recharging behavior, with higher temperatures enhancing its performance. The activation energy for CPC release was 38 kJ/mol, while that for recharging was 26 kJ/mol. Nonionic emulsions supported uniform CPC-Mont dispersion and successful film formation, while cationic and anionic emulsions did not. CPC-Mont-containing coatings maintained antimicrobial activity against Candida albicans on dentures. Conclusions: CPC-Mont can be effectively incorporated into nonionic emulsion-based films to create antimicrobial coatings for denture applications. The films exhibited temperature-responsive, reversible CPC release and recharging behaviors, while maintaining antifungal efficacy, findings which suggest the potential utility of CPC-Mont-containing films as a practical strategy to prevent denture-related candidiasis. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0960-7412 121 5 2025 Spider mite tetranins elicit different defense responses in different host habitats e70046 EN Yukiko Endo Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science Miku Tanaka Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science Takuya Uemura Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science Kaori Tanimura Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science Yoshitake Desaki Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science Rika Ozawa Center for Ecological Research, Kyoto University Sara Bonzano Department of Life Sciences and Systems Biology, Plant Physiology Unit, University of Turin Massimo E. Maffei Department of Life Sciences and Systems Biology, Plant Physiology Unit, University of Turin Tomonori Shinya Institute of Plant Science and Resources (IPSR), Okayama University Ivan Galis Institute of Plant Science and Resources (IPSR), Okayama University Gen‐ichiro Arimura Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science Spider mites (Tetranychus urticae) are a major threat to economically important crops. Here, we investigated the potential of tetranins, in particular Tet3 and Tet4, as T. urticae protein-type elicitors that stimulate plant defense. Truncated Tet3 and Tet4 proteins showed efficacy in activating the defense gene pathogenesis-related 1 (PR1) and inducing phytohormone production in leaves of Phaseolus vulgaris. In particular, Tet3 caused a drastically higher Ca2+ influx in leaves, but a lower reactive oxygen species (ROS) generation compared to other tetranins, whereas Tet4 caused a low Ca2+ influx and a high ROS generation in the host plants. Such specific and non-specific elicitor activities were examined by knockdown of Tet3 and Tet4 expressions in mites, confirming their respective activities and in particular showing that they function additively or synergistically to induce defense responses. Of great interest is the fact that Tet3 and Tet4 expression levels were higher in mites on their preferred host, P. vulgaris, compared to the levels in mites on the less-preferred host, Cucumis sativus, whereas Tet1 and Tet2 were constitutively expressed regardless of their host. Furthermore, mites that had been hosted on C. sativus induced lower levels of PR1 expression, Ca2+ influx and ROS generation, i.e., Tet3- and Tet4-responsive defense responses, in both P. vulgaris and C. sativus leaves compared to the levels induced by mites that had been hosted on P. vulgaris. Taken together, these findings show that selected tetranins respond to variable host cues that may optimize herbivore fitness by altering the anti-mite response of the host plant. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1477-0520 2025 From Carboxylic Acids or Their Derivatives to Amines and Ethers: Modern Decarboxylative Approaches for Sustainable C–N and C–O Bond Formation EN Weidan Yan Graduate School of Natural Science and Technology, Okayama University Tian Tian Graduate School of Natural Science and Technology, Okayama University Yasushi Nishihara Research Institute for Interdisciplinary Science (RIIS), Okayama University Amines and ethers represent essential structural motifs in pharmaceuticals, natural products, organic materials, and catalytic systems. The development of novel, environmentally friendly, and cost-effective strategies for constructing C–N and C–O bonds is therefore of significant importance for the synthesis of these compounds. In recent years, carboxylic acids and their derivatives have emerged as attractive, inexpensive, non-toxic, and readily available synthetic building blocks, serving as promising alternatives to aryl halides. Growing evidence has demonstrated that decarboxylative amination and etherification of carboxylic acid derivatives offer a powerful approach for the synthesis of amines and ethers. These transformations proceed via three principal mechanistic pathways, each offering high atom economy. Specifically, carbanions (or organometallic species) generated through heterolytic decarboxylation can react with suitable