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.

Wiley Acta Medica Okayama 0309-0167 2026 Clinicopathological and transcriptomic profiles of 101 patients with diffuse large B-cell lymphoma/high-grade B-cell lymphoma with double-hit MYC and BCL2 or BCL6 and triple hit EN Masashi Miyaoka Department of Pathology, School of Medicine, Tokai University Joaquim Carreras Department of Pathology, School of Medicine, Tokai University Yara Yukie Kikuti Department of Pathology, School of Medicine, Tokai University Haruka Ikoma Department of Pathology, School of Medicine, Tokai University Shunsuke Nagase Department of Pathology, School of Medicine, Tokai University Atsushi Ito Department of Pathology, School of Medicine Tokai University Isehara Japan Makoto Orita Department of Pathology, School of Medicine, Tokai University Hiroshi Kawada Department of Hematology, School of Medicine, Tokai University Rika Sakai Department of Medical Oncology, Kanagawa Cancer Center Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Kunihiro Tsukasaki Department of Hematology, International Medical Center, Saitama Medical University Shuji Momose Department of Pathology, Saitama Medical Center, Saitama Medical University Yoshihiro Kameoka Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine Masahiro Yoshida Department of Hematology, Osaka City General Hospital Akira Satou Department of Surgical Pathology, Aichi Medical University Hospital Seiichi Kato Center for Clinical Pathology, Fujita Health University Hospital Naoki Oishi Department of Pathology, University of Yamanashi Akio Saito Department of Hematology, NHO Shibukawa Medical Center Ken Sadahira Division of Hematology, Kawasaki Municipal Kawasaki Hospital Yohei Masugi Department of Pathology, School of Medicine, Tokai University Naoya Nakamura Department of Pathology, School of Medicine, Tokai University Aims: Diffuse large B-cell lymphoma/high-grade B-cell lymphoma (DLBCL/HGBCL) with MYC and BCL2 rearrangements (double-hit lymphoma with BCL2, DHL-BCL2) is a mature aggressive B-cell lymphoma that also includes concurrent triple hit with BCL6 translocation (TH). DHL with MYC and BCL6 (DH-BCL6) can also occur. The differences among these three DLBCL/HGBCL subtypes have not yet been definitively determined. Methods and Results: This study characterized the clinicopathological features and transcriptomic profiles of a series of 101 cases of DLBCL/HGBCL that were subclassified according to MYC, BCL2 and BCL6 FISH data, including cell-of-origin (COO)-like, molecular high-grade (MHG)-like and double-hit/dark-zone (DHIT/DZsig)-like signatures. DLBCL/HGBCL-DH-BCL2 was characterized by higher HGBCL morphology, CD10 positivity, GCB Hans's, GCB COO and MHG molecular subtype. DLBCL/HGBCL-TH had higher LDH levels and worse overall survival. DLBCL/HGBCL-DH-BCL6 had higher MUM1 expression, non-GCB Hans', ABC/Unclassified COO, non-MHG and low DHIT/DZ signatures. Transcriptomic analysis showed that DLBCL/HGBCL-DH-BCL2 and DLBCL/HGBCL-TH were close but separated from DLBCL/HGBCL-DH-BCL6. Gene set enrichment analysis (GSEA) revealed different levels of enrichment between the subtypes. Conclusions: DLBCL/HGBCL-DH-BCL6 differs from the DLBCL/HGBCL-DH-BCL2, and the DLBCL/HGBCL-TH is associated with the worst survival. Analysis of all three genes of MYC, BCL2 and BCL6 is recommended in the context of DLBCL/HGBCL diagnosis. 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.

John Wiley & Sons Ltd. Acta Medica Okayama 2314-6133 2025 2025 Comparing the Activity of Peripheral Blood Mononuclear Cells Frozen Under Electromagnetic Field Freezing and Standard Slow-Freezing 9884345 EN Takehiro Matsubara Okayama University Hospital Biobank Mina Takagi Faculty of Health Sciences, Okayama University Medical School Takahiro Uwabo Department of Biorepository Research and Networking, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junichi Soh Department of Thoracic Surgery, Osaka Metropolitan University Graduate School of Medicine Shinichi Toyooka Okayama University Hospital Biobank Mizuki Morita Okayama University Hospital Biobank Peripheral blood mononuclear cells (PBMCs) are cells obtained from the blood that are used not only in clinical tests but also in various research applications. The slow-freezing (SLF) method, currently the standard for PBMC cryopreservation, involves extended storage at −80°C before transfer to liquid nitrogen. Delays in this transfer, such as overnight or weekend holds, risk a gradual decline in cell viability. Additionally, variability in freezing duration can lead to inconsistent cell quality, emphasizing the need for an alternative freezing method that allows for more timely transfer to liquid nitrogen. This study is aimed at clarifying whether the method of using a freezer with an applied electromagnetic field (EMF) is superior to the currently used standard SLF method for PBMC cryopreservation. A comparison of the number of viable cells, cell viability, and cell activity showed that the EMF method was equivalent to the SLF method. However, the shortest time required for freezing was significantly shorter with the EMF method than the SLF method (0.25 vs. 3 h), allowing for earlier transfer of PBMC to liquid nitrogen. This demonstrates that the EMF method offers an advantage in operational efficiency, particularly for facilities that routinely process and store PBMCs, such as biobanks and other storage-focused departments. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0012-1592 68 3 2026 A Simple Method for RNA-Seq of Manually Isolated Chromatophores in Oryzias Fishes e70044 EN Makoto Goda Institute of Photonics Medicine, Hamamatsu University School of Medicine Asuka Miyagi Institute of Photonics Medicine, Hamamatsu University School of Medicine Keisuke Sugiwaka Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University Masakatsu Watanabe Cellular and Structural Physiology Institute (CeSPI) and Graduate School of Pharmaceutical Sciences, Nagoya University Manabu Bessho‐Uehara Frontier Research Institute for Interdisciplinary Science, Tohoku University Masahiko Hibi Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University Atsushi Toyoda Comparative Genomics Laboratory, National Institute of Genetics Rieko Tanaka World Medaka Aquarium, Nagoya Higashiyama Zoo and Botanical Gardens Kawilarang W. A. Masengi Faculty of Fisheries and Marine Science, Sam Ratulangi University Kazunori Yamahira Tropical Biosphere Research Center, University of the Ryukyus Satoshi Ansai Ushimado Marine Institute, Okayama University Hisashi Hashimoto Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University RNA sequencing (RNA-seq) has become an essential tool for analyzing gene expression and exploring cell type–specific transcriptomes. However, sample preparation and quality control remain challenging, as current approaches typically rely on dissecting tissues containing mixed cell populations or using flow cytometry to isolate fluorescently labeled cells. Here we present a simple and reliable method for RNA-seq of chromatophores (pigment cells) by manually isolating cells based on their natural pigmentation. We analyzed four chromatophore types—melanophores, xanthophores, iridophores, and leucophores—in medaka (Oryzias latipes). Remarkably, as few as 100 cells per type yielded reasonably high-quality transcriptomes sufficient to identify differentially expressed genes (DEGs). Furthermore, this method was successfully applied to a non-model medaka species, O. woworae, which shares the same four chromatophore types. Our approach enables efficient, low-cost, and cross-species transcriptome analysis of chromatophores without requiring transgenic markers or flow cytometry. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2398-8835 9 3 2026 Effects of Overload on Imiquimod‐Induced Psoriasis Model Mice: A Basic Experimental Study e72040 EN Tomoki Furutani Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Taichi Saito Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Asahi Ikeda Okayama University Medical School Faculty of Medicine Kenta Mashima Okayama University Medical School Faculty of Medicine Natsumi Yukihiro Okayama University Medical School Faculty of Medicine Satoki Kusakabe Okayama University Medical School Faculty of Medicine Okayama Japan Ryo Nakamichi Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Aki Yoshida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Keiichiro Nishida Locomotive Pain Center, Okayama University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background and Aim: Psoriasis is a skin disorder complicated by arthritis and enthesitis. The cytokines interleukin (IL)-17, IL-23, and tumor necrosis factor (TNF)-α are reportedly key effectors of psoriasis. Additionally, gamma delta (γδ) T cells exacerbate inflammation by producing inflammatory cytokines such as IL-17 and TNF-α. However, details regarding the mechanisms linking pathogenesis and mechanical stress remain unclear. This study aimed to investigate the effect of strenuous exercise on the pathology of psoriasis using mouse models of imiquimod (IMQ)-induced psoriasis. Methods: Twenty mice were randomly assigned to four groups: IMQ − TRED− (control), IMQ − TRED+ (treadmill running mice), IMQ + TRED− group (IMQ treated mice), and IMQ + TRED+ group (IMQ treated and treadmill running mice). The tissue sections from back skin and thymus were immunostained with antibodies against IL-17, IL-23, and γδ T cells. Shoulder sections were stained using hematoxylin and eosin, and Toluidine Blue and Picrosirius Red. Additionally, the shoulder tissue sections were immunostained with antibodies against TNF-α and matrix metalloproteinase (MMP)-13. Serum cytokine level was measured to evaluate systemic inflammation. Results: Strenuous exercise exacerbated pathological changes associated with psoriasis, including increased γδ T cell infiltration and upregulated IL-17 and IL-23 expression in the skin, as well as enhanced γδ T cell development and IL-17 expression in the thymus. Although strenuous exercise did not further worsen the modified PASI scores, histological and immunological markers of inflammation were significantly enhanced. Serum levels of TNF-α and IL-17 were significantly elevated in IMQ-induced psoriasis model mice. Moreover, pathological changes induced by strenuous exercise were observed in the enthesis, including angiogenesis and upregulated expression of TNF-α and MMP-13. Conclusion: This study revealed that strenuous exercise exacerbates pathological changes in IMQ-induced psoriasis model mice. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2572-1143 9 1 2026 Mechanosensitive Ion Channel PIEZO1 Suppresses BMP2-Induced Ossification of the Annulus Fibrosus Cells e70168 EN Hisakazu Shitozawa Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Nakamichi Department of Orthopaedic Surgery, Okayama University Graduate School Medicine, Dentistry, and Pharmaceutical Sciences Aki Yoshida Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masataka Ueda Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Taichi Saito Department of Orthopaedic Surgery, Okayama University Hospital Koji Uotani Department of Orthopaedic Surgery, Okayama University Hospital Yoshiaki Oda Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryo Takatori Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazutaka Yamashita Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objective: Major cause of low-back pain is intervertebral disc degeneration (IVDD), with mechanical stress playing a crucial role in its progression. A mechanosensitive ion channel, PIEZO1, is involved in various musculoskeletal tissues, but its role in the annulus fibrosus (AF) remains unclear. This study aimed to elucidate the function of PIEZO1 in AF cells under mechanical stimulation. Methods: Primary rat AF cells were subjected to cyclic tensile strain (CTS) at low (2%) and high (12%) strain levels to investigate strain-dependent effects on osteogenic gene expression. We evaluated the effects of Piezo1, Piezo2, and Trpv4 knockdown by RNA interference to identify the upstream mechanotransducer. Furthermore, PIEZO1 was activated using the agonist Yoda1, followed by RNA-sequencing analysis and evaluation of its effects on BMP2-induced osteogenesis in rat AF cells. We also examined the effects of Yoda1 in primary human AF cells. Results: Low-strain CTS significantly suppressed osteogenic marker expression, which was not observed with high strain. Piezo1 knockdown reversed this suppression, whereas Piezo2 and Trpv4 had no effect. Piezo1 activation by Yoda1 produced similar anti-osteogenic effects in both rat and human AF cells. RNA sequencing revealed the enrichment of ossification and calcineurin signaling pathways in rat cells. Furthermore, Piezo1 activation inhibited BMP2-induced osteogenesis and nuclear translocation of p-Smad1/5/9. Conclusions: Piezo1 maintains AF cell homeostasis under mechanical stress by suppressing osteogenic changes via calcineurin-mediated inhibition of BMP signaling, which may represent a novel therapeutic target for IVDD. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1462-8910 27 10 2025 D3 lymph node dissection in colon cancer patients aged 90 years and over: Is it justified? A multi‐institutional retrospective study e70269 EN Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Hospital Satoe Takanaga Department of Gastroenterological Surgery, Okayama University Hospital Ryo Inada Department of Surgery, Kochi Health Sciences Center Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Toshiaki Toshima Department of Surgery, Kagawa Rosai Hospital Tsuyoshi Ohtani Department of Surgery, Saiseikai Okayama Hospital Ryosuke Yoshida Department of Surgery, Okayama Rosai Hospital Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Hospital Setouchi Colorectal Neoplasm Registration study group collaborators Aim: The oncological benefit of D3 lymph node dissection (D3 LND) for colon cancer in patients aged ≥90 years remains unclear. This study aimed to evaluate the impact of D3 LND on outcomes in this specific, vulnerable population. Method: This retrospective cohort study evaluated 166 patients aged ≥90 years with pathological Stages II–III colon cancer undergoing non-D3 or D3 LND from a multicentre database (2011–2022). Postoperative complications, overall survival and cancer-specific survival were compared between LND groups using propensity score-weighted analyses. Results: D3 LND group had significantly more females and laparoscopic procedures. Operation time was longer, and blood loss was lower in the D3 LND group. Postoperative complications and severe complications were significantly fewer, and postoperative hospital stay was shorter in the D3 LND group. The number of harvested lymph nodes and distal margin was significantly higher in the D3 group. While unadjusted analysis showed better overall survival with D3 LND (p < 0.001), adjusted cancer-specific survival showed no significant difference (p = 0.10). Adjusted mortality risk was significantly higher in the non-D3 group (p = 0.001). Conclusion: In nonagenarian colon cancer patients, D3 LND is safe and feasible without increasing complications, but lacks survival benefit. Careful consideration is warranted, and high-quality D2 LND must be consistently ensured when limited surgery is chosen. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0385-5600 2026 Overexpression of Escherichia coli yaiX Confers Multidrug Resistance and Enhances Virulence in the Silkworm Infection Model EN Kinuka Hongu Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuya Ishikawa Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoki Kosaki Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin‐Ichi Miyoshi Research Center for Intestinal Health Science, Okayama University Kazuyuki Furuta Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chikara Kaito Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The emergence of bacteria with both antimicrobial resistance and high virulence has become a global health concern, underscoring the urgent need to elucidate the molecular basis underlying these traits. Here, we employed the silkworm (Bombyx mori) infection model, which is suitable for high-throughput screening, together with an Escherichia coli library containing plasmid clones of all genes from strain W3110, to identify genes whose overexpression enhances virulence. We found that overexpression of the uncharacterized protein YaiX promoted bacterial proliferation in silkworms and increased host lethality. Compared with the empty-vector control, the YaiX-overexpressing strain exhibited resistance to multiple antimicrobial agents with diverse mechanisms of action, including β-lactams, tetracyclines, fluoroquinolones, aminoglycosides, cationic surfactants, and hydrogen peroxide. Sequence analysis revealed that amino acids 18–52 of YaiX contain a transferase hexapeptide domain predicted to form a left-handed parallel β-helix. Overexpression of YaiX mutants lacking regions outside this domain conferred ampicillin resistance, whereas deletion of the hexapeptide domain abolished this phenotype. RNA sequencing and GO enrichment analyses further indicated that YaiX overexpression altered the expression of genes encoding RNA-binding proteins and porins. These findings suggest that YaiX overexpression, through its hexapeptide domain, modulates gene expression and contributes to both multidrug resistance and enhanced virulence in E. coli. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0964-2633 70 3 2025 Prevalence and Modifiable Risk Factors of Dementia in People With Down Syndrome: Cross‐Sectional Study of Japan in Collaboration With the Intellectual Diversity for Goodness Research Consortium (INDIGO‐2019) 329 336 EN Shintaro Takenoshita Department of Neuropsychiatry, Okayama University Hospital Seishi Terada Department of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomokazu Inoue Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Taku Kurozumi Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Manabu Takaki Department of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryozo Kuwano Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Shigeru Suemitsu Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Background: People with Down syndrome (DS) have a strong genetic predisposition to Alzheimer's disease (AD). However, the clinical burden and associated risk factors in diverse, non-Western populations remain less understood. This study aimed to investigate the prevalence of dementia in Japanese adults with DS and to identify modifiable clinical factors associated with dementia. Methods: This cross-sectional multicentre study surveyed 133 adults with DS (mean age 50.1 years) residing in 45 welfare facilities across Japan in 2019. Dementia was diagnosed by a consensus panel of physicians using established criteria (DSM-5, ICD-10, DC-LD) after comprehensive assessments, including the Japanese version of the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID-J). Logistic regression analysis was performed to identify factors independently associated with dementia. Results: Forty-six participants (34.6%) were diagnosed with dementia. The prevalence rose sharply with age: 0% in their 30s, 30.8% in their 40s, 31.6% in their 50s and 65.5% in their 60s. After adjusting for covariates, older age, female sex, dyslipidaemia and visual impairment were independently associated with dementia. Conclusions: This study, the largest of its kind in Asia, confirms a high prevalence of dementia in institutionalized Japanese adults with DS. Crucially, this study is the first to identify dyslipidaemia and visual impairment as independent and potentially modifiable risk factors in this population. These findings highlight tangible targets for clinical interventions aimed at mitigating dementia risk in people with DS. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2574-173X 46 1 2026 Lifestyle Factors and Current Alcohol Consumption Among Japanese Adolescents During the COVID-19 Pandemic: A Nationwide Cross-Sectional Study e70089 EN Masatake Nishiwaki Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hideyuki Kanda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Keita Yoshida Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Aya Kinjo Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University Yuki Kuwabara Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University Hongja Kim Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University Aya Imamoto Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University Hisashi Yoshimoto Department of Family Medicine, General Practice and Community Health, Institute of Medicine, University of Tsukuba Teruna Ito Department of Food and Nutrition, Koriyama Women's University Hideaki Kasuga Department of Hygiene and Preventive Medicine, Fukushima Medical University Ruriko Minobe National Institute of Alcoholism, Kurihama National Hospital Hitoshi Maesato National Institute of Alcoholism, Kurihama National Hospital Maki Jike Department of Food Science and Nutrition, Faculty of Life and Environmental Science, Showa Women's University Yuichiro Otsuka Division of Public Health, Department of Social Medicine, Nihon University School of Medicine Osamu Itani Division of Public Health, Department of Social Medicine, Nihon University School of Medicine Yoshitaka Kaneita Division of Public Health, Department of Social Medicine, Nihon University School of Medicine Susumu Higuchi National Institute of Alcoholism, Kurihama National Hospital Yoneatsu Osaki Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University Background: The COVID-19 pandemic may have influenced drinking behaviors in minors by disrupting daily routines and increasing psychosocial stress, although alcohol use among Japanese adolescents has declined in recent years. We aimed to clarify the relationships between current alcohol consumption and lifestyle factors during the COVID-19 pandemic based on a nationwide cross-sectional survey. Methods: This cross-sectional study analyzed data from the 2021 Lifestyle Survey of Adolescents, a nationwide survey conducted in Japan during the COVID-19 pandemic. A total of 15 549 junior and senior high school students (7645 boys and 7904 girls) were included. Current alcohol consumption was defined as drinking on at least 1 day in the past 30 days. Multivariable logistic regression analyses were used to examine associations between current alcohol consumption and lifestyle factors, including irregular sleep patterns, irregular dietary habits, and increased screen time. Sex-stratified analyses and interaction tests were also performed. Results: The overall prevalence of current alcohol consumption was 2.1%, with slightly higher rates among boys (2.2%) than girls (2.0%). Current alcohol consumption was significantly associated with irregular sleep patterns (odds ratio [OR] = 1.51; 95% confidence interval [CI], 1.17–1.95) and irregular dietary habits (OR = 1.68; 95% CI, 1.18–2.40). An association with increased screen time was also observed (OR = 1.29; 95% CI, 1.00–1.69), particularly among boys. A significant interaction by sex was detected for irregular sleep patterns (p for interaction = 0.013). Conclusions: Alcohol consumption among Japanese adolescents was associated with irregular sleep and dietary habits and, among boys, with increased screen time. These findings highlight the importance of promoting regular routines and addressing lifestyle-related risks to prevent current alcohol consumption among adolescents during public health crises. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1613-6810 21 50 2025 Collagen Signaling via DDR1 Exacerbates Barriers to Macromolecular Drug Delivery in a 3D Model of Pancreatic Cancer Fibrosis e06926 EN Mayu Ohira Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Moe Kitamura Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyo Iwasaki Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haruko Ohta‐Okano Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiyori Tsujii Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Reika Nakamura Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuya Nakazawa Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Akihiro Nishiguchi Biomaterials Field, Research Center for Macromolecules and Biomaterials, National Institute for Materials Science Masaya Yamamoto Department of Materials Processing, Graduate School of Engineering, Tohoku University Kensuke Osada Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Sciences and Technology (QST) Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Horacio Cabral Department of Bioengineering, Graduate School of Engineering, The University of Tokyo Atsushi Masamune Division of Gastroenterology, Graduate School of Medicine, Tohoku University Mitsunobu R. Kano Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Hiroyoshi Y. Tanaka Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fibrosis is a significant barrier to drug delivery in pancreatic ductal adenocarcinoma (PDAC) and contributes to its dismal prognosis. Pancreatic stellate cells (PSCs) drive fibrosis by excessively secreting extracellular matrix proteins such as collagen I. Collagen I is thought to physically obstruct the delivery of macromolecules, such as albumin, antibodies, and nanomedicines. Apart from its structural role, collagen signals through dedicated cell surface receptors, such as the discoidin domain receptors (DDR) 1/2. However, whether and how collagen signaling contributes to fibrotic barrier generation remains uncharacterized. Here, a 3D culture model of PDAC fibrosis constructed from patient PSCs is used to assess the contribution of DDR1/2-mediated collagen signaling. DDR1/2 inhibition diminishes collagen I expression in PSCs to enhance macromolecular delivery. Moreover, MEK inhibitors exacerbate the fibrotic barrier by up-regulating collagen I, an effect reversed by inhibiting DDR1/2. Through isoform-specific targeting, inhibiting DDR1, but not DDR2, is shown to be effective. Downstream of DDR, the involvement of the PI3K/AKT/mTOR pathway is demonstrated, particularly alternative mTOR complexes involving MEAK7 and GIT1. Altogether, the results show in vitro that DDR1-mediated collagen signaling exacerbates the fibrotic barrier and may be targeted to enhance macromolecular drug delivery in PDAC. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2688-4526 7 2 2026 Safety and efficacy of Rezūm water vapour energy therapy in BPH patients receiving antithrombotic therapy: A Japanese single‐centre experience e70170 EN Takatoshi Moriwake Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Tominaga Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Katayama Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haruki Kaku Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ichiro Tsuboi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kasumi Yoshinaga Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoaki Yamanoi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsushi Kawada Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuya Sadahira Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takehiro Iwata Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shingo Nishimura Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kensuke Bekku Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuhiro Katayama Department of Urology, Okamura Isshindo Hospital Motoo Araki Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: The objective of this study is to evaluate the safety and efficacy of Rezūm water vapour energy therapy (WAVE) in Japanese patients with benign prostatic hyperplasia (BPH) continuing antithrombotic therapy and to validate the Okayama University Modified Clavien-Dindo classification (OU-mCD) for perioperative hematuria. Patients and Methods: We retrospectively analysed 80 consecutive patients who underwent WAVE from August 2023 to July 2024, including 37 (46.2%) continuing antithrombotic therapy perioperatively. Hematuria within 30 days was graded using conventional Clavien-Dindo classification and the OU-mCD, a novel classification focusing on intervention necessity. We assessed clinically significant hematuria (Grade ≥ Ib), catheter-free rate, prostate volume reduction and haemoglobin change. Results: Clinically significant hematuria occurred in 21.6% (8/37) of patients continuing antithrombotic therapy versus 4.7% (2/43) without (p = 0.038). All 10 Grade ≥ Ib cases occurred during hospitalization with the catheter in place and were managed conservatively with continuous bladder irrigation (median 1 day); none required transfusion or surgical reintervention. Only one patient required temporary drug discontinuation. Treatment efficacy did not differ by antithrombotic status: 86.2% achieved PVR < 50 ml with 44% mean prostate volume reduction. Multivariate analysis identified antithrombotic therapy as the sole independent risk factor for Grade ≥ Ib hematuria (OR 5.46, 95% CI 1.06–28.16, p = 0.042). Conclusion: WAVE can be safely performed with continued antithrombotic therapy. Whereas Grade ≥Ib hematuria occurred in 25% of antiplatelet/anticoagulant users (vs. 5% without), 75% had no significant bleeding, and all complications were managed conservatively without transfusion. The OU-mCD provides precise complication stratification. These findings suggest outpatient procedures may be feasible with appropriate patient selection. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0309-0167 88 5 2025 Claudin-18 expression in gastric type adenocarcinoma and HPV-associated adenocarcinoma of the uterine cervix 1003 1015 EN Nobuko Yasutake Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Yuki Yokawa Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Takehiro Tanaka Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Riri Mishima Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Misato Komamizu Department of Gynecology and Obstetrics, Graduate School of Medical Sciences Kyushu University Fukuoka Japan Ryosuke Kuga Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University Rina Jiromaru Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University Shinichiro Kawatoko Department of Medicine and Clinical Science, Kyushu University Beppu Hospital Kenzo Sonoda Department of Gynecology, Kyushu University Beppu Hospital Hideaki Yahata Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Kiyoko Kato Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Yoshinao Oda Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University Hidetaka Yamamoto Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Aims: Claudin-18 (CLDN18) is both a marker for the gastric phenotype and a therapeutic target. However, little is known about its immunoexpression in endocervical adenocarcinomas (ECAs), particularly as detected using the clone 43-14A antibody, or about the gene expression of its isoforms in ECAs. Methods and results: We examined CLDN18, HIK1083, p16 and Rb expression by immunohistochemistry and high-risk human papillomavirus (HR-HPV) mRNA by in situ hybridization (ISH) in 121 ECAs, including 35 HPV-independent adenocarcinomas (gastric type [GAS], n = 24; non-GAS, n = 11) and 86 HPV-associated ECAs. We also analysed mRNA expression of the CLDN18.1 (lung type) and CLDN18.2 (gastric type) isoforms by quantitative polymerase chain reaction (qPCR) in selected cases. CLDN18 positivity was detected in 8/24 (33%) GASs, 0/11 (0%) non-GASs and 2/86 (2%) HPV-associated ECAs, with positivity defined as staining in ≥75% of tumour cells, as in gastric cancer. When a 5% cut-off was used, CLDN18 positivity was detected in 22/24 (92%) GASs, 0/11 (0%) non-GASs and 6/86 (7%) HPV-associated ECAs; CLDN18 expression was thus significantly associated with GAS histology (P < 0.0001). Among the 6 cases of HPV-associated ECAs with CLDN18 expression (ranging from 5% to 80%), the histological patterns included a mix of usual and mucinous features in 4 cases, pure usual type in 1 and villoglandular variant in 1. Otherwise features such as p16 overexpression and the Rb partial loss pattern were consistent with those of HPV-associated ECAs. Six of 22 (27%) CLDN18-positive GASs were also positive for p16, but their other features—such as CLDN18 expression and the Rb preserved pattern—were the same as in p16 negative GASs. Expression of CLDN18.2 mRNA but not CLDN18.1 mRNA was confirmed in both GASs and HPV-associated ECAs. Conclusions: CLDN18 (43-14A) emerged as a potential diagnostic and therapeutic marker for GAS. A minor subset of HPV-associated ECAs also can be immunoreactive for CLDN18 and express CLDN18.2 mRNA, suggesting divergent gastric phenotypic differentiation. The caution is that GAS and HPV-associated ECAs can share overlapping histological features and similar expression of CLDN18 and p16. 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.

Wiley Acta Medica Okayama 2577-171X 9 2 2026 Mitrofanoff Appendicovesicostomy With Boari Flap for Complete Female Urethral Transection: A Case Report e70154 EN Kohei Mori 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 Tatsushi Kawada 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 Yusuke Tominaga 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 Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuichiro Yamasaki Department of Urology, Kanagawa Children's Medical Center Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction: Female urethral complete transection caused by pelvic trauma is extremely rare, and no standard management has been established when urethral reconstruction is not feasible. Case Presentation: A woman in her twenties sustained an open pelvic fracture with perineal injury due to a traffic accident. Complete urethral transection was identified, and a suprapubic cystostomy was placed. After staged vaginal reconstruction and bladder function evaluation, a Mitrofanoff appendicovesicostomy was performed. Because the appendix was not enough to reach the umbilicus, a Boari flap was created to compensate for the length. Urodynamic evaluation showed improvement from a preoperative high-pressure bladder to increased compliance postoperatively, though pharmacological management was still required. Postoperatively, the patient achieved stable clean intermittent catheterization without complications. Conclusion: The Mitrofanoff procedure can be an effective option in female urethral injuries where reconstruction is impossible. The addition of a Boari flap may expand its applicability by overcoming conduit length limitations. 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. Methods: Literature focusing on surgical treatment for older cancer patients was extracted from Japanese clinical practice guidelines for gastric cancer, lung cancer, colorectal cancer, liver cancer, and gynecological cancers (uterine body, uterine cervix, ovary, and external genitalia and vagina). Outcomes were reviewed, and committee members determined the strength of evidence on a four-point scale (A to D), with A being the highest and D being the lowest. Results: Older cancer patients tend to have a higher incidence of postoperative complications and postoperative syndromes, and their expected survival is generally shorter compared to non-older patients. When extensive surgeries such as para-aortic lymph node dissection and/or resection with other organs are performed for older cancer patients, the postoperative mortality rates tend to increase compared to non-older patients. Conclusion: Surgical treatments for older cancer patients tend to result in higher morbidity even when the patients are in good health status. Nevertheless, there is still a possibility that a certain fraction of the patients achieve treatment outcomes comparable to those of non-older patients. Therefore, surgical indication and procedure for older cancer patients should be carefully determined based on surgical invasiveness and patient tolerability. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1758-5902 18 1 2025 Metachronous Pancreatic Metastasis of Myxoid Liposarcoma Successfully Treated With Robotic Spleen‐Preserving Distal Pancreatectomy With Splenic Vessels Resections: A Case Report e70069 EN Yumi Sota 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 Motohiko Yamada 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 Kazuya Yasui 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 Noriyuki Kanehira Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akari Masunaga 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 Pancreatic metastasis of myxoid liposarcoma (MLS) after primary resection is extremely rare. Herein, we present a case of metachronous pancreatic metastasis of MLS that was successfully treated with robotic spleen-preserving distal pancreatectomy (SPDP) using the Warshaw technique. A 60-year-old woman underwent radical resection of a 25-cm MLS in the right thigh after receiving neoadjuvant radiotherapy. The patient developed a 6-cm solitary pancreatic metastasis of the MLS 2 years later. Because no other distant metastases were detected, robotic SPDP (Warshaw technique) was performed. The operative time was 140 min with minimal blood loss. Follow-up at 3 months showed no recurrence. To our knowledge, this is the first report of a case of metachronous pancreatic metastasis of MLS successfully treated with robotic SPDP. Curative resection using minimally invasive surgery should be performed for solitary pancreatic metastases from MLS. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 14 2 2026 Oculogyric Crisis During Chronic Aripiprazole Therapy: A Diagnostic Challenge in the Emergency Department e72067 EN Kohei Tokioka Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama Universitye, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Okayama University Japan Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Ippei Matsuo Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Oculogyric crisis can occur even during chronic, stable aripiprazole therapy without recent dose escalation. In patients with acute upward eye deviation and an otherwise normal neurologic examination, medication review is key to recognizing drug-induced dystonia and avoiding unnecessary neurologic workup. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0007-1188 2026 Induction of IL-9-producing CD8+ T cells by ascochlorin derivatives EN Natsumi Imano Department of Immunology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Mikako Nishida Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Miho Tokumasu Department of Immunology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Weiyang Zhao Department of Immunology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Nahoko Yamashita Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Heiichiro Udono Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Background and Purpose: Ascochlorin (ASC) is an antiviral antibiotic from the fermented broth of Ascochyta viciae which exerts an inhibitory effect to cancers. Its impact on immune cells has not been examined. In this study, we obtained ASC derivatives with less cytotoxicity and determined whether they affected T cells, indicating possible immune-mediated antitumour effects. Experimental Approach: Newly synthesised ASC derivatives were screened for inhibitory effects on T-cell antigen receptor (TCR)-stimulated proliferative responses using murine CD4+ and CD8+ T cells. Two compounds were identified that exhibited >10-fold less toxicity compared with ASC. N184, the less toxic of the two, was analysed for its in vivo antitumour effects, and in vitro effects on CD8+ T-cell proliferation, survival, cytokine production and exhaustion, using microscopy, qPCR and flow cytometry. Key Results: N184 induced limited IL-9 production in CD8+ T cells following TCR stimulation, thereby improving cell survival. It also enhanced cytokine production in the late phase of proliferation and suppressed the induction of exhaustion. N184 suppressed tumour growth in mice in a CD8+ T cell-dependent manner. The effect was partially prevented by an IL-9-neutralising antibody. Conclusion and Implications: N184 induces differentiation of IL-9-producing CD8+ T cells in vitro and elicits antitumour immunity in an IL-9-dependent manner. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Time Course of the Development and Loss of Delta-9-tetrahydrocannabinol Tolerance: Effects on Hypothermia and Spontaneous Locomotor Activity in Mice 47 54 EN Yukiomi Eguchi Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Soichiro Ushio Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Keiichi Irie Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Yuta Yamashita Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Miyu Eguchi Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Takafumi Nakano Department of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Kenichi Mishima Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Original Article 10.18926/AMO/70072 Deregulation of cannabis use is gradually expanding in Europe and the United States. However, the biological processes driving tolerance to delta-9-tetrahydrocannabinol (Δ9-THC), the main psychoactive component of cannabis, remain unclear. Thus, this study aimed to investigate the mechanisms and time course of tolerance development and loss to Δ9-THC in mice. Male ICR mice (7 weeks old) were administered Δ9-THC once daily for 3 days and then divided into three groups according to the washout period (3-, 10-, and 17-day washout groups). After each washout, changes in body temperature and locomotor activity were measured following re-exposure to Δ9-THC. Furthermore, the mRNA expression levels of CB1 and CB2 receptors in the brain were evaluated using real-time PCR. On day 1, significant hypothermia and reduced spontaneous locomotor activity were observed in the Δ9-THC-treated mice compared with the vehicle-treated mice. Tolerance to the hypothermic and locomotor-suppressing effects of Δ9-THC developed on days 2 and 3, respectively, and dissipated after 3 and 11 days of washout, respectively. These differences in the rates of tolerance development and recovery may reflect distinct underlying mechanisms. No significant changes in receptor mRNA expression were observed. These findings highlight the complexity of Δ9-THC tolerance and its potential implications for long-term cannabis use. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0001-690X 153 3 2026 Impact of Schizophrenia Spectrum Disorders on the Receipt of Invasive and Systemic Therapy for Colorectal Cancer: A Nationwide Multicenter Retrospective Cohort Study in Japan 191 199 EN Masaki Fujiwara Department of Neuropsychiatry, Medical Development Field, Okayama University Yuto Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Taisuke Ishii Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center Tomone Watanabe Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center Maiko Fujimori Division of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer Center Naoki Nakaya Tohoku Medical Megabank Organization, Tohoku University Toshihiko Kawamura Department of Medical Informatics, Shimane University Hospital Koji Otsuki Department of Psychiatry, Faculty of Medicine, Shimane University Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Medical Development Field, Okayama University Taichi Shimazu Division of Behavioral Sciences, National Cancer Center Institute for Cancer Control, National Cancer Center Shiro Hinotsu Department of Biostatistics and Data Management, Sapporo Medical University Yosuke Uchitomi Department of Cancer Survivorship and Digital Medicine, The Jikei University School of Medicine Masatoshi Inagaki Department of Psychiatry, Faculty of Medicine, Shimane University Introduction: This study examined treatment disparities for colorectal cancer among patients diagnosed with schizophrenia spectrum disorders (SSD), focusing on invasive treatments and stage-appropriate systemic therapy within a universal healthcare system. Method: In this nationwide retrospective cohort study (2018–2021), we identified 248,966 colorectal cancer patients, including 2337 diagnosed with SSD, using linked cancer registry and insurance claims data in Japan. The presence of SSD was classified according to ICD-10 codes F20–29. We used multivariable logistic regression to compare the odds of receiving stage-appropriate adjuvant chemotherapy and systemic therapy, as well as the odds of receiving surgical or endoscopic treatments, between the two groups. The analysis adjusted for age, sex, clinical stage, and scores on the Charlson Comorbidity Index and Barthel Index. Results: The clinical stage distribution at diagnosis for colorectal cancer differed significantly between patients with SSD and those without psychiatric disorders (p < 0.001). After adjusting for clinical stage and other covariates, patients with SSD demonstrated significantly lower odds of receiving surgical or endoscopic treatment (adjusted odds ratio [aOR], 0.83; 95% CI, 0.73–0.94). The disparities were more pronounced for systemic therapy; patients with SSD had substantially lower odds of receiving adjuvant chemotherapy for stage III disease (aOR, 0.33; 95% CI, 0.26–0.41) and systemic therapy for stage IV disease (aOR, 0.23; 95% CI, 0.17–0.31). Conclusion: Patients with SSD encounter substantial disparities in accessing standard colorectal cancer care, particularly systemic therapies. These findings highlight the urgent need for interventions to ensure equitable cancer treatment for this vulnerable population. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2769-2558 5 1 2026 Cardiogenic cerebral infarction after Takotsubo cardiomyopathy in a patient with catatonia: A case report e70285 EN Masaki Fujiwara Department of Neuropsychiatry, Medical Development Field, Okayama University Yuto Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Osawa Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center Shinji Sakamoto Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Kodama Okayama Psychiatric Medical Center Background: Takotsubo cardiomyopathy (TTC) is a transient cardiac condition often triggered by an emotional or physical stress. TTC usually has a benign clinical course with full recovery. However, in rare cases, TTC is complicated by cardiogenic shock, left ventricular rupture, or ventricular thrombus. We report a case of a patient with catatonia who developed TTC and subsequently experienced extensive cerebral infarction. Case Presentation: A 71-year-old woman with no prior psychiatric history was admitted for catatonia following a suicide attempt. During hospitalization, she exhibited electrocardiography (ECG) abnormalities and elevated D-dimer levels. Transthoracic echocardiography revealed apical hypokinesis and basal hyperkinesis, consistent with TTC, along with an intraventricular thrombus. Cardiovascular CT angiography confirmed normal coronary arteries. She was diagnosed with TTC complicated by left ventricular thrombus and deep vein thrombosis. Anticoagulant therapy was initiated. Despite improvement in catatonia with lorazepam, she developed right hemiplegia and aphasia on Day 5 due to cardiogenic cerebral infarction from thromboembolism. Thrombolytic therapy was not indicated, and conservative treatment was provided. Although cardiac function normalized by Day 16, she was left with severe neurological deficits. Conclusion: The case highlights the diagnostic challenges of TTC in non-communicative psychiatric patients and the potential for severe complications. Psychiatrists need to be aware of the development of TTC as a serious physical complication in patients with catatonia. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0028-646X 2026 Starch Synthase 3 isoforms are essential for normal starch granule initiation in wheat endosperm EN Jinjin Ding John Innes Centre, Norwich Research Park Brendan Fahy John Innes Centre, Norwich Research Park Ryo Matsushima Institute of Plant Science and Resources, Okayama University Qiantao Jiang State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Triticeae Research Institute, Sichuan Agricultural University David Seung John Innes Centre, Norwich Research Park No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0031-9317 178 1 2026 Reactive Carbonyl Species Mediate Isothiocyanate Signaling Pathway in Arabidopsis thaliana Guard Cells e70775 EN Sumaiya Farzana Graduate School of Environmental and Life Science, Okayama University Md. Moshiul Islam Graduate School of Environmental and Life Science, Okayama University Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Jun'ichi Mano Science Research Center, Yamaguchi University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Our previous results demonstrated that depletion of glutathione (GSH) rather than elevation of levels of reactive oxygen species (ROS) is highly correlated with the decrease in stomatal aperture induced by isothiocyanates (ITCs), although ROS is considered a key second messenger in stomatal closure, suggesting that another signal component regulates stomatal apertures along with GSH depletion. This study, using Arabidopsis, clarified that reactive carbonyl species (RCS), especially acrolein and 4-hydroxy-(E)-2-nonenal, are determinants of stomatal aperture responses to ITCs. All tested ITCs, allyl isothiocyanate (AITC), sulforaphane (SFN), benzyl isothiocyanate (BITC), and phenethyl isothiocyanate (PEITC), significantly induced stomatal closure, which was inhibited by the RCS scavengers, carnosine and pyridoxamine. The RCS scavengers suppressed ITC-induced depletion of GSH but not elevation of ROS levels. All tested ITCs (AITC, SFN, BITC, and PEITC) increased levels of RCS and non-RCS aldehydes in the epidermal tissues. However, acrolein, 4-hydroxy-(E)-2-nonenal, crotonaldehyde, and (E)-2-pentenal induced stomatal closure at 10 and 100 μM, whereas propionaldehyde, butyraldehyde, and n-pentanal did not at concentrations up to 100 μM. Acrolein and 4-hydroxy-(E)-2-nonenal more effectively induced stomatal closure and GSH depletion than crotonaldehyde and (E)-2-pentenal did. The contents of RCS were more strongly correlated with GSH levels and stomatal closure than with ROS levels. These results suggest that RCS, especially acrolein and 4-hydroxy-(E)-2-nonenal, acts as key regulators of stomatal closure in guard cells in response to ITCs. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1521-6543 65 4 2013 Synthesis of biopterin and related pterin glycosides 300 309 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Hiroshi Yamamoto School of Pharmacy, Shujitsu University Certain pterins having a hydroxyalkyl side chain at C-6 have been found as glycosidic forms in certain prokaryotes, such as 2′-O-(α-D-glucopyranosyl)biopterin from various kinds of cyanobacteria, and limipterin from a green sulfur photosynthetic bacterium. Synthetic studies on glycosides of biopterin and related pterins have been made in view of the structural proof as well as for closer examination of their biological activities and functions. The syntheses of these natural pterin glycosides have effectively been achieved, mostly through appropriately protected N2-(N,N-dimethylaminomethylene)-3-[2-(4-nitrophenyl)ethyl]pterin derivatives as glycosyl acceptors, and are reviewed here. © 2013 IUBMB Life 65(4):300–309, 2013. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0041-1132 2026 Pediatric autologous peripheral blood stem cell collection without heparin using a highly concentrated sodium citrate anticoagulant: A retrospective comparison with standard ACD-A EN Keiko Fujii Department of Hematology, Okayama University Hospital Wataru Kitamura Department of Hematology, Okayama University Hospital Kana Washio Department of Pediatrics, Okayama University Hospital Kazuhiro Ikeuchi Department of Hematology, Okayama University Hospital Joji Shimono Department of Hematology, Okayama University Hospital Hiroyuki Murakami Department of Hematology, Okayama University Hospital Fumio Otsuka Division of Clinical Laboratory, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Okayama University Hospital Nobuharu Fujii Department of Hematology, Okayama University Hospital Background: Heparin combined with sodium citrate has been used in leukocytapheresis for pediatric patients. Since 2022, we have performed leukocytapheresis using a highly concentrated sodium citrate solution (HSC, 5.32%) instead of acid citrate dextrose solution A (ACD-A). We conducted this study to determine whether HSC use reduces run time and the total amount of anticoagulant solution in children. Study Design and Methods: We retrospectively analyzed data from consecutive autologous peripheral blood stem cell harvests (auto-PBSCHs) between June 2012 and May 2025, including patient characteristics, mobilization methods, protocol used, anticoagulant type, run time, total anticoagulant solution volume, and collection efficiency. Results: Auto-PBSCH was performed using the mononuclear cell collection (MNC) protocol in 28 procedures and the continuous MNC protocol in 20 procedures. ACD-A was used in 35 procedures and HSC in 13. The run time was significantly shorter (204 [range, 117–302] vs. 157 min [range, 103–227], p = .02) in the HSC group and also confirmed in multivariable regression analysis (coefficient, −55.6; 95% confidence interval, −106.2 to −5.04; p = .03). In a subgroup analysis of cMNC procedures, CD34+ collection efficiency showed a strong negative correlation with the proportion of run time devoted to establishing the initial interface (r = −.73, p = .0003). Conclusion: Delays in establishing the initial interface can reduce the duration of the effective MNC collection phase and may negatively affect collection efficiency. Careful attention to the initial interface phase is therefore warranted when using HSC. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0022-152X 62 12 2025 An Improved Synthesis of a Key Intermediate for Glycosylation of Biopterin and Its Application for the First Synthesis of Microcystbiopterin B 2021 2029 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Yuta Maeda Department of Chemistry, Faculty of Science, Okayama University Katsuya Iwasaki Department of Chemistry, Faculty of Science, Okayama University A key intermediate for the selective 2′-O-glycosylation of biopterin, N2-(N,N-dimethylaminomethylene)-1′-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]biopterin (12), was efficiently synthesized via a novel route starting from d-glucose, leading to an improved overall yield. This new pathway involves the preparation of a 5-deoxy-l-arabinose phenylhydrazone derivative (9) as a crucial intermediate in the construction of the pteridine ring. Utilizing compound 12, the first synthesis of microcystbiopterin B (4) was accomplished by glycosylation of 12 with 4,6-di-O-acetyl-2-O-(4-methoxybenzyl)-3-O-methyl-α-d-glucopyranosyl bromide (19) in the presence of silver triflate and tetramethylurea, followed by stepwise deprotection. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0022-3492 2026 A retrospective cohort study comparing periodontal regeneration using fibroblast growth factor‐2 versus autologous bone graft EN Toshiki Matsumoto Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin Nakamura Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Ito‐Shinoda Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mai Sakamoto 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 Yasuki Nonomura Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidetaka Ideguchi Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Okubo Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Kazu Takeuchi‐Hatanaka Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Kazuhiro Omori Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yamamoto The Center for Graduate Medical Education (Dental Division), Okayama University Hospital Shogo Takashiba Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Fibroblast growth factor-2 (FGF-2) is a novel agent utilized in periodontal regeneration therapy. However, its clinical efficacy compared with autologous bone graft (ABG), a long-established treatment, remains unclear. This study aimed to compare the clinical outcomes of FGF-2 and ABG and to assess the impact of patient background factors on outcomes when using FGF-2. Methods: We collected the subjects from January 2013 to September 2023. Clinical outcomes included the vertical bone defect improvement rate (VBDIR) and the probing pocket depth improvement (PPDI). Clinical outcomes between the two groups were compared using analysis of covariance (ANCOVA), adjusting for age, sex, smoking history, and hypertension. Additionally, a multilevel linear analysis was performed to assess factors influencing outcomes in FGF-2. Results: A total of 180 sites from 141 patients (FGF-2: 150 sites; ABG: 30 sites) were evaluated. Both VBDIR and PPDI significantly improved postoperatively in both groups. There were no significant differences in clinical outcomes between FGF-2 and ABG. In FGF-2, smoking history was positively associated, while the preoperative bone defect angle (BDA) was negatively associated with clinical outcomes. Conclusions: FGF-2 might exhibit clinical outcomes comparable to those of ABG, suggesting it is a clinically viable alternative for vertical bone defects. When using FGF-2, patient-specific factors such as smoking history and preoperative BDA should be considered carefully. The name in the trial registry: A survey of clinical practice and evaluation of treatment outcomes of periodontal regenerative therapy using REGROTH at Okayama University Hospital No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1687-8728 2026 1 2026 Experimental Analysis of Automatic Discrimination Performance Between Simulated Bruxism and Non‐Bruxism Under Conscious Conditions Using Electromyography and Machine Learning 7874254 EN Hajime Minakuchi Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuhiro Nagasaki Department of Electrical Engineering and Information Systems, Graduate School of Engineering, The University of Tokyo Lộc Hoàng Đình Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruna Miki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ko Omori Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tazuko Nishimura Department of Electrical Engineering and Information Systems, Graduate School of Engineering, The University of Tokyo Takuo Kuboki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuaki Minematsu Department of Electrical Engineering and Information Systems, Graduate School of Engineering, The University of Tokyo Purpose: This study aimed to evaluate the potential use of machine learning to automatically classify electromyography (EMG) data into bruxism simulated movement with tooth contact (BMwTC), bruxism simulated movement without tooth contact (BMwoTC), and non-bruxism movement (non-BM). Methods: Twelve eligible healthy participants (female/male: 2/10, mean age: 35.3 ± 8.4 years) were asked to perform the simulated movements (all the tasks were performed five times for 5 s each with a 30-s rest interval). The electrodes were placed on the masseter, infrahyoid, inframandibular, and chin muscles. A sound sensor was placed adjacent to the masseter. The EMG and sound data were sampled at 1 and 44.1 kHz, respectively. Single- and multi-stream hidden Markov models (HMMs) were used to automatically discriminate the tested behavior from the others using a hamming window with 100 ms and shift length of 50 ms. The leave-one-out method was used for training and testing the model, with data from 11 participants used for training and one for testing. Each participant was evaluated, and the final performance was measured by averaging the results of 12 classification trials. The validity of the discrimination was assessed by calculating the harmony mean values using six EMG signals and the sound data. Results: The masseter EMG demonstrated significantly higher discrimination accuracy in the single-stream model (p < 0.05, One-way ANOVA, Tukey HDS). The multi-stream model also demonstrated higher accuracy; however, no significant difference was observed. Notably, the accuracy of BMwoTC was less than 0.5. Conclusion: The machine-learning-based discriminative system accurately discriminates BMwTC from non-BM using masseter EMG. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0029-6473 2026 1 2026 Knowledge and Attitudes Toward Pain Management Among Nurses in University-Affiliated Hospitals in Western Japan: A Cross-Sectional Study 9991157 EN Mengyao Xi Graduate School of Health Sciences, Okayama University, Yuki Kajiwara Faculty of Health Sciences, Okayama University Takako Hiramatsu Department of Nursing, Kawasaki Medical School Hospital Michiko Morimoto Faculty of Health Sciences, Okayama University Background: Pain is a major global concern. Nurses’ knowledge and attitudes toward pain management are critical determinants of pain care quality and patient outcomes, making them essential for effective clinical practice. Objective: This study aimed to assess nurses’ pain management knowledge and attitudes using the Japanese version of the Knowledge and Attitudes Survey Regarding Pain (J-KASRP), applied for the first time in Japan, and to examine how background factors affect these aspects. Methods: A descriptive, cross-sectional survey was conducted with 1589 nurses in three university-affiliated hospitals in Western Japan. Data were collected using a questionnaire capturing sociodemographic information and the J-KASRP. Descriptive statistics, t-tests, one-way ANOVA, and effect size were used to analyze J-KASRP scores and subdomains. Tukey’s honestly significant difference test was applied for post hoc comparisons across clinical experience patterns. Results: Of 1001 respondents, 856 valid responses (85.5%) were analyzed. The mean age was 30.1 years (SD = 8.3), and the mean total correct response rate for the J-KASRP was 59.8%; only 1.3% scored ≥ 80%. Cancer-related pain had the lowest J-KASRP subdomain score (42.5%, SD = 20.3%). Higher total J-KASRP scores were found for those with a higher level of education, prior clinical pain education, and recent opioid administration experience (all p < 0.001, effect size > 0.2). In an exploratory pattern analysis, regardless of education level, respondents with both education and opioid administering experience had the highest total and pharmacology subdomains’ scores. No significant differences in cancer-related pain subdomain were observed across patterns of clinical experiences. Conclusions: This first application of the J-KASRP in Japan revealed that nurses’ pain management knowledge and attitudes need to be strengthened, especially for cancer-related pain and opioid pharmacology. The study findings highlight the importance of pain management strengthening education and training to enhance nurses’ evidence-based knowledge and clinical competence. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1758-5902 18 1 2025 A Procedural Transhiatal Approach for the Thoracic Para‐Aortic Lymph Node: A Case Report e70066 EN Masashi Hashimoto 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 Yasushige Takeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hijiri Matsumoto 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 Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The thoracic posterior para-aortic lymph node (TPAN) is classified as an extra-regional lymph node in esophageal cancer, with metastasis indicating poor prognosis. However, some cases with suspected TPAN metastasis may benefit from esophagectomy with lymph node dissection, including TPAN. This report presents the case of a 58-year-old man with upper thoracic esophageal squamous cell carcinoma and suspected simultaneous TPAN metastasis who underwent neoadjuvant chemotherapy followed by thoracoscopic subtotal esophagectomy and procedural transhiatal TPAN dissection. This transhiatal approach provided direct access to the lymph node without additional thoracic incisions, ensuring safe resection in coordination with the assistant and following anatomical landmarks systematically. Pathological examination showed a false-positive TPAN finding, though the patient later developed distant recurrence. Compared with conventional approaches, this transhiatal technique allows for procedural and reproducible lymphadenectomy while minimizing respiratory burden. This case highlights the feasibility of a transhiatal approach for TPAN dissection. 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.