electrophiles to form C–heteroatom bonds. In contrast, carbon-centred radicals produced through homolytic decarboxylation can couple with heteroatom-based reagents via radical recombination or oxidative trapping. Additionally, carbocations are typically formed via electrochemical oxidation of carboxylic acids: oxidative decarboxylation first yields a carbon radical, which is then further oxidized at the anode to generate a carbocation. This highly electrophilic intermediate can subsequently be intercepted by heteroatom nucleophiles to construct C–N or C–O bonds. This review highlights recent advances in the field, with a focus on transition metal catalysis, photoredox catalysis, and electrochemical methods for decarboxylative amination and etherification. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0040-4039 169 2025 Recent progress on phenothiazine organophotoredox catalysis 155745 EN Kenta Tanaka Research Institute for Interdisciplinary Science, Okayama University Hiroyoshi Takamura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Isao Kadota Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Photoredox catalysis has garnered significant attention in recent years due to its broad applicability in visible-light-induced organic transformations. While significant progress has been made in the development of highly oxidizing catalysts, such as acridinium catalysts, there remains a notable shortage of strongly reducing organophotoredox catalysts. Phenothiazines are widely used as photoredox catalysts owing to their unique redox potentials, particularly their low excited-state oxidation potentials (Eox* = −1.35 V to −3.51 V vs. SCE). Thus, they can be applied to a variety of photoredox reactions with oxidative-quenching cycles, and effectively reduce various organic molecules, such as aryl and alkyl halides, alkenes, malonyl peroxides, cobalt complexes, and redox-active esters. Due to their unique properties, this review focuses on the recent advances in phenothiazine organophotoredox catalysis. No potential conflict of interest relevant to this article was reported.

American Astronomical Society Acta Medica Okayama 0004-637X 965 1 2024 Unraveling the Cr Isotopes of Ryugu: An Accurate Aqueous Alteration Age and the Least Thermally Processed Solar System Material 52 EN Ryoji Tanaka The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Dilan M. Ratnayake The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Tsutomu Ota The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Noah Miklusicak The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Tak Kunihiro The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Christian Potiszil The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Chie Sakaguchi The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Katsura Kobayashi The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Hiroshi Kitagawa The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Masahiro Yamanaka The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Masanao Abe Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Akiko Miyazaki Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Aiko Nakato Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Satoru Nakazawa Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Masahiro Nishimura Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Tatsuaki Okada Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Takanao Saiki Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Satoshi Tanaka Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Fuyuto Terui Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Yuichi Tsuda Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Tomohiro Usui Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Sei-ichiro Watanabe Department of Earth and Planetary Sciences, Nagoya University Toru Yada Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Kasumi Yogata Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Makoto Yoshikawa Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Eizo Nakamura The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University The analysis of samples returned from the C-type asteroid Ryugu has drastically advanced our knowledge of the evolution of early solar system materials. However, no consensus has been obtained on the chronological data, which is important for understanding the evolution of the asteroid Ryugu. Here, the aqueous alteration age of Ryugu particles was determined by the Mn–Cr method using bulk samples, yielding an age of 4.13 + 0.62/−0.55 Myr after the formation of Ca–Al-rich inclusions (CAI). The age corresponds to 4563.17 + 0.60/−0.67 Myr ago. The higher 55Mn/52Cr, ε54Cr, and initial ε53Cr values of the Ryugu samples relative to any carbonaceous chondrite samples implies that its progenitor body formed from the least thermally processed precursors in the outermost region of the protoplanetary disk. Despite accreting at different