Wiley Acta Medica Okayama 0919-8172 2025 Daytime Bladder Control Status in Toddlerhood Is Associated With Subsequent Bedwetting in Preschool Years: A Nationwide Cohort Study of Over 30 000 Japanese Children EN Takatoshi Moriwake Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naomi Matsumoto Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Tominaga Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kensuke Uraguchi Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoko Kobayashi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ichiro Tsuboi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kasumi Yoshinaga Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoaki Yamanoi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsushi Kawada Department of Urology Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Okayama Japan Takuya Sadahira Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Katayama Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takehiro Iwata Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shingo Nishimura Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kensuke Bekku Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohei Edamura Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soshi Takao Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoo Araki Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: Nocturnal enuresis is common in early childhood. While daytime bladder control typically precedes nighttime continence, the temporal relationship between early daytime bladder control and subsequent bedwetting remains unclear. We investigated whether daytime bladder control status at age 2.5 years—as indicated by diaper use—is associated with bedwetting at age 4.5 years in a Japanese nationwide cohort. Methods: We analyzed data from the Japanese Longitudinal Survey of Newborns in the 21st Century (2010 cohort). Daytime bladder control was assessed at age 2.5 years through caregiver-reported diaper use, and bedwetting frequency at age 4.5 years through parental questionnaires. Modified Poisson regression estimated risk ratios (RRs), adjusting for birth-related factors, socioeconomic status, daycare attendance, and developmental milestones. Results: Among 32 168 children, 26 651 (82.8%) still used diapers at 2.5 years. Bedwetting prevalence at 4.5 years was 42.2%: 34.5% in children who achieved daytime bladder control at 2.5 years versus 43.9% in those still using diapers. After multivariable adjustment, incomplete daytime bladder control at 2.5 years was associated with higher bedwetting risk (adjusted RR 1.25; 95% CI, 1.20–1.31). Multinomial regression revealed dose–response relationships: odds ratios 1.41 (95% CI, 1.30–1.52) for “sometimes” and 1.58 (95% CI, 1.42–1.77) for “often” bedwetting. Conclusions: Daytime bladder control status at 2.5 years was associated with a 25% increased bedwetting risk at 4.5 years. This association likely reflects individual differences in bladder control maturation rather than causal effects. While daytime bladder control may serve as a developmental marker, its validity as an intervention target remains unestablished. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 13 12 2025 Experience and Insight Into Genetic Diagnosis of Infective Aortic Aneurysm e71586 EN Shinnosuke Fukushima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takumi Fujimori Microbiology Division, Clinical Laboratory, Okayama University Hospital Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Culture-negative infected aneurysms possibly occur in various clinical situations, including prior antibiotic exposure. Accurate microbial identification is crucial for an optimal antimicrobial strategy. 16S ribosomal RNA gene sequence analysis would provide a useful tool for precise bacterial identification. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 13 12 2025 Mycobacterium intracellulare-Induced Flexor Tenosynovitisof the Forearm e71698 EN 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 We herein document a clinically challenging case of Mycobacterium intracellulare tenosynovitis in an immunocompromised patient with rheumatoid arthritis. Diagnosing nontuberculous mycobacterial tenosynovitis is often challenging because it often mimics rheumatoid arthritis flares. Combination antimycobacterial therapy combined with surgical intervention is essential for the treatment of this refractory condition. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 13 10 2025 Recurrent Septic Shock in Immunosuppressed Patients e71249 EN Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Koji Fujita Department of General Medicine and Infectious Diseases, Tsuyama Chuo Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Cytomegalovirus gastroenteritis presents with diarrhea and abdominal pain in immunosuppressed patients, and histopathological examination is essential by endoscopy. This case illustrates that cytomegalovirus enteritis may develop insidiously and possibly invoke shock in immunocompromised patients, warranting its inclusion in the differential diagnosis of recurrent septic shock. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2051-3380 13 6 2025 Corynebacterium striatum-Associated Pyogenic Osteomyelitis With Direct Extension From Postoperative Empyema e70230 EN Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Corynebacterium striatum can cause postoperative empyema. C. striatum-associated empyema may be associated with osteomyelitis. Rifampicin is a viable therapeutic option for C. striatum infection. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2575-6265 6 5 2025 Seaweed Extracts Improve Salinity Tolerance in Cereal Crops—A Meta‐Analysis e70094 EN Md. Nuruzzaman Department of Plant Resources, College of Industrial Sciences, Kongju National University Md. Tahjib‐Ul‐Arif Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University Md. Abdul Hannan Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University Yoshiyuki Murata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University M. Afzal Hossain Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University Seaweeds are considered an essential component of the blue economy. Because seaweed extracts are rich in bioactive compounds that enhance plant stress resilience, exploiting this resource could offer a sustainable solution for crop production. Salinity is a major abiotic challenge that significantly impacts crop yield and food security. Through meta-analysis, we explored whether the exogenous application of seaweed extracts improves the salt tolerance of cereal crops. All the studies chosen for this study utilized aqueous seaweed extracts as foliar sprays. A multi-level meta-analysis with a mixed effects model was performed to determine the effect size. This meta-analysis demonstrated that applying aqueous seaweed extracts enhanced the shoot and root biomass under normal and salinity stress conditions, suggesting that seaweed extract can help improve crop stress tolerance. The seaweeds studied belonged to three classes: Phaeophyceae, Rhodophyta, and Chlorophyta, with extracts from Chlorophyta and Phaeophyceae significantly enhancing biomass production under salinity conditions. Applying aqueous seaweed extracts effectively improved salinity tolerance at both 34.2–100 mM and 101–400 mM NaCl equivalent salinity stress. Moreover, exogenous foliar application of ≤ 25% aqueous seaweed extracts was most effective for improving salinity tolerance in cereals. The impact of seaweed extracts on cereal crop yields has not been extensively reported; therefore, further studies should focus on this aspect. 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.

Wiley Acta Medica Okayama 2050-0904 13 2 2025 Maturity-Onset Diabetes of the Young (MODY) With HNF1B p.Glu105Lys Mutation Achieving Significant Insulin Reduction on Tirzepatide: A Case Report e70173 EN Mihiro Sue Department of Diabetology and Metabolism, NHO Okayama Medical Center Mayu Watanabe Department of Diabetology and Metabolism, NHO Okayama Medical Center Ayumi Inoue Department of Diabetology and Metabolism, NHO Okayama Medical Center Akihiro Katayama Department of Diabetology and Metabolism, NHO Okayama Medical Center Sanae Teshigawara Department of Internal Medicine, Diabetes Center, Okayama Saiseikai General Hospital Yuichi Matsushita Department of Diabetology and Metabolism, NHO Okayama Medical Center Masaya Takeda Department of Diabetology and Metabolism, NHO Okayama Medical Center Izumi Iseda Department of Diabetology and Metabolism, NHO Okayama Medical Center Jun Eguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kazuyuki Hida Department of Diabetology and Metabolism, NHO Okayama Medical Center This report describes the first case of maturity-onset diabetes in young (MODY) with HNF1B mutation started administration of the dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, tirzepatide. A 26-year-old female with a 15-year history of diabetes mellitus was diagnosed with MODY, which is characterized by decreased insulin secretion. She was treated with tirzepatide, which significantly improved her glycemic management; insulin secretion increased the fasting serum C-peptide immunoreactivity from 0.36 to 1.09 ng/mL. The patient discontinued glimepiride, and her total daily insulin dose was reduced from 88 to 4 units. This report highlights the glucose-lowering effects of tirzepatide in a patient with MODY who has the HNF1B p.Glu105Lys mutation. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0897-3806 38 2 2025 Ethical Use of Cadaveric Images in Anatomical Textbooks, Atlases, and Journals: A Consensus Response From Authors and Editors 222 225 EN Joe Iwanaga Department of Neurosurgery, Tulane University School of Medicine Hee‐Jin Kim Division in Anatomy & Development Biology, Department of Oral Biology, Yonsei University College of Dentistry Keiichi Akita Department of Clinical Anatomy, Tokyo Medical and Dental University (TMDU) Bari M. Logan UK Ralph T. Hutchings UK Nicolás Ottone Department of Integral Adult Dentistry, Center for Research in Dental Sciences (CICO), Dental School, Universidad de La Frontera Yoichi Nonaka Department of Neurosurgery, Tokai University School of Medicine Mahindra Anand Department of Anatomy, Rama Medical College & Research Centre Danny Burns Department of Anatomical Sciences, School of Medicine, St. George's University Vishram Singh Department of Anatomy, Kasturba Medical College Mangalore, Manipal Academy of Higher Education Maria Peris‐Celda Department of Neurologic Surgery, Mayo Clinic Francisco Martinez‐Soriano Department of Anatomy, University of Valencia Nihal Apaydin Department of Anatomy, Faculty of Medicine, Ankara University Amgad Hanna Department of Neurological Surgery, University of Wisconsin Nobutaka Yoshioka Department of Neuroplastic and Reconstructive Surgery Social Medical Corporation Kotobukikai Tominaga Hospital Juan Fernandez‐Miranda Department of Neurosurgery, Stanford University School of Medicine Mi‐Sun Hur Department of Anatomy, Daegu Catholic University School of Medicine Mohammadali M. Shoja Department of Medical Education, Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University (NSU) Farhood Saremi Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Ronald Reagan UCLA Medical Center Francisco Reina Medical Sciences Department, Faculty of Medicine, Clinical Anatomy, Embryology and Neuroscience Research Group, University of Girona Yoko Tabira Division of Gross and Clinical Anatomy, Department of Anatomy, Kurume University School of Medicine Anna Carrera Medical Sciences Department, Faculty of Medicine, Clinical Anatomy, Embryology and Neuroscience Research Group, University of Girona Jonathan D. Spratt University Hospital of North Durham S. Yen Ho Cardiac Morphology, Royal Brompton & Harefield Hospitals Shumpei Mori University of California Los Angeles (UCLA) Cardiac Arrhythmia Center, Cardiovascular and Interventional Programs, UCLA Health System, David Geffen School of Medicine at UCLA Noritaka Komune Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University Koichi Watanabe Division of Gross and Clinical Anatomy, Department of Anatomy, Kurume University School of Medicine Alberto Prats‐Galino Laboratory of Surgical NeuroAnatomy (LSNA), director of the Body Donation and Dissection Rooms Service, Faculty of Medicine and Health of Science, University of Barcelona Jose De Andrés Surgery Specialties Department, University of Valencia Miguel Angel Reina CEU‐San‐Pablo University School of Medicine Peter H. Abrahams Warwick Medical School Robert H. Anderson Biosciences Institute, Newcastle University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Marios Loukas Department of Anatomical Sciences, School of Medicine, St. George's University R. Shane Tubbs Department of Neurosurgery, Tulane University School of Medicine Nowadays, consent to use donor bodies for medical education and research is obtained from the body donors and their families before the donation. Recently, the International Federation of Associations of Anatomists (IFAA) published guidelines that could restrict the appearance of cadaveric images in commercial anatomical resources such as textbooks and other educational products. These guidelines state that the donor must expressly consent to using such images for this purpose. Cadaveric photos and drawings made from dissections of cadavers have been used in anatomy textbooks and atlases for hundreds of years. They are invaluable for anatomy students and clinical/surgical practitioners. The IFAA guidelines should not restrict the use of those older books; to do so would infringe the rights of those seeking knowledge from these resources. As the images in such textbooks and atlases are anonymized and are used for teaching and research, and the donors and their families are informed about this before the donation, we believe no additional consent is needed. It is impossible to separate educational from “commercial” usage entirely in any situation, e.g., publications from publishers and the use of cadavers in medical schools. Therefore, our best efforts to avoid unethical use of cadaveric images by following traditional consent processes are still needed so that more people will reap the benefits from them. As senior textbook/atlas authors/editors from over 10 countries, we believe that using cadaveric images in anatomy textbooks is appropriate, and no additional consent should be necessary. Such usage falls within the good faith of professionals using these invaluable gifts. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2328-9503 2025 Dorsolateral Cervical Cord T2 Hyperintensity in KIF1C-Related Disease (Spastic Paraplegia 58): Two Long-Duration Cases EN Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo Masao Osaki Department of Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Miho Osako Department of Neurology, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled Chisen Takeuchi Department of Neurology, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Jun Mitsui Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Ryo Kurokawa Department of Radiology, Graduate School of Medicine, The University of Tokyo Harushi Mori Department of Radiology, School of Medicine, Jichi Medical University Yuji Takahashi Department of Neurology, Graduate School of Medicine, The University of Tokyo Jun Goto Department of Neurology, Graduate School of Medicine, The University of Tokyo Shoji Tsuji Institute of Medical Genomics, International University of Health and Welfare Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Pathogenic variants in KIF1C cause Spastic Paraplegia 58 (SPG58), typically presenting with cerebellar ataxia and spastic paraparesis. We report two unrelated patients with spastic paraparesis, cerebellar ataxia, and tremor. Whole-exome sequence analysis identified novel homozygous variants in the motor domain of KIF1C (NM_006612.6): c.921G>A (p.Trp307Ter) and c.607C>T (p.Arg203Trp). In addition to the canonical brain MRI showing leukoencephalopathy with posterior dominance and hyperintensity along the corticospinal tracts, both patients showed symmetric T2 hyperintensity confined to the lateral and dorsal columns of the cervical cord. Given the long disease durations (22 and 51 years), these findings may represent late-emerging or previously overlooked spinal cord involvement and broaden the neuroradiological spectrum of SPG58. 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.

Wiley Acta Medica Okayama 1085-9489 30 4 2025 A Case of Retinopathy–Sensory Neuropathy Syndrome With a Novel Compound Heterozygous FLVCR1 Variant e70082 EN Yumiko Nakano Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Fukui Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Deguchi Department of Neurology, Okayama City General Medical Center Chika Matsuoka Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohito Kawano Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Taira Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayaka Matsuo Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Osakada Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Taijun Yunoki Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Emi Nomura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mami Takemoto Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuta Morihara Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background and Aims: Retinopathy–sensory neuropathy syndrome (RETSNS), also known as posterior column ataxia with retinitis pigmentosa (PCARP), is a rare neurodegenerative disorder that is caused by biallelic pathogenic variants in FLVCR1. Here, we report a case of a Japanese patient with RETSNS. Methods: Clinical, neuroradiological, and electrophysiological findings were documented. Whole-genome sequencing was performed. Subcloning was carried out to confirm compound heterozygosity. A functional assay was performed to assess the pathogenicity of the variants. Results: The patient showed retinitis pigmentosa and sensory ataxia. Over the course of the disease, autonomic dysfunction has become increasingly evident. Despite consanguinity in the family, whole-genome sequencing identified two heterozygous variants in FLVCR1 (c.369T>G, p.Phe123Leu and c.733A>G, p.Asn245Asp). Cloning of the PCR product followed by Sanger sequencing indicated compound heterozygosity of the variants. Immunocytochemistry of HEK293FT cells transfected with plasmids containing wild-type or variant FLVCR1 cDNA demonstrated altered subcellular localization of the variant FLVCR1 proteins, characterized by reduced membrane localization. Interpretation: We report a novel variant in FLVCR1 causing RETSNS. The functional assay supports the pathogenicity of the variants. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 13 4 2025 Identification of New Repeat Expansion Diseases 244 249 EN Hiroyuki Ishiura Department of Neurology, Okayama UniversityGraduate School of Medicine, Dentistry and Pharmaceutical Sciences Through a genetic study of benign adult familial myoclonus epilepsy (BAFME) type 1, TTTCA and TTTTA repeat expansions have been identified in intron 4 of SAMD12. Lengths of expanded repeats inversely correlated with age at onset of epilepsy. Gain-of-toxic function mechanisms are suggested by the presence of UUUCA-repeat-containing RNA foci. From families with BAFME who did not have repeat expansions in SAMD12, we identified expanded TTTCA and TTTTA repeats in TNRC6A and RAPGEF2. These findings indicated a strong correlation between the repeat motif and the phenotype, leading to the identification of other types of BAFME. We then conducted genetic analysis of neuronal intranuclear inclusion disease (NIID), oculopharyngeal myopathy with leukoencephalopathy (OPML), and oculopharyngodistal myopathy (OPDM). From the observation that NIID, OPML, and OPDM, in addition to fragile X-associated tremor/ataxia syndrome, have shared clinical features, a direct search for CGG repeat expansions successfully led to the identification of the causative genes. Here, I review recent studies on repeat expansions. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 13 12 2025 Focal Nodular Hyperplasia of the Liver Mimicking Gastric Submucosal Tumor e71666 EN Yohei Masuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiaki Soejima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Focal nodular hyperplasia (FNH) is a common benign hepatic tumor, typically featuring a central scar with a spoke-wheel pattern on abdominal ultrasound. This case highlights a rare presentation of FNH causing extragastric compression that mimicked a gastric submucosal tumor on esophagogastroduodenoscopy. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2189-7948 26 4 2025 Video review by utilizing asynchronous video communication platform 375 378 EN Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eiko Mitsuda Kato & Namiki-dori Hospital Yukichika Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Kato Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mano Soshi BonBon, Inc Masaya Higuchi Harvard Medical School Mikako Obika Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadayuki Hashimoto Department of Emergency Medicine, Brigham and Women's Hospital Background: Video review is widely recognized as an effective method for teaching communication; however, it can increase educators' workload and learners' stress. Methods: We utilized Tsucom, an online platform developed by BonBon, Inc., which enables asynchronous video communication instead of traditional styles. An 11-min and 42-s consultation video from a fifth-year resident was uploaded, and 10 physicians provided 30 text-based feedback. Results: In this pilot survey, the utility and ease of use were rated 4.4 and 4.1 out of 5, respectively. Conclusions: While asynchronous online video reviews provided flexibility and greater participation, challenges remain, and further trials and evaluations were deemed necessary. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0960-7412 120 1 2024 OsHAK4 functions in retrieving sodium from the phloem at the reproductive stage of rice 76 90 EN Jing Che Institute of Plant Science and Resources, Okayama University Naoki Yamaji Institute of Plant Science and Resources, Okayama University Shao Fei Wang Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences Yue Xia Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences Shun Ying Yang Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences Yan Hua Su Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences Ren Fang Shen Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences Jian Feng Ma Institute of Plant Science and Resources, Okayama University Soil salinity significantly limits rice productivity, but it is poorly understood how excess sodium (Na+) is delivered to the grains at the reproductive stage. Here, we functionally characterized OsHAK4, a member of the clade IV HAK/KUP/KT transporter subfamily in rice. OsHAK4 was localized to the plasma membrane and exhibited influx transport activity for Na+, but not for K+. Analysis of organ- and growth stage-dependent expression patterns showed that very low expression levels of OsHAK4 were detected at the vegetative growth stage, but its high expression in uppermost node I, peduncle, and rachis was found at the reproductive stage. Immunostaining indicated OsHAK4 localization in the phloem region of node I, peduncle, and rachis. Knockout of OsHAK4 did not affect the growth and Na+ accumulation at the vegetative stage. However, at the reproductive stage, the hak4 mutants accumulated higher Na+ in the peduncle, rachis, husk, and brown rice compared to the wild-type rice. Element imaging revealed higher Na+ accumulation at the phloem region of the peduncle in the mutants. These results indicate that OsHAK4 plays a crucial role in retrieving Na+ from the phloem in the upper nodes, peduncle, and rachis, thereby preventing Na+ distribution to the grains at the reproductive stage of rice. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2691-1299 5 3 2025 Synthesis of Oligodeoxynucleotide Containing Pseudo‐Deoxycytidine and Its Triphosphate Derivative e70101 EN Ryo Miyahara Graduate School of Pharmaceutical Sciences, Kyushu University Yosuke Taniguchi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University This article describes a detailed synthetic protocol for the preparation of oligodeoxynucleotide (ODN) containing pseudo-deoxycytidine (ψdC) and its triphosphate derivative (ψdCTP). These molecules were synthesized as novel compounds that recognize iso-2'-deoxyguanosine (iso-dG) in DNA. Iso-dG is one of the tautomers of 2-hydroxy-2'-deoxyadenosine (2-OH-dA), which is known as an oxidatively damaged nucleobase, and its selective recognition in DNA is expected to play a very important role in the diagnosis and pathogenesis of diseases. The hydroxyl groups of the known glycal compound were protected with silyl groups, and then coupled with 5-iodouracil under Mizorogi-Heck reaction conditions, yielding ψdU after desilylation and diastereoselective reduction. The endocyclic amino group of ψdU was protected by the benzyl group. Subsequently, the carbonyl group at the 6-position of the nucleobase was activated and converted to an amino group through treatment with aqueous ammonia. The benzyl group was removed, and the exocyclic amino group was protected with a benzoyl group. On one hand, the silyl groups at the 3’ and 5’ positions were deprotected, converted into a phosphoramidite unit, and incorporated into an ODN. On the other hand, the hydroxyl group at the 5’ position was selectively deprotected and then directly converted into the triphosphate using Van Boom's reagent under acidic conditions. © 2025 The Author(s). Current Protocols published by Wiley Periodicals LLC. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0031-9317 177 4 2025 Comparative Transcriptome Reveals ART1-Dependent Regulatory Pathways for Fe Toxicity Response in Rice Roots e70398 EN Yoshiaki Ueda Crop, Livestock and Environment Division, Japan International Research Center for Agricultural Sciences Naoki Yamaji Institute of Plant Science and Resources, Okayama University Matthias Wissuwa Crop, Livestock and Environment Division, Japan International Research Center for Agricultural Sciences Iron (Fe) is an essential element for plants, but an excess supply can have detrimental effects. Fe toxicity induces complex physiological and genetic responses, and due to this complexity, the knowledge of transcriptional regulatory mechanisms under Fe toxicity is very limited. Previous studies suggested that plant responses to excess Fe involve oxidative stress caused by reactive oxygen species (ROS), which itself causes transcriptional changes. We hypothesized that dissecting these complex responses could lead to the identification of a novel factor and conducted a comparative transcriptome analysis using roots of rice plants exposed to nutrient solutions containing 1 or 5 mM of hydrogen peroxide (a major form of ROS) or 300 mg L−1 of Fe (as FeSO4). Genes induced by hydrogen peroxide overlapped with 62%, 49%, and 30% of Fe toxicity-upregulated genes at 3 h, 1 day, and 3 days following treatment initiation. Subsequent gene co-expression analyses classified genes into 21 groups with varying responsiveness to ROS and Fe toxicity. Genes in group 15 were specifically upregulated by Fe toxicity and overlapped significantly with aluminum (Al)-inducible genes and target genes of the Zn-finger transcription factor, ART1, which regulates Al response in rice roots. Additional experiments using the art1 knock-out mutant demonstrated that ART1 is crucial for upregulating genes such as STAR2 and FRDL4 in response to Fe toxicity. This study reveals the contribution of ART1-dependent regulatory pathways in rice roots under Fe toxicity. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0361-5995 89 3 2025 Autoclaved lightweight aerated concrete suppressed N2O and CO2 emissions from paddy soil e70091 EN Nagoda R. R. W. S. Rathnayake Department of Soil Science, Faculty of Agriculture, University of Ruhuna Morihiro Maeda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Dewpura A. L. Leelamanie Department of Soil Science, Faculty of Agriculture, University of Ruhuna Atsushi Yatagai Clion Co. Ltd Autoclaved lightweight aerated concrete (AAC), a construction waste that is utilized as a soil amendment, can influence terrestrial carbon dioxide (CO2) emissions. Still, no evidence exists regarding its impact on the emission of nitrous oxide (N2O), which has a higher global warming potential. This study examined effects of AAC on CO2 and N2O emissions from paddy soil under compacted and non-compacted conditions, under 60% and 100% water-holding capacity (WHC). Samples were incubated in glass vials (25°C) for 21 days. Emissions of CO2 and N2O were measured on days 0, 1, 3, 7, 14, and 21 using gas chromatography. The results revealed that AAC significantly (p < 0.05) lowered N2O emission rate during the whole period of incubation, while it suppressed CO2 emission rate only at the early stages (∼7 days) of incubation. In compacted soil, the emissions of CO2 were significantly lower, while N2O was significantly higher than that in non-compacted soil, showing the influence of soil physical conditions. The emissions of CO2 and N2O were significantly lower at 100% WHC than those at 60% WHC. AAC suppressed both CO2 and N2O emissions under both compaction and WHC levels. The results confirm that AAC supports suppressing terrestrial emission of both CO2 and N2O, indicating that AAC has a potential as a sustainable soil amendment that enhances the climate change resilience. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1748-3735 21 1 2025 Japanese Adult Day Service Nurses' Bathing Decisions for Persons Requiring Long‐Term Care: A Focused Ethnography e70052 EN Kanako Miyoshi Graduate School of Health Sciences, Okayama University Keiko Mori Graduate School of Health Sciences, Okayama University Introduction: Adult day services in Japan operate under the Long-Term Care Insurance Law, and care is provided mainly by caregivers. However, because doctors are often not on site, nurses manage the health of the person requiring long-term care. Adult day services provide bathing and functional training; however, although Japanese-style bathing relieves fatigue and brings a sense of well-being, it also entails the risk of bathing accidents for those in need of care. To continue living at home, those in need of care who have difficulty bathing at home must be provided with safe bathing during adult day services and supported in returning home safely. Nurses are responsible for accurately assessing the health status of users and implementing safe bathing. This study aimed to identify how nurses working in adult day services make bathing decisions for home-dwelling persons requiring long-term care. Method: Qualitative manifest and latent content analyses were performed using a focused ethnography. Findings: Six themes were identified: ‘gather information to compare with baseline’, ‘make observations based on information from others to understand the big picture’, ‘give persons time to get in shape’, ‘consideration of life at home’, ‘determining the need for medical institutions’ and ‘devise ways to communicate to promote collaboration’. Conclusions: Adult day service nurses' decisions about whether to bathe persons requiring care are characterised by their emphasis on information from others, consideration of the home living conditions of persons requiring care and their wishes regarding bathing. In addition, based on their observations, they determine the need for cooperation with medical institutions and communicate this information to family members and multiple professions. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1433-7851 64 13 2025 Conduction Band and Defect Engineering for the Prominent Visible‐Light Responsive Photocatalysts e202419624 EN Akira Yamakata Graduate School of Natural Science and Technology, Okayama University Kosaku Kato Graduate School of Natural Science and Technology, Okayama University Takafumi Ogawa Nanostructures Research Laboratory, Japan Fine Ceramics Center Kanta Ogawa Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Makoto Ogawa Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Daichi Kato Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Chengchao Zhong Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Akihide Kuwabara Nanostructures Research Laboratory, Japan Fine Ceramics Center Ryu Abe Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Hiroshi Kageyama Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Controlling trap depth is crucial to improve photocatalytic activity, but designing such crystal structures has been challenging. In this study, we discovered that in 2D materials like BiOCl and Bi4NbO8Cl, composed of interleaved [Bi2O2]2+ and Cl- slabs, the trap depth can be controlled by manipulating the slab stacking structure. In BiOCl, oxygen vacancies (VO) create deep electron traps, while chlorine vacancies (VCl) produce shallow traps. The depth is determined by the coordination around anion vacancies: VO forms strong σ bonds with Bi-6p dangling bonds below the conduction band minimum (CBM), while those around Cl are parallel, forming weak π-bonding. The strong re-hybridization makes the trap depth deeper. In Bi4NbO8Cl, VCl also creates shallow traps, but VO does not produce deep traps although Bi-6p orbitals are also forming strong σ bonding. This difference is attributed to the difference of the energy level of CBM. In both cases, the CBM consists of Bi-6p orbitals extending into the Cl layers. However, these orbitals are isolated in BiOCl, but those in Bi4NbO8Cl are bonded with each other between neighboring [Bi2O2]2+ layers. This unique bonding-based CBM prevents the formation of deep electron traps, and significantly enhances H2 evolution activity by prolonging the lifetime of highly reactive free electrons. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2211-5463 15 10 2025 Osmotic pressure‐induced calcium response states 1714 1722 EN Zidan Gao Department of Cardiovascular Physiology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiji Naruse Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Okayama Japan Masatoshi Morimatsu Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Okayama Japan Osmotic pressure is essential for maintaining cellular homeostasis; however, the mechanisms by which cells sense and respond to acute osmotic stress remain incompletely understood. Here, we applied rapid osmotic pressure stimulation to cultured HEK293T cells and observed dynamic intracellular calcium responses. Acute hypotonic stimulation evoked calcium response patterns, whereas hypertonic and isotonic stress did not elicit similar effects. Mechanistically, these calcium signals originated from the endoplasmic reticulum via ryanodine receptor 2 and propagated to neighboring cells through Connexin 43-mediated gap junctions. These findings reveal a previously unrecognized role for calcium signaling in the acute cellular response to osmotic stress, providing new insights into the mechanisms of intercellular communication during osmotic adaptation. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2692-4609 6 1 2025 Japanese Multi‐Institution Study of Success Rates of Wire‐Guided Biliary Cannulation During Endoscopic Retrograde Cholangiopancreatography in Relation to Guidewire tip Length (JMIT Study) (With Video) e70144 EN Takeshi Ogura Endoscopy Center, Osaka Medical and Pharmaceutical University Yuki Tanisaka Gastroenterology, Saitama Medical University International Medical Center Masanari Sekine Department of Gastroenterology Jichi Medical University, Saitama Medical Center Katsumasa Kobayashi Department of Gastroenterology, Tokyo Metropolitan Bokutoh Hospital Hirotsugu Maruyama Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University Shinji Hirai Department of Medicine, Division of Gastroenterology, Kurume University School of Medicine Hideyuki Shiomi Department of Gastroenterology, Division of Hepatobiliary and Pancreatic Diseases, Hyogo Medical University Minoru Shigekawa Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine Masaki Kuwatani Department of Gastroenterology and Hepatology, Hokkaido University Hospital Kenji Ikezawa Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute Masahiro Itonaga Second Department of Internal Medicine, Wakayama Medical University Mamoru Takenaka Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University Susumu Hijioka Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital Tsukasa Ikeura Third Department of Internal Medicine, Kansai Medical University Shinpei Doi Department of Gastroenterology, Teikyo University Mizonokuchi Hospital Nao Fujimori Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University Kazuya Koizumi Department of Gastroenterology, Medicine Center, Shonan Kamakura General Hospital Yousuke Nakai Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo Tadahisa Inoue Department of Gastroenterology, Aichi Medical University Shuntaro Mukai Department of Gastroenterology and Hepatology, Tokyo Medical University Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Ryuki Minami Department of Gastroenterology, Tenri Hospital Koichiro Mandai Department of Gastroenterology, Kyoto Second Red Cross Hospital Atsuhiro Matsuda Department of Internal Medicine, Toyama Prefectural Central Hospital Takuji Iwashita First Department of Internal Medicine, Gifu University Hospital Hiroki Kawashima Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine Takao Itoi Department of Gastroenterology and Hepatology, Tokyo Medical University Objective: Wire-guided cannulation (WGC) reportedly increases the successful biliary cannulation rate and reduces the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis. Currently, various types of guidewires are available. However, the effect of the length of flexible-tip guidewires on the success rate of biliary cannulation under WGC and the rate of adverse events, especially post-endoscopic retrograde cholangiopancreatography pancreatitis, is unclear. The aim of this study was to compare the influence of long-tapered and short-tapered tips of a 0.025-inch guidewire on outcomes in primary selective biliary cannulation. Methods: Consecutive patients who underwent biliary access under endoscopic retrograde cholangiopancreatography guidance using WGC at 27 high-volume centers in Japan were enrolled in this prospective registration study. The primary outcome was the technical success rate of biliary cannulation. The secondary outcomes were the rates of adverse events, biliary cannulation time, and number of guidewire insertions into the pancreatic duct. Results: A total of 530 patients underwent biliary cannulation for biliary disease with native papilla between April 2021 and December 2023. The technical success rate of biliary cannulation was 86.1% (161/187) in the long-tip group and 84.3% (289/343) in the short-tip group, indicating no significant differences between the two groups. Although the frequency of post-endoscopic retrograde cholangiopancreatography was not significantly different, the successful biliary cannulation rate without guidewire mis-insertion into the main pancreatic duct was significantly higher in the long tip group (64.7%, 121/187) compared with the short tip group (54.2%, 186/343p = 0.02). Conclusions: In conclusion, WGC using long-tip guidewires might reduce the risk of guidewire insertion into the main pancreatic duct. 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. Method: This retrospective, multicenter study included consecutive patients with liver abscesses between January 2019 and November 2024. The primary outcome in this study was the clinical success rate compared between EUS-LAD and PTAD. Results: During the study period, 1012 consecutive patients developed liver abscesses. Of them, 734 patients were excluded, 43 underwent EUS-LAD and 235 patients underwent PTAD. After propensity score-matched analysis, the clinical success rate was significantly higher in the EUS-LAD group (97.7%, 42/43) than in the PTAD group (79.1%, 34/43) (p = 0.007). After a propensity score-matched analysis, 25 patients were included in each group. The clinical success rate was significantly higher in the EUS-LAD group (100%, 25/25) than in the PTAD group (84%, 21/25) (p = 0.037). Adverse events were also significantly higher in the PTAD group (16%, 5/25) than in the EUS-LAD group (p = 0.025). In addition, the median length of hospital stay was significantly shorter in the EUS-LAD group (15 days) than in the PTAD group (22 days) (p = 0.005). Conclusions: EUS-LAD using a metal stent might be one of the options, but further randomized, controlled trials are needed. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1341-8076 51 11 2025 The Short‐Term Impacts of Japan's 2024 Physician Working‐Hour Limits on Labor Conditions, Self‐Directed Professional Development, and Happiness Among Obstetrician‐Gynecologists e70112 EN Yuto Maeda Department of Public Health, Institute of Science Tokyo Satoru Nakagawa Department of Obstetrics and Gynecology, Osaka University Kentaro Nakanishi Department of Obstetrics and Gynecology, Asahikawa Medical University Eri Inoue Aiiku Maternal and Child Health Center, Aiiku Hospital Daisuke Inoue Department of Obstetrics and Gynecology, University of Fukui Saki Kido Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University Michiko Kido Department of Obstetrics and Gynecology, Japanese Red Cross Medical Center Kaori Koga Department of Obstetrics and Gynecology, Reproductive Medicine Chiba University Shunji Suzuki Department of Obstetrics and Gynecology, Nippon Medical School Yukio Suzuki Department of Gynecology, Kanagawa Cancer Center Junko Haraga Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eiko Yamamoto Department of Healthcare Administration, Nagoya University Graduate School of Medicine Takeshi Umazume Department of Obstetrics and Gynecology, Hokkaido University Yoshihito Yokoyama Department of Obstetrics and Gynecology, Hirosaki University Graduate School of Medicine Akira Iwase Department of Obstetrics and Gynecology, Gunma University Graduate School of Medicine Tomoaki Ikeda Saiseikai Matsusaka General Hospital Yoshio Yoshida Department of Obstetrics and Gynecology, University of Fukui Yoshiki Kudo Department of Obstetrics and Gynecology, Hiroshima University Takashi Sugiyama Department of Obstetrics and Gynecology, Ehime University Graduate School of Medicine Kiyonori Miura Department of Obstetrics and Gynecology, Nagasaki University Hideaki Yahata Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University Nobuya Unno Center for Perinatal Medicine, JCHO Sagamino Hospital Kentaro Kurasawa Department of Obstetrics and Gynecology, Yokohama City University Graduate School of Medicine Takahide Maenaka Department of Obstetrics and Gynecology, Higashiosaka City Medical Center Etsuko Miyagi Department of Obstetrics and Gynecology, Yokohama City University Graduate School of Medicine Kiyoko Kato Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University Yasuhito Kato Department of Obstetrics and Gynecology, Asahikawa Medical University Objective: To examine the short-term impacts of Japan's newly implemented physician working-hour limits (April 2024) on working conditions, self-directed professional development (SDPD), defined as activities undertaken outside working hours to enhance one's professional skills, and work-related happiness among obstetrician-gynecologists (OB-GYNs). Methods: An online survey was conducted between July 8 and July 31, 2024, targeting 867 Japan Society of Obstetrics and Gynecology members. Five hundred and fourteen full-time practitioners who had not changed workplaces around April 2024 and had no missing data were analyzed. Participants were stratified by regulation levels (A, B, C, discretionary labor system, those who don't know their own level), and their working hours, anticipated income, SDPD satisfaction, and happiness (0–10 scale) were assessed. We used multivariate linear regression to evaluate the influence of labor condition changes on happiness and explored interactions involving unpaid overtime, income changes, and SDPD satisfaction. Results: Compared with level A (up to 960 h of overtime per year), participants at levels B and C (up to 1860 h of overtime per year) reported significantly lower happiness (p < 0.001). Most respondents observed no major shifts in working conditions since March 2024, yet about 40% did not record SDPD hours that meet the working hour requirement as official work time. Adjusted analyses revealed that decreased income and unsatisfactory SDPD significantly lowered happiness, whereas higher SDPD satisfaction increased it (β: −0.64 [−1.07, −0.21], −0.98 [−1.46, −0.50], and 0.90 [0.44, 1.35], respectively). Subgroup analysis indicated that rising unpaid overtime further reduced happiness among those dissatisfied with SDPD (−1.43 [−2.41, −0.45]). Conclusions: The new working-hour limits had minimal impact on labor conditions in the short run. However, satisfaction with SDPD was positively associated with happiness, whereas anticipated decreases in income were correlated with lower happiness. 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.

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.