distances from the Sun, the hydrous asteroids (Ryugu and the parent bodies of CI, CM, CR, and ungrouped C2 meteorites) underwent aqueous alteration during a period of limited duration (3.8 ± 1.8 Myr after CAI). These ages are identical to the crystallization age of the carbonaceous achondirtes NWA 6704/6693 within the error. The ε54Cr and initial ε53Cr values of Ryugu and NWA 6704/6693 are also identical, while they show distinct Δ'17O values. This suggests that the precursors that formed the progenitor bodies of Ryugu and NWA 6703/6693 were formed in close proximity and experienced a similar degree of thermal processing in the protosolar nebula. However, the progenitor body of Ryugu was formed by a higher ice/dust ratio, than NWA6703/6693, in the outer region of the protoplanetary disk. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1068-9265 2025 Tumor Microvessels with Specific Morphology as a Prognostic Factor in Esophageal Squamous Cell Carcinoma EN Hnin Thida Tun Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Seitaro Nishimura Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoyoshi Kunitomo Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Noma Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Angiogenesis is essential for tumor progression. Microvessel density (MVD) is a widely used histological method to assess angiogenesis using immunostained sections, but its prognostic significance in esophageal cancer remains controversial. Recently, the evaluation of microvascular architecture has gained importance as a method to assess tumor aggressiveness. The present study aimed to identify the histological characteristics of tumor microvessels that are associated with the aggressiveness of esophageal squamous cell carcinoma.<br> Patients and Methods A total of 108 esophageal squamous cell carcinoma tissues were immunohistochemically stained with blood vessel markers and angiogenesis-related markers, including CD31, alpha smooth muscle actin, vascular endothelial growth factor A (VEGF-A), CD206, and D2-40. MVD, microvessel pericyte coverage index (MPI), and tumor vascular morphology were evaluated by microscopy.<br> Results MVD was significantly associated with patient outcomes, whereas neither MPI nor VEGF-A expression throughout the tumor showed a significant correlation. In addition, the presence of blood vessels encircling clusters of tumor cells, termed C-shaped microvessels, and excessively branching microvessels, termed X-shaped microvessels, was significantly associated with poor prognosis. These vessel types were also correlated with clinicopathological parameters, including deeper invasion of the primary tumor, presence of lymph node metastasis, advanced pathological stage, and distant metastasis. Focal VEGF-A immunoexpression in tumor cells was higher in areas containing C-shaped or X-shaped microvessels compared with areas lacking these vessel morphologies.<br> Conclusions The data suggest that tumor microvessels with specific morphologies (C-shaped and X-shaped microvessels) may serve as a promising prognostic factor in esophageal squamous cell carcinoma. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2041-1723 15 1 2024 A high-protein diet-responsive gut hormone regulates behavioral and metabolic optimization in Drosophila melanogaster 10819 EN Yuto Yoshinari Metabolic Regulation and Genetics, Institute for Molecular and Cellular Regulation, Gunma University Takashi Nishimura Metabolic Regulation and Genetics, Institute for Molecular and Cellular Regulation, Gunma University Taishi Yoshii Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Shu Kondo Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science Hiromu Tanimoto Graduate School of Life Sciences, Tohoku University Tomoe Kobayashi Division of Molecular Genetics, Shigei Medical Research Institute Makoto Matsuyama Division of Molecular Genetics, Shigei Medical Research Institute Ryusuke Niwa Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba Protein is essential for all living organisms; however, excessive protein intake can have adverse effects, such as hyperammonemia. Although mechanisms responding to protein deficiency are well-studied, there is a significant gap in our understanding of how organisms adaptively suppress excessive protein intake. In the present study, utilizing the fruit fly, Drosophila melanogaster, we discover that the peptide hormone CCHamide1 (CCHa1), secreted by enteroendocrine cells in response to a high-protein diet (HPD), is vital for suppressing overconsumption of protein. Gut-derived CCHa1 is received by a small subset of enteric neurons that produce short neuropeptide F, thereby modulating protein-specific satiety. Importantly, impairment of the CCHa1-mediated gut-enteric neuronal axis results in ammonia accumulation and a shortened lifespan under HPD conditions. Collectively, our findings unravel the crosstalk of gut hormone and neuronal pathways that orchestrate physiological responses to prevent and adapt to dietary protein overload. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2198-3844 12 18 2025 Cryo-EM Analysis of a Tri-Heme Cytochrome-Associated RC-LH1 Complex from the Marine Photoheterotrophic Bacterium Dinoroseobacter Shibae 2413456 EN Weiwei Wang College of Life Sciences, Zhejiang University Yanting Liu State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University Jiayi Gu College of Life Sciences, Zhejiang University Shaoya An Department of Pathology of Sir Run Run Shaw Hospital, Department of Biophysics, Zhejiang University School of Medicine Cheng Ma Department of Pathology of Sir Run Run Shaw Hospital, Department of Biophysics, Zhejiang University School of Medicine Haichun Gao College of Life Sciences, Zhejiang University Nianzhi Jiao State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University Jian‐Ren Shen Research Institute for Interdisciplinary Science, and Graduate School of Natural Science and Technology, Okayama University John Thomas Beatty Department of Microbiology & Immunology, University of British Columbia Michal Koblížek Laboratory of Anoxygenic Phototrophs, Institute of Microbiology, Czech Academy of Science Xing Zhang Department of Pathology of Sir Run Run Shaw Hospital, Department of Biophysics, Zhejiang University School of Medicine Qiang Zheng State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University Jing‐Hua Chen College of Life Sciences, Zhejiang University The reaction center-light harvesting 1 (RC-LH1) complex converts solar energy into electrical energy, driving the initiation of photosynthesis. The authors present a cryo-electron microscopy structure of the RC-LH1 isolated from a marine photoheterotrophic bacterium Dinoroseobacter shibae. The RC comprises four subunits, including a three-heme cytochrome (Cyt) c protein, and is surrounded by a closed LH ring composed of 17 pairs of antenna subunits. Notably, a novel subunit with an N-terminal “helix-turn-helix” motif embedded in the gap between the RC and the LH ring is identified. The purified RC-LH1 complex exhibits high stability in solutions containing Mg2+ or Ca2+. The periplasmic Cyt c2 is predicted to bind at the junction between the Cyt subunit and the membrane plane, enabling electron transfer from Cyt c2 to the proximal heme of the tri-heme Cyt, and subsequently to the special pair of bacteriochlorophylls. These findings provide structural insights into the efficient energy and electron transfer processes within a distinct type of RC-LH1, and shed light on evolutionary adaptations of photosynthesis. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0910-6340 2025 Innovations in paper-based analytical devices and portable absorption photometers for onsite analysis EN Sasikarn Seetasang Department of Chemistry, Faculty of Science and Technology, Thammasat University Mika I. Umeda Department of Chemistry, Okayama University Jianchao Ren Department of Chemistry, Okayama University Takashi Kaneta Department of Chemistry, Okayama University Two types of analytical instruments and devices—one sophisticated high-performance instrument and another portable device—have been the focus of recent trends in analytical science. The necessity of point-of-care testing and onsite analysis has accelerated the advancement of high-performance, user-friendly portable analytical devices such as paper-based analytical devices (PADs) and light-emitting diode-based portable photometers. In this review, we summarize our achievements in the study of PADs and portable photometers. Several types of PADs are capable of performing titrations, metal ion analysis, and food analysis, while photometers, which consist of paired emitter–detector light-emitting diode (PEDD) photometers, are used for thiocyanate and herbicide analysis. These PADs and photometers permit the onsite determination of real environmental, body fluid, and food samples when an equipped laboratory is unavailable. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0960-9822 35 12 2025 Oxytocin facilitates human touch-induced play behavior in rats 2916 2926.e3 EN Himeka Hayashi Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University, Sayaka Tateishi Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University Ayumu Inutsuka Division of Brain and Neurophysiology, Department of Physiology, Jichi Medical University Sho Maejima Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University Daisuke Hagiwara Department of Neuropeptide Research in Psychiatry, Central Institute of Mental Health, German Center for Psychiatry (DZPG), Medical Faculty Mannheim, University of Heidelberg Yasuo Sakuma Department of Anatomy and Neurobiology, Graduate School of Medical Sciences, Nippon Medical School Tatsushi Onaka Division of Brain and Neurophysiology, Department of Physiology, Jichi Medical University Valery Grinevich Department of