Wiley Acta Medica Okayama 0305-182X 2025 Is Pain Intensity Related to Psychosocial Factors in Chronic Non‐Nociceptive Orofacial Pain Patients? EN Akiko Kawase Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitoshi Higuchi Department of Dental Anesthesiology, Okayama University Hospital Fumika Hashimoto Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Saki Miyake Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukiko Nishioka Department of Dental Anesthesiology, Okayama University Hospital Midori Inoue Department of Dental Anesthesiology, Okayama University Hospital Hitomi Ujita Department of Dental Anesthesiology, Okayama University Hospital Aki Kawauchi Department of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Shigeru Maeda Department of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Takuya Miyawaki Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: In order to understand the psychological aspects of chronic pain, it is important to consider the relationships between pain and psychosocial factors in patients with chronic pain. While psychosocial factors are known to affect pain intensity in temporomandibular disorders, few studies have evaluated them in patients with other types of chronic orofacial pain. Objective: The purpose of the present study was to evaluate the relationships between pain intensity and patient characteristics, diagnostic categories and psychosocial factors in chronic non-nociceptive orofacial pain patients. Methods: In a retrospective, cross-sectional study, we collected information from the medical records of 123 patients with chronic non-nociceptive orofacial pain. Pain intensity was measured using the Brief Pain Inventory (BPI) total score. Analysis of the correlations among the variables revealed several strong correlations. Principal component analysis identified two components: the psychological distress and self-efficacy/quality of life (QOL) components. Multiple linear regression analyses of the overall study population and each ICOP pain category were also performed. Results: In the overall sample, higher BPI scores were significantly associated with a greater psychological distress component and lower self-efficacy/QOL component. The pain category was not a significant predictor of the BPI score. In the subgroup analyses, both components were significant predictors of the BPI score in myofascial orofacial pain; whereas, only the self-efficacy/QOL component was in idiopathic orofacial pain. Conclusion: The results indicated that pain intensity in chronic non-nociceptive orofacial pain is related to the self-efficacy/QOL psychosocial factor component. These findings suggest that assessing psychosocial factors may be clinically important for the diagnosis and treatment of chronic orofacial pain. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0041-1132 65 9 2025 Novel method for autologous peripheral blood stem cell harvest using highly concentrated sodium citrate solution replacing acid citrate dextrose solution A 1662 1672 EN Wataru Kitamura Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Department of Hematology and Oncology, Okayama University Hospital Masaya Abe Department of Hematology and Oncology, Okayama University Hospital Kazuhiro Ikeuchi Department of Hematology and Oncology, Okayama University Hospital Joji Shimono Department of Hematology and Oncology, Okayama University Hospital Kana Washio Department of Pediatrics, Okayama University Hospital Fumio Otsuka Division of Clinical Laboratory, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Background: As the processed blood volume increases, a larger amount of anticoagulant (AC) is required, which leads to a serious issue of fluid dilution in large-volume leukocytapheresis (defined as ≥3-fold total blood volume). We previously reported a novel method for allogeneic peripheral blood stem cell harvest (PBSCH) using highly concentrated sodium citrate (HSC; 5.32%), which shortened the procedure time and reduced the need for an AC solution without heparin. In this study, we extended this novel method to autologous PBSCH (auto-PBSCH) and compared it with patients who received auto-PBSCH using normal concentrated sodium citrate (NSC; 2.2%). Study Design and Methods: We retrospectively analyzed consecutive auto-PBSCH data obtained using the Spectra Optia continuous mononuclear cell collection mode between May 2017 and May 2025 at our institution. Results: Leukocytapheresis was performed using NSC in 36 patients and HSC in 22. In the HSC group, patients tended to be younger, had significantly lower body weight, and had significantly fewer hematopoietic tumors as primary diseases compared to the NSC group. After propensity score-matched cohort adjusted for patient background, the total amount of AC solution was significantly lower (694 [range, 77–1648] vs. 298 mL [range, 64–797], p = .02), and procedure time was significantly shorter (224 [range, 117–395] vs. 181 min [range, 103–309], p = .048) in the HSC group. Furthermore, the loss rates of magnesium and potassium were lower in the HSC group. Conclusion: This novel leukocytapheresis method demonstrated the efficacy and safety in auto-PBSCH, while minimizing the patient burden. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Factors influencing pain management practices among nurses in university hospitals in Western Japan: A cross-sectional study using hierarchical multiple regression analysis EN Mengyao XI Graduate School of Health Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Trends in childhood obesity in Japan: A nationwide observational study from 2012 to 2021 EN Shintaro FUJIWARA 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 Impact of Birth Order on Paediatric Allergic Diseases: A National Birth Cohort in Japan EN Mitsuro KOBAYASHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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. Methods: We searched Cochrane, MEDLINE, and EMBASE for English language, pharmaceutical, and/or behavioral intervention studies in adults with obesity where the explicit aim of the study was weight reduction defined as a percent of body weight. Reviewers screened citations and extracted data including study characteristics. Results: From 16,164 abstracts, we included 30 citations which were mostly randomized controlled trials (RCTs) (n = 17) or quasi-experimental studies (n = 12) published between 1992 and 2024. Most of the studies had target weight loss goals between 3% and 10% of body weight (n = 28), while n = 2 had body weight loss goals of 15% or 30%. The proportion of participants who met the percent weight loss target ranged from 5.9% (nutrition only study) to 85% (pharmaceutical study). The studies reported different reasons for targeting a percentage of weight loss such as disease-specific outcomes, reduced risk of disease, or patient-reported outcomes. Conclusion: Percent weight loss targets were based on similar research and were often not feasible nor sustainable for most participants. The design of these interventions and evaluation of obesity management would benefit from more patient-focused parameters which could help to co-design comprehensive targets for research and practice. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1320-5358 30 5 2025 A Case of IgA Nephropathy With Membranoproliferative Glomerulonephritis-Like Features Miyu Kanazawa, e70057 EN Miyu Kanazawa Okayama University Medical School Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoya Aoki Okayama University Medical School Mihiro Sue Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Miyake Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naruhiko Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Department of Chronic Kidney Disease and Cardiovascular Disease, 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 A 73-year-old man was referred due to the onset of nephrotic-range proteinuria. He had been diagnosed with rheumatoid arthritis 18 years prior and had achieved remission with treatment, including methotrexate and janus kinase (JAK) inhibitor. Although routine follow-ups had not revealed any urinary abnormalities, subsequent tests detected proteinuria and hematuria in the absence of infection or other symptoms. As the urinary abnormalities persisted, with a serum albumin decrease and proteinuria measuring 5.7 g/day, indicating nephrotic syndrome, the patient was referred to our hospital for further evaluation, and a renal biopsy was performed. Light microscopy revealed mesangial cell proliferation, endocapillary proliferation and double-contoured basement membranes. Immunofluorescence microscopy showed IgA-dominant deposits in both mesangial areas and glomerular capillary walls. Transmission electron microscopy demonstrated electron-dense deposits in the mesangium and subendothelial regions, leading to the diagnosis of membranoproliferative glomerulonephritis (MPGN)-type IgA nephropathy. Immunostaining with the Gd-IgA1 (galactose-deficient IgA1)-specific antibody (KM55) was positive, consistent with the diagnosis. Following the initiation of steroid therapy, proteinuria rapidly decreased, achieving complete remission within 5 months. IgA nephropathy with MPGN-like features often presents as nephrotic syndrome, differing from the typical pathological and clinical presentation of IgA nephropathy, making differentiation from secondary MPGN and other diseases sometimes challenging. This case suggests that KM55 staining may offer additional information in differentiating atypical IgA nephropathy with non-classical pathological features. 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). Materials and Methods: Individuals with obesity disease diagnosed according to the criteria of the Japan Society for the Study of Obesity were registered in J-ORBIT from seven medical centers in Japan. We analyzed the relationship between body mass index (BMI), clinical characteristics, and the prevalence of obesity-related health disorders in this cohort. Results: Data were obtained from 1,169 individuals, with a mean (±SD) age of 56.9 ± 15.3 years and a BMI of 31.4 ± 6.1 kg/m2. The prevalence of health disorders varied substantially across BMI categories, with a higher BMI being associated with an increased prevalence of hyperuricemia or gout, obstructive sleep apnea syndrome or obesity hypoventilation syndrome, musculoskeletal disorders, and obesity-related kidney disease, as well as with a higher frequency of both a family history of obesity and of a history of childhood obesity. Among individuals with a BMI of ≥25 kg/m2, the prevalence of hypertension and dyslipidemia did not increase with BMI, whereas that of glucose intolerance decreased with increasing BMI. Conclusions: The J-ORBIT system, which collects clinical data in real time directly from EMRs, has the potential to provide insight into obesity and its associated health conditions, thereby contributing to improved care of affected individuals. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1328-8067 67 1 2025 Pediatric stroke risk and neurotrauma from roller coasters in amusement parks e70221 EN Tomoki Morikawa Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohei Tokioka Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Although rare, neurotrauma has been documented as a potential risk of high-speed, high-acceleration amusement park rides such as roller coasters. These attractions generate rapid acceleration, deceleration, sharp turns, and significant gravitational forces, which may stress the central nervous system and cerebrovascular structures. This review analyzed pediatric stroke cases (children 15 years old or younger) linked to roller-coaster rides reported in PubMed and summarized the key mechanisms and clinical features associated with such neurotrauma. Documented complications include internal and vertebral carotid artery dissections, with or without stroke, subdural hemorrhage, intraparenchymal hemorrhage, and post-traumatic migraines. The aim of this review is to alert healthcare providers to the possibility of stroke induced by roller-coaster rides, emphasizing the importance of timely diagnosis and management to prevent adverse outcomes. Key considerations include the recognition of risk factors, public education on potential risks, and strategies for preventing complications in at-risk populations. Although intracranial hemorrhage from roller-coaster rides is rare, individuals with predisposing conditions, such as prior head trauma or vascular abnormalities, should be evaluated carefully when presenting with neurological symptoms after such activities. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1085-3278 2025 Enhancing Soil Aggregation and Water Retention by Applying Kaolinite Clay to Post‐Tin‐Mined Land on Belitung Island, Indonesia EN Hirmas F. Putra Graduate School of Environmental and Life Science, Okayama University Yasushi Mori Graduate School of Environmental and Life Science, Okayama University Post-mining sandy soils have low water retention, which causes soil particle separation and persistent soil erosion. Although organic matter is commonly used for soil restoration, it is lightweight, washes away during heavy rain, and decomposes under strong sunlight. The high potential for extreme rainfall events in tropical regions poses significant challenges to restoration projects. Therefore, we investigated the impact of kaolinite clay particles on enhancing soil stability in post-mining sandy soils. Soil samples were collected from three sites representing different succession stages of post-mined land (0, 1, and 6 years since mining cessation) and an adjacent natural forest as the reference site on Belitung Island, Indonesia. Soil samples were treated with 1% or 5% kaolinite or left untreated (control) and incubated at 34°C to mimic the local conditions of the study area. The samples were then analyzed to determine the soil aggregate distribution, water holding capacity, and soil erodibility, and SEM imaging was performed to examine the soil particle morphology. The results revealed an increasing trend in the silt-sized aggregate content and a 2%–5% increase in water retention in the 6-year soils relative to the untreated soils. The highest water retention was observed in the 6-year post-mining soil sample. Kaolinite amendment significantly reduced soil erodibility by 40%–50% compared to the untreated soils, even in the early restoration period (0–1 year post-mining). Kaolinite improved soil aggregation and water retention in post-mining sandy soils while reducing soil erodibility—highlighting its potential for accelerating land restoration in mining-affected areas. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1552-4825 2025 Giant Choledochal Cyst in a Child With Spinocerebellar Ataxia: A Potential Molecular Link Through Aberrant Cytosolic Calcium Signaling e64296 EN Hiromi Sumitomo Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Akiyama Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Kaname Department of Genome Medicine, National Center for Child Health and Development Toshiki Takenouchi Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2470-9239 10 3 2025 Decreased homovanillic acid and 5‐hydroxyindoleacetic acid levels in the cerebrospinal fluid of patients with Dravet syndrome with parkinsonism 965 970 EN Ryo Sugiyama Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry Takashi Saito Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry Atsuko Katsumoto Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry Shota Yoneno Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry Tomoyuki Akiyama Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Hirofumi Komaki Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry Dravet syndrome (DS) is an early onset, developmental, and epileptic encephalopathy characterized by drug-resistant seizures and multiple comorbidities. It has been reported that in adulthood, it may be accompanied by parkinsonism, but the pathogenesis of this condition remains unclear. We performed dopamine transporter single-photon emission computed tomography (DAT SPECT) and measured monoamine metabolite levels in the cerebrospinal fluid (CSF) in two adult patients with DS who developed parkinsonism around the age of 30 years. DAT SPECT showed no abnormalities in either patient, whereas CSF tests revealed significant decreases in the levels of homovanillic and 5-hydroxyindoleacetic acids. One patient with severe symptoms was treated with levodopa–carbidopa, which improved parkinsonism manifestations. The other patient initiated treatment with a low dose and has been continuing the treatment without any reported side effects. In conclusion, CSF testing can detect a decrease in dopamine synthesis and may be useful in monitoring the efficacy of levodopa treatment in patients with DS and parkinsonism. Plain Language Summary: Dravet syndrome (DS) is an early onset, developmental, and epileptic encephalopathy. DS can lead to the development of parkinsonism in adulthood, a clinical syndrome characterized by tremor, slowed movements, and rigidity. Although parkinsonism is a significant issue for patients, its underlying pathology has not yet been elucidated. In this study, we confirmed that the levels of monoamine metabolites in the CSF were low in two patients, potentially shedding light on the pathology involved. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0007-1048 2025 Impact of methotrexate-dosing regimens for GVHD prophylaxis on clinical outcomes of HLA-matched allogeneic HSCT EN Tomotaka Suzuki Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences Tomoyasu Jo Department of Hematology, Graduate School of Medicine, Kyoto University Kota Yoshifuji Department of Hematology, Institute of Science Tokyo Tadakazu Kondo Department of Hematology, Graduate School of Medicine, Kyoto University Noriko Doki Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Centre, Komagome Hospital Yoshinobu Kanda Division of Hematology, Jichi Medical University Saitama Medical Centre Tetsuya Nishida Department of Hematology, Japanese Red Cross Aichi Medical Centre Nagoya Daiichi Hospital Yasushi Onishi Department of Hematology, Tohoku University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Takahiro Fukuda Department of Haematopoietic Stem Cell Transplantation, National Cancer Centre Hospital Masashi Sawa Department of Hematology and Oncology, Anjo Kosei Hospital Yuta Hasegawa Department of Hematology, Hokkaido University Hospital Kentaro Serizawa Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Shuichi Ota Department of Hematology, Sapporo Hokuyu Hospital Masatsugu Tanaka Department of Hematology, Kanagawa Cancer Centre Makoto Yoshimitsu Department of Hematology and Rheumatology, Graduate School of Medical and Dental Sciences, Kagoshima University Yoshiko Atsuta Japanese Data Centre for Haematopoietic Cell Transplantation Junya Kanda Department of Hematology, Graduate School of Medicine, Kyoto University Severe graft-versus-host disease (GVHD) remains a major complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT), necessitating optimal immunosuppressive strategies. This retrospective study used data from the Japanese Transplant Registry Unified Management Program to compare three methotrexate (MTX)-dosing regimens for GVHD prophylaxis in patients undergoing human leucocyte antigen (HLA)-matched allo-HSCT: a low-dose 3-day regimen (Ld3:10 mg/m2 on day 1, 7 mg/m2 on days 3 and 6), a low-dose 4-day regimen (Ld4: Ld3 with an additional 7 mg/m2 on day 11) and an original-dose 3-day regimen (Od3: 15 mg/m2 on day 1, 10 mg/m2 on days 3 and 6). Among 2537 analysed patients, Ld3 was the most commonly used regimen. Multivariate analyses showed no significant differences in the cumulative incidence of grade II–IV acute GVHD among regimens. However, Od3 was associated with an increased risk of grade III–IV acute GVHD, and Ld4 was linked to delayed neutrophil engraftment. This study is the first large-scale retrospective analysis of the impact of different MTX-dosing regimens on the outcomes of HLA-matched allo-HSCT, providing valuable insights into optimal MTX-dosing strategies in clinical practice. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2688-6146 6 5 2025 Late‐Onset Invasive Aspergillosis With Pituitary Involvement and Dysfunction Following CD19 Chimeric Antigen Receptor T‐Cell Therapy e70138 EN Daisuke Ikeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Nawada The Center for Graduate Medical Education, Okayama University Hospital Takumi Kondo Department of Hematology and Oncology, Okayama University Hospital Takayuki Shinohara Department of Fungal Infection, National Institute of Infectious Diseases Tomohiro Nagano Department of Hematology and Oncology, Okayama University Hospital Saya Kubota Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuichiro Hiyama Department of Hematology and Oncology, Okayama University Hospital Masaya Ueno Department of Hematology and Oncology, Okayama University Hospital Hiroki Kobayashi Department of Hematology and Oncology, Okayama University Hospital Keisuke Seike Department of Hematology and Oncology, Okayama University Hospital Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Daisuke Ennishi Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Masanori Makita Department of Hematology, Chugoku Central Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Introduction: Invasive fungal infection (IFI) after chimeric antigen receptor (CAR) T-cell therapy is less common than bacterial and viral infections, but can be fatal once it develops. As most cases occur within 30 days after CAR T-cell infusion, late-onset IFI—particularly mould infection—appears to be under-recognised. Discussion: We report an illustrative case of pituitary aspergillosis developing as late as one year after CD19 CAR T-cell therapy, highlighting a persistent risk in certain patients with delayed immune reconstitution. Conclusion: This case underscores the need for continued vigilance and individualised antifungal strategies to prevent IFI beyond the early post-infusion period. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission. 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.

Wiley Acta Medica Okayama 1464-6722 26 11 2025 Comparative Genomic Analysis Identifies FleQ and GcbB as Virulence-Associated Factors in Pseudomonas syringae pv. tabaci Strains e70168 EN Muhammad Taufiq Hidayat Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kei Yoshioka Faculty of Agriculture, Okayama University Takafumi Nishimura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Shuta Asai Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sachiko Masuda Center for Sustainable Resource Science, RIKEN-TRIP Ken Shirasu Center for Sustainable Resource Science, RIKEN-TRIP Nanami Sakata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mikihiro Yamamoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiteru Noutoshi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuhiro Toyoda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuki Ichinose Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hidenori Matsui Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Pseudomonas syringae pv. tabaci (Pta) is an important plant pathogen, which causes wildfire disease in Nicotiana species. However, the genetic basis underlying strain-level differences in virulence remains largely unresolved. To address this, we performed a comparative genomic analysis between a highly virulent strain Pta6605 and a less virulent strain Pta7375. Despite high overall genome similarity, we identified key single-nucleotide polymorphisms, including premature stop-codon mutations in seven open reading frames in Pta7375. Notably, point mutations in two regulatory genes, such as fleQ, which encodes a transcription factor essential for flagellar biogenesis and biofilm formation, and gcbB, which encodes a GGDEF domain-containing diguanylate cyclase responsible for cyclic dimeric guanosine monophosphate (c-di-GMP) synthesis, were implicated in virulence disparity. Functional analyses using deletion and locus replacement mutants in the Pta6605 background revealed that the disruption of fleQ markedly reduced motility, flagellin production, c-di-GMP accumulation, biofilm formation and virulence level mirroring the Pta7375 phenotype. The gcbB replacement mutant showed reduced disease symptom development, although c-di-GMP levels remained comparable to the Pta6605 wild type. Locus replacement between strains confirmed that a point mutation in fleQ was the primary driver of reduced motility and flagellin expression in Pta7375. These findings indicate that the reduced virulence of Pta7375 is associated with impaired regulation of flagella-related genes and disruption of the FleQ-mediated c-di-GMP signalling, underscoring the value of comparative genomics in disentangling the complex regulatory networks that govern virulence in plant pathogens. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1354-523X 2025 The Role of the Mylohyoid Line in the Spread of Mandibular Odontogenic Deep Neck Infection EN Eiji Iwata Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kyoichi Obata Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Kikuta Dental and Oral Medical Center, Kurume University School of Medicine Naoki Kaneko Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Kotaro Sato Department of Oral and Maxillofacial Surgery, Nagoya University, Graduate School of Medicine Norio Kitagawa Department of Oral and Maxillofacial Anatomy, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Yohei Takeshita Department of Oral and Maxillofacial Radiology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuhisa Matsuo Dental and Oral Medical Center, Kurume University School of Medicine Junsei Sameshima Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Akira Tachibana Department of Oral and Maxillofacial Surgery, Kakogawa Central City Hospital Shintaro Kawano Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Jingo Kusukawa Dental and Oral Medical Center, Kurume University School of Medicine Masaya Akashi Department of Oral and Maxillofacial Surgery, Kobe University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Joe Iwanaga Dental and Oral Medical Center, Kurume University School of Medicine Introduction: Although mandibular odontogenic deep neck infections are occasionally fatal, the transmission pathway has not been elucidated. Materials and Methods: This multicenter retrospective study was comprised of the patients of both sexes who were over 18 years of age and who had mandibular odontogenic deep neck abscesses. The patients' characteristics, laboratory tests, and radiographic findings were analyzed. Results: One hundred eighteen patients with mandibular odontogenic deep neck abscesses were included. Bone resorption superior to the mylohyoid line and the related abscess formation in submandibular space or submental space were both significantly associated with the presence of sublingual space abscess. In addition, the type of causative tooth was not a risk factor for abscess formation in both the sublingual space and “submandibular or submental” space. Conclusions: When an odontogenic lesion is located superior to the mylohyoid line, the abscess tends to initially form in the sublingual space and subsequently spread to the submandibular or submental space. Since any mandibular tooth can lead to abscess formation in these regions, oral and maxillofacial surgeons should carefully assess the anatomical position of the lesion and accurately identify the causative tooth. 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.