Neuropeptide Research in Psychiatry, Central Institute of Mental Health, German Center for Psychiatry (DZPG), Medical Faculty Mannheim, University of Heidelberg Hirotaka Sakamoto Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University, Pleasant touch sensations play a fundamental role in social bonding, yet the neural mechanisms underlying affinity-like behaviors remain poorly understood. Here, we demonstrate that juvenile-adolescent rats, which naturally engage in social play with peers characterized by rough-and-tumble interactions and 50 kHz ultrasonic vocalizations indicating pleasant sensations, develop a strong affinity for human hands through similar playful contact achieved by repeated tickling with human hands. Using this rat with tickling-induced high affinity for human hands, we discovered that repeated tickling mimicking rough-and-tumble play led to increased oxytocin receptor (OTR) expression in the ventrolateral part of the ventromedial hypothalamus (VMHvl). Inhibition of oxytocin signaling in the VMHvl reduced affinity-like behaviors from rats to human hands. These findings suggest that OTR neurons in VMHvl play an important role in the increase in affinity for human hands induced by pleasant touch sensation with human touch-induced play behavior. Based on retrograde and anterograde tracing studies examining the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) as primary sources of oxytocin, we demonstrate that a subset of oxytocin fibers in the VMHvl originate from the SON, suggesting that affinity-like behavior from rats to human hands may be controlled by oxytocin signaling from magnocellular neurons. Together, this work advances our understanding of how oxytocin shapes social behavior and may inform the development of therapeutic strategies to promote positive social interactions. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1477-0520 2025 One-pot synthesis of trans-2,3-diaminoindolines through 2,3-diamination of electrophilic indolines EN Yuito Kobori Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Despite recent advances in the synthesis of 2,3-diaminoindole derivatives, construction of 2,3-diaminoindolines, whose two amine moieties on each molecule differ from one another has yet to be achieved. In this work, we developed a concise one-pot protocol for differentiated diamination involving reacting a C2,C3-electrophilic indole reagent with amines to access a variety of previously inaccessible 2,3-diaminoindolines. Furthermore, the synthetic utility of this protocol was demonstrated by a successful gram-scale reaction and further transformation of the 2,3-diaminoindolines. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 1109-6535 22 4 2025 C1orf50 Drives Malignant Melanoma Progression Through the Regulation of Stemness 510 524 EN YUSUKE OTANI Department of Pathology, Beth Israel Deaconess Medical Center MASAKI MAEKAWA Department of Pathology, Beth Israel Deaconess Medical Center ATSUSHI TANAKA Department of Pathology, Beth Israel Deaconess Medical Center TIRSO PEÑA Department of Pathology, Beth Israel Deaconess Medical Center VANESSA D. CHIN UMass Chan Medical School, UMass Memorial Medical Center ANNA ROGACHEVSKAYA Department of Pathology, Beth Israel Deaconess Medical Center SHINICHI TOYOOKA Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences MICHAEL H. ROEHRL Department of Pathology, Beth Israel Deaconess Medical Center ATSUSHI FUJIMURA Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Aim: Recent advancements in omics analysis have significantly enhanced our understanding of the molecular pathology of malignant melanoma, leading to the development of novel therapeutic strategies that target specific vulnerabilities within the disease. Despite these improvements, the factors contributing to the poor prognosis of patients with malignant melanoma remain incompletely understood. The aim of this study was to investigate the role of C1orf50 (Chromosome 1 open reading frame 50), a gene previously of unknown function, as a prognostic biomarker in melanoma.<br> Materials and Methods: We performed comprehensive transcriptome data analysis and subsequent functional validation of the human Skin Cutaneous Melanoma project from The Cancer Genome Atlas (TCGA).<br> Results: Elevated expression levels of C1orf50 correlated with worse survival outcomes. Mechanistically, we revealed that C1orf50 plays a significant role in the regulation of cell cycle processes and cancer cell stemness, providing a potential avenue for novel therapeutic interventions in melanoma.<br> Conclusion: This study is the first to identify C1orf50 as a prognostic biomarker in melanoma. The clinical relevance of our results sheds light on the importance of further investigation into the biological mechanisms underpinning C1orf50’s impact on melanoma progression and patient prognosis. No potential conflict of interest relevant to this article was reported.

Springer International Publishing Acta Medica Okayama 0302-9743 2022 CyNER: Information Extraction from Unstructured Text of CTI Sources with Noncontextual IOCs 85 104 EN Shota Fujii Graduate School of Natural Science and Technology, Okayama University Nobutaka Kawaguchi Research & Development Group, Hitachi, Ltd. Tomohiro Shigemoto Research & Development Group, Hitachi, Ltd. Toshihiro Yamauchi Faculty of Natural Science and Technology, Okayama University Cybersecurity threats have been increasing and growing more sophisticated year by year. In such circumstances, gathering Cyber Threat Intelligence (CTI) and following up with up-to-date threat information is crucial. Structured CTI such as Structured Threat Information eXpression (STIX) is particularly useful because it can automate security operations such as updating FW/IDS rules and analyzing attack trends. However, as most CTIs are written in natural language, manual analysis with domain knowledge is required, which becomes quite time-consuming.<br> In this work, we propose CyNER, a method for automatically structuring CTIs and converting them into STIX format. CyNER extracts named entities in the context of CTI and then extracts the relations between named entities and IOCs in order to convert them into STIX. In addition, by using key phrase extraction, CyNER can extract relations between IOCs that lack contextual information, such as those listed at the bottom of a CTI, and named entities. We describe our design and implementation of CyNER and demonstrate that it can extract named entities with the F-measure of 0.80 and extract relations between named entities and IOCs with the maximum accuracy of 81.6%. Our analysis of structured CTI showed that CyNER can extract IOCs that are not included in existing reputation sites, and that it can automatically extract IOCs that have been exploited for a long time and across multiple attack groups. CyNER is thus expected to contribute to the efficiency of CTI analysis. No potential conflict of interest relevant to this article was reported.

Springer Nature Switzerland Acta Medica Okayama 2367-4512 2025 Investigation Towards Detecting Landing Websites for Fake Japanese Shopping Websites 107 119 EN Daigo Michishita Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Satoru Kobayashi Faculty of Environmental, Life, Natural Science and Technology, Okayama University Toshihiro Yamauchi Faculty of Environmental, Life, Natural Science and Technology, Okayama University Recently, the number of victims of fake shopping websites that imitate legitimate ones to defraud people has been increasing. It has been shown that fake shopping websites use legitimate defaced landing websites as their leading paths. Therefore, if the detection of landing websites for fake shopping websites can be achieved, it can assist in addressing these websites and reduce the opportunities for users to be redirected to fake shopping websites. In this study, we collect and investigate existing landing websites that redirect users to fake Japanese shopping websites and identify effective features for detecting them. We identified effective search terms for collecting landing websites for fake Japanese shopping websites and found that using Google searches with queries of top-level domain and product names was effective. We also investigated the conditions for activating analytical evasion functions in the collected landing websites for fake Japanese shopping websites and clarified the differences in search results between crawlers and users. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1865-0333 18 1 2024 Standardization of radiation therapy quality control system through mutual quality control based on failure mode and effects analysis 78 85 EN Yuki Tanimoto Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masataka Oita Faculty of Interdisciplinary Science and Engineering in Health Systems, Department of Healthcare Science, Okayama University Kazunobu Koshi Department of Radiology, NHO Fukuyama Medical Center Kiyoshi Ishiwaki Department of Radiology, NHO Iwakuni Medical Center Futoshi Hiramatsu Department of Radiology, NHO Hamada Medical Center Toshihisa Sasaki Department of Radiology, NHO Higashi-Hiroshima Medical Center Hiroki Ise Department of Radiology, NHO Iwakuni Medical Center Takashi Miyagawa Department of Radiology, NHO Kanmon Medical Center Takeshi Maeda Department of Radiology, NHO Kochi National Hospital Shinsuke Okahira Department of Radiology, NHO Yamaguchi-Ube Medical Center Takashi Hamaguchi Department of Radiology, NHO Okayama Medical Center Tatsuya Kawaguchi Department of Radiology, NHO Shikoku Medical Center for Children and Adults Norihiro Funada Department of Radiology, NHO Hamada Medical Center Shuhei Yamamoto Department of Radiology, NHO Fukuyama Medical Center Akira Hiroshige Department of Radiology, NHO Shikoku Cancer Center Yuki Mukai Department of Radiology, NHO Shikoku Cancer Center Shohei Yoshida Department of Radiology, NHO Shikoku Cancer Center Yoshiki Fujita Department of Radiology, NHO Shikoku Cancer Center Atsuki Nakahira Department of Radiology, NHO Shikoku Cancer Center Hirofumi Honda Department of Radiological Technology, Ehime University Hospital The advancement of irradiation technology has increased the demand for quality control of radiation therapy equipment. Consequently, the number of quality control items and required personnel have also increased. However, differences in the proportion of qualified personnel to irradiation techniques have caused bias in quality control systems among institutions. To standardize the quality across institutions, researchers should conduct mutual quality control by analyzing the quality control data of one institution at another institution and comparing the results with those of their own institutions. This study uses failure mode and effects analysis (FMEA) to identify potential risks in 12 radiation therapy institutions, compares the results before and after implementation of mutual quality control, and examines the utility of mutual quality control in risk reduction. Furthermore, a cost-effectiveness factor is introduced into FMEA to evaluate the utility of mutual quality control. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Ramucirumab in second‑line advanced colorectal cancer therapy: A study on therapeutic outcomes and hepatic sinusoidal platelet aggregation EN Keisuke KIMURA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Low frequency of intracranial progression in advanced NSCLC patients treated with cancer immunotherapies EN Naoya KEMMOTSU Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2632-2498 7 1 2025 Evaluating short-term survivors of glioblastoma: A proposal based on SEER registry data vdaf036 EN Yusuke Tomita Department of Neurological Surgery, Okayama University Medical School Yoshihiro Otani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Omae Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Mizuta Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Joji Ishida Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuyuki Hirotsune Department of Neurosurgery and Neuroendovascular Surgery, Hiroshima City Hiroshima Citizens Hospital Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Glioblastomas (GBMs) are central nervous system tumors with a poor prognosis and limited treatment options. Although small subsets of GBM patients survive longer than 3 years, there is little evidence regarding the prognostic factors of GBM. Therefore, we conducted a thorough characterization of GBM in the United States.<br> Methods: We queried the Surveillance, Epidemiology, and End Results database between 2000 and 2021 to extract age-adjusted incidence rates (AAIRs), age-adjusted mortality rates (AAMRs), and survival data for GBM. We compared trends in AAIR, AAMR, and survival time across age groups 0–14, 15–39, 40–69, and 70+ years. Also, we employed the Fine–Gray competing risk model among short-term survivors (STSs), defined as those with a survival time of 6 months or less, and long-term survivors (LTSs), defined as those with a survival time of 3 years or more.<br> Results: This study included 60 615 incident GBM cases, 54 998 GBM-specific deaths, and 47 207 GBM patients with available survival time between 2000 and 2021. The mortality-to-incidence ratio was constant among STSs, whereas it increased with age among LTSs. Higher age and male sex were significantly associated with GBM-specific death among LTSs, whereas non-Hispanic White and less intensive treatments were associated with GBM-specific deaths among STSs. Interestingly, higher age was significantly associated with other causes of death among STSs.<br> Conclusions: STSs partially consist of populations who died from causes other than GBM. It is important to include only GBM-specific deaths in STS groups to conduct reproducible research comparing STSs and LTSs. No potential conflict of interest relevant to this article was reported.

American Association for the Advancement of Science Acta Medica Okayama 2375-2548 11 20 2025 Structure of a photosystem I supercomplex from Galdieria sulphuraria close to an ancestral red alga eadv7488 EN Koji Kato Research institute for interdisciplinary Science and Graduate School of environ-mental, life, natural Science and technology, Okayama University Minoru Kumazawa Graduate School of Agriculture, Kyoto University Yoshiki Nakajima Research institute for interdisciplinary Science and Graduate School of environ-mental, life, natural Science and technology, Okayama University Takehiro Suzuki Biomolecular characterization Unit, RiKen center for Sustainable Resource Science Naoshi Dohmae Biomolecular characterization Unit, RiKen center for Sustainable Resource Science Jian-Ren Shen Research institute for interdisciplinary Science and Graduate School of environ-mental, life, natural Science and technology, Okayama University Kentaro Ifuku Graduate School of Agriculture, Kyoto University Ryo Nagao Faculty of Agriculture, Shizuoka University Red algae exhibit unique photosynthetic adaptations, characterized by photosystem I (PSI) supercomplexes containing light-harvesting complexes (LHCs), forming PSI-LHCI supercomplexes. In this study, we solved the PSI-LHCI structure of Galdieria sulphuraria NIES-3638 at 2.19-angstrom resolution using cryo-electron microscopy, revealing a PSI monomer core associated with seven LHCI subunits. Structural analysis uncovered the absence of phylloquinones, the common secondary electron acceptor in PSI of photosynthetic organisms, suggesting adaptation to a benzoquinone-like molecule. Phylogenetic analysis suggests that G. sulphuraria retains traits characteristic of an ancestral red alga, including distinctive LHCI binding and interaction patterns. Variations in LHCI composition and interactions across red algae, particularly in red-lineage chlorophyll a/b-binding-like protein and red algal LHCs, highlight evolutionary divergence and specialization. These findings not only deepen our understanding of red algal PSI-LHCI diversification but also enable us to predict features of an ancestral red algal PSI-LHCI supercomplex, providing a framework to explore evolutionary adaptations from an ancestral red alga. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2041-1723 16 1 2025 Structure of a photosystem II-FCPII supercomplex from a haptophyte reveals a distinct antenna organization 4175 EN Romain La Rocca Research Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koji Kato Research Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Pi-Cheng Tsai Research Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiki Nakajima Research Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Fusamichi Akita Research Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Jian-Ren Shen Research Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haptophytes are unicellular algae that produce 30 to 50% of biomass in oceans. Among haptophytes, a subset named coccolithophores is characterized by calcified scales. Despite the importance of coccolithophores in global carbon fixation and CaCO3 production, their energy conversion system is still poorly known. Here we report a cryo-electron microscopic structure of photosystem II (PSII)-fucoxanthin chlorophyll c-binding protein (FCPII) supercomplex from Chyrostila roscoffensis, a representative of coccolithophores. This complex has two sets of six dimeric and monomeric FCPIIs, with distinct orientations. Interfaces of both FCPII/FCPII and FCPII/core differ from previously reported. We also determine the sequence of Psb36, a subunit previously found in diatoms and red algae. The principal excitation energy transfer (EET) pathways involve mainly 5 FCPIIs, where one FCPII monomer mediates EET to CP47. Our findings provide a solid structural basis for EET and energy dissipation pathways occurring in coccolithophores. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 3 2025 A Case of Chromophobe Renal Cell Carcinoma Metastasizing to the Cervical Lymph Nodes after Long-term Follow-up 213 219 EN Makoto Watanabe Department of Otolaryngology, Chugoku Rosai Hospital Tomoyuki Ogawa Department of Otolaryngology, Chugoku Rosai Hospital Kanao Kobayashi Department of Nephrology and Urological Surgery, Chugoku Rosai Hospital Narutaka Katsuya Department of Molecular Pathology, Graduate School of Medical Sciences, Hiroshima University Akira Ishikawa Department of Molecular Pathology, Graduate School of Medical Sciences, Hiroshima University Takao Hamamoto Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital Hiroaki Tahara Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital Tsutomu Ueda Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital Sachio Takeno Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital Case Report 10.18926/AMO/68730 Renal cell carcinoma (RCC) can metastasize hematogenously and recur after a long dormancy. Chromophobe RCC metastasized to the cervical lymph nodes 10 years after the primary resection in a woman who underwent nephrectomy for RCC (T1aN0M0 stage I). Metastatic RCC diagnosis was confirmed by aspiration. The lymph node mass was resected, and the tumor cells matched chromophobe RCC metastasis. No adjuvant therapy was administered due to the lack of evidence regarding adjuvant therapy for chromophobe RCC. Long-term surveillance is crucial in RCC because of the possibility of late metastasis. We reviewed the clinical aspects and literature on metastatic cervical RCC. No potential conflict of interest relevant to this article was reported.