Wiley Acta Medica Okayama 0276-3478 2025 DSOK-0011 Potentially Regulates Circadian Misalignment and Affects Gut Microbiota Composition in Activity-Based Anorexia Model EN Hiroki Kawai Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nanami Wada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Sakamoto Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Miyazaki Sumitomo Pharma Co. Ltd Taro Kato Sumitomo Pharma Co. Ltd Yoshihiro Horiuchi Sumitomo Pharma Co. Ltd Hiroshi Kirii Department of Animal Applied Microbiology, Okayama University Graduate School of Environmental, Life, Natural Science and Technology Hoang Duy Nguyen Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Hinotsu Department of Neuropsychiatry, Okayama University Hospital Yoshio Ohya Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Asada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiyoshi Yokode Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Okahisa Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruko Miyazaki Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshitaka Oohashi Department of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Objective: Anorexia nervosa (AN) is a metabolic-psychiatric disorder characterized by severe weight loss, hypercortisolemia, and hypothalamic–pituitary–adrenal (HPA) axis activation. In this study, we investigated the effect of inhibiting cortisol regeneration via the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) on the pathophysiology of AN. Method: Female C57BL/6J mice underwent a 7-day activity-based anorexia (ABA) paradigm, involving 3 h daily feeding and free access to wheels, until 25% body weight loss or experiment completion. Mice were orally treated once daily with a potent 11β-HSD1 inhibitor, DSOK-0011, or vehicle. Body weight, food intake, and activity transitions were recorded; plasma corticosterone and cholesterol levels were measured using a fluorometric assay; gut microbiota were analyzed using 16S rRNA sequencing; and hippocampal glial cells were analyzed using immunohistochemistry. Results: DSOK-0011-treated mice exhibited a modest but significant increase in postprandial wheel-running activity compared to baseline (4–5 p.m., p = 0.018; 5–6 p.m., p = 0.043), whereas vehicle-treated mice showed higher preprandial activity (9–10 a.m., p = 0.0229). Gut microbiota analysis revealed increased alpha diversity in ABA mice, with a specific enrichment of the Lachnospiraceae family in the DSOK-0011 group. However, DSOK-0011 did not significantly affect body weight, food intake, corticosterone, and lipid levels, or hippocampal glial cell populations. Conclusion: Inhibition of 11β-HSD1 by DSOK-0011 was associated with microbiota alterations and subtle shifts in activity timing under energy-deficient conditions. These findings suggest that peripheral glucocorticoid metabolism may influence microbial and behavioral responses in the ABA model, although its metabolic impact appears limited in the acute phase. 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.

Wiley Acta Medica Okayama 1328-8067 67 1 2025 Early-life exposures and child health outcomes: A narrative review of LSN21 research in Japan e70258 EN Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Rumi Matsuo Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuka Yamamura Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Tsuge Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoka Kadowaki Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Uraguchi Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Tamai Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazue Nakamura Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihito Takeuchi Division of Neonatology, NHO Okayama Medical Center Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: The Longitudinal Survey of Newborns in the 21st Century (LSN21) tracks two Japanese national birth cohorts—2001 (baseline n = 47,010) and 2010 (n = 38,554)—from infancy through young adulthood, capturing parenting practices and family environments. Most studies analyze single exposures or outcomes. We conducted a narrative review summarizing the findings published by the Okayama University group on diverse health and developmental outcomes. Methods: We reviewed 59 LSN21 papers (2013–2025), extracting data on exposures, outcomes, and methods. Evidence was categorized into four exposure types (infant feeding, sleep, environmental, and perinatal) and three outcome domains (obesity, allergies/respiratory tract infections, and neurobehavioral development), including cohort comparisons. Results: Exclusive breastfeeding was associated with a lower obesity risk at ages 7 (adjusted odds ratio 0.55, 95% confidence interval 0.39–0.78) and 15, later puberty, and fewer hospitalizations. Short or irregular sleep before age 3 was linked to behavioral problems and injuries. Maternal smoking and prenatal air pollution were associated with respiratory conditions and developmental challenges. Preterm birth and small-for-gestational-age predicted delays, especially without catch-up growth by age 2. Pneumococcal vaccination likely contributed to declining otitis media after 2010. Additional findings included associations between outdoor play and reduced obesity risk, and complex relationships between breastfeeding and food allergies that varied by infantile eczema status. Conclusions: LSN21 findings highlight modifiable early-life factors (breastfeeding, sleep patterns, and smoke-free environments) and identify preterm and growth-restricted children for priority monitoring. While LSN21's strength lies in longitudinal social assessments, complementary perspectives from other Japanese cohorts could enhance understanding of biological mechanisms and intergenerational effects. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0385-5600 2025 PGN_0298 in the Assembly and Insertion Machinery (Aim) Operon Is Essential for the Viability of Porphyromonas gingivalis EN Shintaro Ono Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Katsuki Takebe Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ikue Tosa Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Nishiya Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University 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 Takayuki Wada Graduate School of Human Life and Ecology, Osaka Metropolitan University Shogo Takashiba Department of Pathophysiology–Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoya Ohara Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Porphyromonas gingivalis is a typical periodontal pathogen, and one of its key virulence factors is the powerful protease gingipains. Gingipains are secreted via the type IX secretion system (T9SS) and are associated with the assembly and insertion machinery (Aim) operon (PGN_0296 to PGN_0301), which encodes both T9SS components and non-T9SS proteins. In this study, we investigated PGN_0298, a gene of unknown function within this operon, to elucidate its role in P. gingivalis and to gain insights into its potential function through bioinformatics analyses. Our results demonstrated that PGN_0298 is essential for the viability of P. gingivalis, despite having limited direct association with T9SS. Sequence homology and structure predictions indicate that PGN_0298 encodes a putative isoprenyl transferase. The essentiality of PGN_0298 underscores its potential as a novel drug target for the treatment of periodontal disease. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0919-8172 32 11 2025 Role of Cytoreductive Nephrectomy in the Immune Checkpoint Inhibitor Era: A Multicenter Collaborative Study 1677 1685 EN Takuhisa Nukaya Department of Urology, Fujita-Health University School of Medicine Kiyoshi Takahara Department of Urology, Fujita-Health University School of Medicine Shingo Toyoda Department of Urology, Kindai University Faculty of Medicine Lan Inoki Department of Urology, Kindai University Faculty of Medicine Wataru Fukuokaya Department of Urology, The Jikei University School of Medicine Keiichiro Mori Department of Urology, The Jikei University School of Medicine Takehiro Iwata Department of Urology, Okayama University Graduate School of Medicine Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine Ryoichi Maenosono Department of Urology, Osaka Medical and Pharmaceutical University Takuya Tsujino Department of Urology, Osaka Medical and Pharmaceutical University Yosuke Hirasawa Department of Urology, Tokyo Medical University Takafumi Yanagisawa Department of Urology, The Jikei University School of Medicine Takeshi Hashimoto Department of Urology, Tokyo Medical University Kazumasa Komura Department of Urology, Osaka Medical and Pharmaceutical University Motoo Araki Department of Urology, Okayama University Graduate School of Medicine Kazutoshi Fujita Department of Urology, Kindai University Faculty of Medicine Yoshio Ohno Department of Urology, Tokyo Medical University Ryoichi Shiroki Department of Urology, Fujita-Health University School of Medicine Objectives: We aimed to evaluate overall survival (OS) and determine the optimal timing of cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC) receiving immune checkpoint inhibitor (ICI)-based therapy. Methods: This retrospective study reviewed medical records of 447 patients with mRCC treated with ICI at multiple Japanese institutions between January 2018 and August 2023. From this cohort, 178 patients with lymph node or distant metastases received either cytoreductive nephrectomy (CN group; n = 72) or ICI therapy without cytoreductive nephrectomy (non-CN group; n = 106) as first-line treatment. Results: Median progression-free survival was 15.7 months, and median overall survival was 58.1 months. CN significantly improved OS, with the CN group's median OS not reached, compared to 29.6 months in the non-CN group (p = 0.01). Deferred CN also showed improved survival outcomes. Poor prognostic factors for immediate CN included International Metastatic Renal Cell Carcinoma Database Consortium poor risk, sarcomatoid differentiation, and a high neutrophil-to-lymphocyte ratio. Conclusions: We developed a prognostic model to guide patient selection for CN, emphasizing the need for personalized treatment strategies. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0385-2407 2025 A Case of Netherton Syndrome/SPINK5-Syndromic Epidermal Differentiation Disorder Evaluated by Serial Tape-Stripping: Persistent Elevation of Serine Protease Activities Despite Clinical Improvement EN Shin Morizane 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 Ko Sunagawa 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 Ken‐Ichi Hasui Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, 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 No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1532-0626 37 27-28 2025 Algebraic Connectivity Maximizing Regular Graphs: Special Case Analysis and Depth‐First Search e70357 EN Masashi Kurahashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Najd Salaani Polytech Sorbonne, Sorbonne University Tsuyoshi Migita Faculty of Environmental, Life, Natural Science and Technology, Okayama University Norikazu Takahashi Faculty of Environmental, Life, Natural Science and Technology, Okayama University The algebraic connectivity is an indicator of how well connected a graph is. It also characterizes the convergence speed of some dynamic processes over networks. In this paper, taking into account that homogeneous networks are modeled as regular graphs, we tackle the following problem: given a pair (𝑛, 𝑘) of positive integers such that 𝑘 is less than 𝑛 and kn is an even number, find a 𝑘-regular graph with 𝑛 vertices that have the maximum algebraic connectivity. We first consider some special cases and derive solutions through theoretical analysis. We next present depth-first search algorithms for solving the problem, which reduce the search space by making use of some known properties of the regular graph and the algebraic connectivity.We also show the results of execution of the proposed algorithms for the values of 𝑛 up to 12. 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.

Wiley Acta Medica Okayama 1752-8054 18 10 2025 Effectiveness of Statins for Oxaliplatin‐Induced Peripheral Neuropathy: A Multicenter Retrospective Observational Study e70318 EN Kenshi Takechi Department of Drug Information Analysis, College of Pharmaceutical Sciences, Matsuyama University Takehiro Kawashiri Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University Keisuke Mine Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University Soichiro Ushio Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Noriko Hida Department of Clinical Research and Development, Graduate School of Pharmacy, SHOWA Medical University Kenji Momo Department of Hospital Pharmaceutics, Graduate School of Pharmacy, SHOWA Medical University Masanobu Uchiyama Department of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Mami Uchida Department of Pharmacy, Fukuoka University Hospital Mamoru Tanaka Division of Pharmacy, Ehime University Hospital Noriaki Hidaka Division of Pharmacy, Ehime University Hospital Hideki Yasui Center for Clinical Research, Hamamatsu University Hospital Masahiro Ueda Faculty of Pharmaceutical Sciences, Setsunan University Ryohei Fujii Department of Pharmacy, Kansai Medical University Hospital Misaki Hashimoto Department of Pharmacy, Kansai Medical University Hospital Yasutaka Sakamoto Department of Pharmacy, Yokohama City University Hospital Kana Uyama Department of Pharmacy, Yokohama City University Hospital Takahiro Niimura Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences Yuki Hanai Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University Ayaka Tsuboya Department of Pharmacy, Kawasaki Municipal Tama Hospital Keisuke Suzuki Innovation Center for Translational Research, National Center for Geriatrics and Gerontology Naoya Kamiyama Asahikawa Medical University Hospital Hiromi Hagiwara Nagoya City University Hospital Naoto Okada Pharmacy Department, Yamaguchi University Hospital Yoshito Zamami Department of Pharmacy, Okayama University Hospital Keisuke Ishizawa Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences Chemotherapy-induced peripheral neuropathy, including oxaliplatin-induced peripheral neuropathy (OIPN), can have a negative impact on patient quality of life for months or even years after discontinuation of chemotherapy. Statins are commonly used for lowering cholesterol; however, evidence indicates that statins have multiple pleiotropic effects. Although statins are anticipated to exert neuroprotective actions against OIPN, no large-scale investigations have been conducted in real-world clinical settings. Our investigation aimed to determine if statins protected against OIPN. This multicentre retrospective study enrolled Japanese patients with cancer, including those with colorectal cancer (CRC), who received oxaliplatin-containing chemotherapy between April 2009 and December 2019. Propensity score matching between groups was performed to assess the relationship between the occurrence of OIPN and statin use. Among the examined 2657 patients receiving oxaliplatin, 24.7% had Grade ≥ 2 OIPN. There was no significant difference in the incidence of OIPN between the statin and non-statin groups, even after propensity score matching. However, among the matched patients with CRC (n = 510), statin use was associated with a significantly lower incidence of Grade ≥ 2 OIPN than no statin use (19.8% vs. 28.3%, respectively; p = 0.029). Our findings indicate that statins may protect against OIPN in patients with CRC. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1086-9379 2025 The effect of pressure on dihedral angle between liquid Fe‐S and orthopyroxene: Implication for percolative core formation in planetesimals and planetary embryos EN Takumi Miura Department of Earth and Space Science, Osaka University Hidenori Terasaki Department of Earth Sciences, Okayama University Hyu Takaki Department of Earth Sciences, Okayama University Kotaro Kobayashi Department of Earth Sciences, Okayama University Geoffrey David Bromiley School of Geosciences, The University of Edinburgh Takashi Yoshino Institute for Planetary Materials, Okayama University During precursor stages of planet formation, many planetesimals and planetary embryos are considered to have differentiated, forming an iron-alloy core and silicate mantle. Percolation of liquid iron-alloy in solid silicates is one of the major possible differentiation processes in these small bodies. Based on the dihedral angles between Fe-S melts and olivine, a criterion for determining whether melt can percolate through a solid, it has been reported that Fe-S melt can percolate through olivine matrices below 3 GPa in an oxidized environment. However, the dihedral angle between Fe-S melts and orthopyroxene (opx), the second most abundant mineral in the mantles of small bodies, has not yet been determined. In this study, high-pressure and high-temperature experiments were conducted under the conditions of planetesimal and planetary embryo interiors, 0.5–5.0 GPa, to determine the effect of pressure on the dihedral angle between Fe-S melts and opx. Dihedral angles tend to increase with pressure, although the pressure dependence is markedly reduced above 4 GPa. The dihedral angle is below the percolation threshold of 60° at pressures below 1.0–1.5 GPa, indicating that percolative core formation is possible in opx-rich interiors of bodies where internal pressures are lower than 1.0–1.5 GPa. The oxygen content of Fe-S melt decreases with increasing pressure. High oxygen contents in Fe-S melt reduce interfacial tension between Fe-S melt and opx, resulting in reduced dihedral angles at low pressure. Combined with previous results for dihedral angle variation of the olivine/Fe-S system, percolative core formation possibly occurs throughout bodies up to a radius of 1340 km for an olivine-dominated mantle, and up to 770 km for an opx-dominated mantle, in the case of S-rich cores segregating under relatively oxidizing conditions. For mantles of small bodies in which abundant olivine and opx coexist, the mineral with the largest volume fraction and/or smallest grain size will allow formation of interconnected mineral channels, and, therefore, the wetting property of this mineral determines the wettability of the melt, that is, controls core formation. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2328-9503 2025 INF2-Related Charcot–Marie–Tooth Disease in a Japanese Cohort: Genetic and Clinical Insights EN Chikashi Yano Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Masahiro Ando Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Yujiro Higuchi Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Jun‐Hui Yuan Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Akiko Yoshimura Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Takahiro Hobara Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Risa Nagatomo Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Fumikazu Kojima Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Yu Hiramatsu Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Satoshi Nozuma Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Tomonori Nakamura Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Yusuke Sakiyama Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Chika Matsuoka Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Kimura Department of Neurology, Hyogo Medical University Ayako Miyazaki Department of Clinical Genetics, Hyogo Medical University Chinatsu Kinjo Department of Clinical Genetics, Hyogo Medical University Kenji Yokochi Department of Pediatrics, Toyohashi Municipal Hospital Nanami Yamanaka Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine Nozomu Matsuda Department of Neurology, Fukushima Medical University School of Medicine Tomoki Suichi Department of Neurology, Graduate School of Medicine, Chiba University Yoshiyuki Hanaoka Department of Pediatrics, Kurashiki Central Hospital Haruka Kojima Department of Neurology, Tokyo Women's Medical University Kenichi Todo Department of Neurology, Tokyo Women's Medical University Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Mitsui Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Shoji Tsuji Department of Neurology, The University of Tokyo Hospital Hiroshi Takashima Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Background: INF2 mutations cause focal segmental glomerulosclerosis (FSGS) and Charcot–Marie–Tooth disease (CMT). Accurate genetic diagnosis is critical, as INF2-related FSGS is typically resistant to immunotherapy yet rarely recurs after transplantation, and its associated neuropathy can mimic treatable immune-mediated disorders such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Methods: We performed a multicenter study investigating 3329 Japanese patients with inherited peripheral neuropathies/CMT who underwent gene panel sequencing or whole-exome analysis between 2007 and 2024. Clinical data, including electrophysiological assessments, were obtained from the patients' medical records. Results: We identified six pathogenic INF2 variants in eight patients, all of which were located within the diaphanous inhibitory domain. Structural modeling revealed clustering of variants near the diaphanous autoregulatory domain-binding pocket, which is critical for INF2 autoinhibition. Clinically, all cases were sporadic, with a median age at neurological onset of 9 years. All patients exhibited lower limb weakness, and 6/8 (75%) had sensory disturbances. All patients also developed kidney dysfunction, with 7/8 (88%) progressing to end-stage renal disease at a median age of 15 years. Furthermore, all patients showed demyelinating neuropathy, and 2/8 (25%) received immunotherapy due to suspected immune-mediated neuropathy. Conclusion: Although INF2 variants are a rare cause of CMT in Japan, they should be considered in pediatric patients with demyelinating neuropathy and early-onset proteinuria, even in the absence of a family history. Blood and urine tests assessing renal dysfunction can provide guidance for appropriate genetic testing. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0013-8703 2025 Artificial Selections for Life-History Traits Affect Effective Cumulative Temperature and Developmental Zero Point in Zeugoducus cucurbitae EN Takahisa Miyatake Graduate School of Environment, Life, Natural Science and Technology, Okayama University Kentarou Matsumura Department of General Systems Studies, Graduate School of Arts and Sciences, the University of Tokyo Effective cumulative temperature and developmental zero point are important indicators for estimating the timing of organism development and the area of distribution. These indicators are generally considered to have unique values for different species of organisms and are also important for predicting the distribution range of animals and plants, especially insect pests. These values generally are species-specific, but there is variation within populations in traits having a genetic component. However, there are no studies on what kind of selection pressure affects these indicator values. To address this issue, it would be worthwhile to compare these values using individuals of strains that have been artificially selected for life-history traits by rearing them at various temperatures and calculating these indicators from developmental days and temperatures. In the present study, eggs were taken from adults of strains with many generations of artificial selection on two life-history traits (age at reproduction and developmental period) of the melon fly, Zeugodacus cucurbitae, under constant temperature conditions. Eggs were reared at five different temperatures, and the effective cumulative temperatures and developmental zero points of the larval and developmental periods were compared. The results demonstrate that artificial selection on life-history traits in Z. cucurbitae induces evolutionary changes in both the effective cumulative temperature and the developmental zero point across successive generations. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0960-7412 123 5 2025 RNA processing/modifying enzymes play key roles in the response to thermospermine in Arabidopsis thaliana e70476 EN Mitsuru Saraumi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takahiro Tanaka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Daiki Koyama Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshitaka Nishi Graduate School of Engineering, Kyushu Sangyo University Yoshihiro Takahashi Department of Life Science, Faculty of Life Science, Kyushu Sangyo University Hiroyasu Motose Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Taku Takahashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Thermospermine is involved in negative regulation of xylem differentiation by enhancing the translation of mRNAs of the SAC51 gene family in Arabidopsis (Arabidopsis thaliana). These mRNAs contain conserved upstream open reading frames (uORFs) that interfere with the translation of the main ORF. To investigate the mechanism by which thermospermine acts in this process, we isolated mutants insensitive to thermospermine, named ‘its’. We show that the four genes responsible for these mutants, its1 to its4, encode: (i) a homolog of SPOUT RNA methyltransferase, (ii) an rRNA pseudouridine synthase CBF5/NAP57, (iii) a putative spliceosome disassembly factor STIPL1/NTR1, and (iv) a plant-specific RNA-binding protein PHIP1. These four mutants were found to have much higher levels of thermospermine than the wild-type. While all these mutants except its1 appear almost normal, they enhance the dwarf phenotype of a mutant of ACL5, which encodes thermospermine synthase, resulting in tiny plants resembling a double knockout of ACL5 and SACL3, a member of the SAC51 family. Reporter assays revealed that GUS activity from the CaMV 35S promoter-SAC51 5′-GUS fusion construct was significantly reduced in its1 and its4 or not affected in its2 and its3, while it was slightly increased in its1, its3, and its4, or not changed in its2 by thermospermine. These findings underscore the critical role of RNA processing and modification in the thermospermine-dependent translational regulation of uORF-containing transcripts. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1367-2223 28 1 2024 Can online interactions reduce loneliness in young adults during university closures in Japan? The directed acyclic graphs approach e12658 EN Kohei Kambara Doshisha University Akihiro Toya Hiroshima University Sumin Lee Hiroshima University Haruka Shimizu Nishikyushu Univ. Junior College Kazuaki Abe Hiroshima University Jun Shigematsu Toyama University Qingyuan Zhang Hiroshima University Natsuki Abe Hiroshima Bunkyo University Ryo Hayase Chubu University Nobuhito Abe Kyoto University Ryusuke Nakai Kyoto University Shuntaro Aoki Fukushima Medical University Kohei Asano Kyoto University Ryosuke Asano Kurume University Makoto Fujimura Fukuoka Jo Gakuin University Ken’ichiro Fukui Kwassui Women's University Yoshihiro Fukumoto Kansai Medical University Kaichiro Furutani Kansai University Koji Hasegawa Komazawa University Hirofumi Hashimoto Osaka Metropolitan University Mikoto Hashimoto Chukyo Gakuin University Hiroki Hosogoshi Kansai University Hiroshi Ikeda Kyushu University Toshiyuki Ishioka Kobe University Chiharu Ito University of Human Environments Suguru Iwano Fukushima Medical University Masafumi Kamada Shujitsu Junior College Yoshihiro Kanai Tohoku Gakuin University Tomonori Karita Ehime University Yu Kasagi Rissho University Emiko S. Kashima La Trobe University Juri Kato Kanazawa Institute of Technology Yousuke Kawachi Tohoku University Jun‐ichiro Kawahara Hokkaido University Masanori Kimura Graduate School of Business Administration, Kobe University Yugo Kira Kurume University Yuko Kiyonaga (Sakoda) Kyushu Kyoritsu University Hiroshi Kohguchi Ryutsu Keizai University Asuka Komiya Hiroshima University Keita Masui Otemon Gakuin University Akira Midorikawa Chuo University Nobuhiro Mifune Kochi University of Technology Akimine Mizukoshi Asahi University Kengo Nawata Fukuoka University Takashi Nishimura Hiroshima International University Daisuke Nogiwa Seikei University Kenji Ogawa Hokkaido University Junko Okada Prefectural University of Hiroshima Aki Okamoto Okayama University Reiko Okamoto Osaka University Kyoko Sasaki Kanagawa University of Human Services Kosuke Sato Kurume University Hiroshi Shimizu Kwansei Gakuin University Atsushi Sugimura Tokai University Yoko Sugitani Sophia University Hitomi Sugiura Kindai University Kyoko Sumioka Okayama University Bumpei Sunaguchi Graduate School of Business Administration, Kobe University Masataka Takebe Otsuma Women's University Hiroki C. Tanabe Nagoya University Ayumi Tanaka Doshisha University Masanori Tanaka Hokkai‐Gakuen University Junichi Taniguchi Tezukayama University Namiji Tokunaga Ehime Prefectural University of Health Sciences Ryozo Tomita Musashino University Yumiko Ueda Asahi University Tomomi Yamashita Jumonji University Kazuho Yamaura Ritsumeikan University Masao Yogo Doshisha University Kenji Yokotani Tokushima University Ayano Yoshida Tohoku Fukushi University Hiroaki Yoshida Shinshu University Katsue Yoshihara Fukuoka Institute of Technology Junior College Ayumi Yoshikawa Osaka Dental University Faculty of Nursing Kuniaki Yanagisawa Kobe University Ken'ichiro Nakashima Hiroshima University As a countermeasure to the increased loneliness induced by the COVID-19 pandemic-related university closures, universities provided students with online interaction opportunities. However, whether these opportunities contributed to reducing loneliness during the university closures remains unclear, as previous studies have produced contradictory findings. We conducted a nationwide cross-sectional survey. Data were collected on demographics, social environment, social support, interactions, health and loneliness from 4949 students from 60 universities across Japan. We used psychological network and Directed Acyclic Graphs (DAGs) to examine the effect of online interactions on loneliness during university closures during COVID-19. The results showed that the frequency of online interactions with friends did not exert a significant influence on loneliness during university closures. A comparative examination of the DAGs further illuminated that the social environment exhibited fewer pathways for interpersonal interactions and social support during these closure periods. The psychosocial pathways influencing young adults' loneliness show variations contingent on the university's closure status. Notably, the impact of heightened online interactions with friends on loneliness appears to be less pronounced among young adults in the context of university closure. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0912-3814 40 4 2024 Nationwide diversity of symbolic “city flowers” in Japan is increasing 463 474 EN Yoichi Tsuzuki Health and Environmental Risk Division, National Institute for Environmental Studies Haruna Ohsaki Department of Biological Sciences, Tokyo Metropolitan University Yawako W. Kawaguchi Department of Biological Sciences, Graduate School of Science, The University of Tokyo Sayaka Suzuki Center for Ecological Research, Kyoto University Shogo Harada Department of Biology, Graduate School of Science, Osaka City University Yurie Otake Center for Ecological Research, Kyoto University Naoto Shinohara Center for Ecological Research, Kyoto University Koki R. Katsuhara Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Recognizing and maintaining locally rooted human–nature interactions is essential for utilizing ecosystem services. Although the general public's awareness of biodiversity and ecosystem services has been examined using various proxies, it remains unclear how local governments—key sectors in creating conservation policies—appreciate them within a solid local context. Here, we focused on the “city flower,” an official symbolic species of Japanese cities, as a new proxy for measuring governmental attitudes toward biota and its services. We aimed to capture temporal changes in the awareness of species with locally relevant value at the city government level by examining the changes in city flowers over more than half a century. Data from the official websites of municipalities, including the names, the adoption years, and the reasons for adoption, revealed two major periods of adoption, with a notable increase in species diversity in and after 1993. This increase could be attributed to a recent reduction in bias toward popular flowers and growing interest in alternative, less popular flowers. Analysis of the reasons for adoption suggested that the temporal change in adopted flower species was related to the increasing emphasis on species with an explicit local context, especially those with instrumental value to the city. Our findings indicate the tendency for local governments to increasingly recognize their biocultural backgrounds and the ecosystem services of plants within their regions. The growing awareness of the local governments regarding their biocultural background is a positive sign for the conservation of biodiversity and ecosystem services. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1344-3941 96 1 2025 Presence of a Deletion Mutation of Myostatin (MSTN) Gene Associated With Double-Muscling Phenotype in Japanese Black Cattle Population e70055 EN Nu Anh Thu Le Faculty of Veterinary Medicine Okayama University of Science Imabari Rena Kubo Faculty of Veterinary Medicine Okayama University of Science Imabari Liushiqi Borjigin Faculty of Veterinary Medicine Okayama University of Science Imabari Takayuki Ibi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Shinji Sasaki Faculty of Agriculture Ryukyu University Nishihara Tetsuo Kunieda Faculty of Veterinary Medicine Okayama University of Science Imabari Mutations in the bovine myostatin (MSTN) gene have been identified as the causative factor for the double-muscling phenotype in several European cattle breeds, including Belgian Blue, Piedmontese, and Shorthorn. In Japan, following the Meiji Restoration, several European breeds, including Shorthorn, Brown Swiss, Devon, Simmental, and Ayrshire, were introduced and crossbred with native cattle to develop modern Japanese beef cattle breeds, such as Japanese Black cattle. Historical records regarding the breeding of Japanese Black cattle indicate that the double-muscling phenotype, referred to as “Butajiri,” occasionally appeared in Japanese Black cattle population. These historical observations suggest the potential presence of MSTN gene mutation in the Japanese Black cattle population. The aim of this study was, therefore, to investigate the presence of MSTN gene mutation in the current Japanese Black cattle population. Through screening 400 reproductive females, we identified one cow carrying an 11-bp deletion in the MSTN gene. While further investigation of the animals in the pedigree of this cow could not reveal any living animals with this mutation, this is the first report demonstrating the presence of the MSTN mutation in the Japanese Black cattle population. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1936-5209 19 3 2025 Oregon Wolfe barley genetic stocks – Research and teaching tools for next generation scientists e70004 EN Margaret R. Krause Department of Crop and Soil Science, Oregon State University Juan David Arbelaez Department of Crop Sciences, University of Illinois at Urbana-Champaign Åsmund Asdal Nordic Genetic Resource Centre Ramzi Belkodja CIHEAM-Zaragoza Nancy Boury Department of Plant Pathology, Entomology, and Microbiology, Iowa State University Victoria C. Blake Department of Plant Sciences and Plant Pathology, Montana State University Patrick J. Brown Department of Plant Sciences, University of California-Davis Ana Casas Departamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSIC Luis Cistué Departamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSIC Alba Farré‐Martínez AGROTECNIO-CERCA Center, Universidad de Lleida Scott Fisk Department of Crop and Soil Science, Oregon State University Gregory S. Fuerst U.S. Department of Agriculture-Agricultural Research Service, Corn Insects and Crop Genetics Research Unit, Iowa State University Estela Giménez Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid Carla Guijarro‐Real Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid Katy Guthrie Department of Agronomy and Plant Genetics, University of Minnesota Margaret Halstead Aardevo North America Laura Helgerson Department of Crop and Soil Science, Oregon State University Hiroshi Hisano Institute of Plant Science and Resources, Okayama University Ernesto Igartua Departamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSIC Morten Lillemo Department of Plant Sciences, Norwegian University of Life Sciences Marina Martínez‐García Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid Mariona Martínez‐Subirà AGROTECNIO-CERCA Center, Universidad de Lleida Susan McCouch Plant Breeding and Genetics Section, School of Integrative Plant Science, Cornell University Laurie McGhee Colfax-Mingo Community High School Travis Nickols Department of Crop and Soil Science, Oregon State University Nick Peters Department of Plant Pathology, Entomology, and Microbiology, Iowa State University Raymond Porter Haupert Institute for Agricultural Studies, Huntington University Ignacio Romagosa AGROTECNIO-CERCA Center, Universidad de Lleida Anja Karine Ruud Department of Plant Sciences, Norwegian University of Life Sciences Kazuhiro Sato Institute of Plant Science and Resources, Okayama University Silvio Salvi Department of Agricultural and Food Sciences, University of Bologna Giuseppe Sangiorgi Department of Agricultural and Food Sciences, University of Bologna Rebekka Schüller Department of Crop Sciences, University of Illinois at Urbana-Champaign Taner Z. Sen Crop Improvement and Genetics Research Unit, U.S. Department of Agriculture-Agricultural Research Service José Miguel Soriano AGROTECNIO-CERCA Center, Universidad de Lleida Robert M. Stupar Department of Agronomy and Plant Genetics, University of Minnesota To‐Chia Ting Agronomy Department, Purdue University Kelly Vining Department of Crop and Soil Science, Oregon State University Maria von Korff Institute of Plant Genetics, Heinrich-Heine-Universität Düsseldorf Agatha Walla Institute of Plant Genetics, Heinrich-Heine-Universität Düsseldorf Diane R. Wang Agronomy Department, Purdue University Robbie Waugh Division of Plant Sciences, School of Life Sciences, University of Dundee Roger P. Wise Department of Plant Pathology, Entomology, and Microbiology, Iowa State University Robert Wolfe Agriculture and Agri-Food Canada Eric Yao Crop Improvement and Genetics Research Unit, U.S. Department of Agriculture-Agricultural Research Service Patrick M. Hayes Department of Crop and Soil Science, Oregon State University The Oregon Wolfe Barley (OWB) mapping population (Reg. no. MP-4, NSL 554937 MAP) is a resource for genetics research and instruction. The OWBs are a set of doubled haploid barley (Hordeum vulgare L.) lines developed at Oregon State University from the F1 of a cross between Dr. Robert Wolfe's dominant and recessive marker stocks. Exhibiting a high level of genetic and phenotypic diversity, the OWBs are used throughout the world as a research tool for barley genetics. To date, these endeavors have led to 56 peer-reviewed publications, as well as three reports in the Barley Genetics Newsletter. At the same time, the OWBs are widely used as an instructor resource at the K–12, undergraduate, graduate, and professional levels. They are currently used at universities and/or institutes in German, Italy, Norway, Spain, and the United States and are currently being developed further for educational use in other countries. Genotype and phenotype data, lesson plans, and seed availability information are available herein and online. 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.

Wiley Acta Medica Okayama 0021-8901 2025 Urbanised landscape and microhabitat differences can influence flowering phenology and synchrony in an annual herb EN Hinata Fujiwara Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroto Yamaguchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuyoshi Nakata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koki R. Katsuhara Graduate School of Environmental, Life, Natural Science and Technology, Okayama University 1. Flowering phenology, a crucial determinant of plant reproductive success and biotic interactions, is susceptible to urbanisation. Numerous studies have shown the impact of urbanised landscapes on flowering phenology based on comparisons along urban–rural gradients. Phenological patterns among microenvironments in the urban ecosystem have received less attention, although they often offer unique habitats with varying artificial influences, such as roadsides, drainage ditches and vacant lots. If differences in microenvironments diversify flowering phenology, the urban matrix might reduce flowering synchrony with neighbouring populations, limiting outcrossing opportunities and therefore reducing reproductive success. 2. We investigated the flowering phenology and synchrony of the native annual herb Commelina communis in approximately 250 populations at two rural and two urban sites over 3 years. To determine the effect of microhabitat differences, we categorised the microhabitats of C. communis populations into five types: drains, roadsides, vacant land, farmland and forest edge. In some study populations, we investigated reproductive success (seed set) to estimate the degree of outcross pollination limitation. 3. Our findings revealed that populations in urban sites exhibited earlier flowering onset and longer flowering duration compared to rural locations. Besides, we did not detect consistent patterns of flowering onset, peak and duration among the different microhabitat types. For flowering synchrony, we found that the population in urban sites, growing in drain habitats, and with artificial disturbances exhibited relatively lower interpopulation flowering synchrony, suggesting their phenology differed from neighbouring populations within the same landscape. Additionally, populations in urban sites, especially those growing in drain and roadside habitats, suffered severe outcross pollen limitation compared to those in rural landscapes. 4. Synthesis and applications. In conclusion, our results indicate that in addition to landscape changes associated with urbanisation, variations in local microhabitats also influence the flowering phenology and synchrony of C. communis populations. Urbanised landscapes and differences in microhabitats could contribute to the diversification of phenological patterns between populations, potentially having a negative impact on the reproductive success of native plant species. These findings highlight the need to consider not only spatial but also temporal fragmentation from diversified flowering phenology when addressing conservation in the urban matrix. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1758-5902 18 1 2025 Clinical Impacts of Minimally Invasive Transperineal Abdominoperineal Resection in Crohn's Disease: A Retrospective Analysis e70149 EN Yoshitaka Kondo 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 Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshihiro Inokuchi Research Center for Intestinal Health Science, Okayama University Sakiko Hiraoka Department of Gastroenterology and Hepatology, 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 Yuki Matsumi 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 Fuminori Teraishi 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 Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction: Crohn's disease (CD) often leads to complex anorectal complications, posing significant challenges in surgical management. Transperineal abdominoperineal resection (TpAPR) has emerged as a minimally invasive alternative to APR. This study aims to evaluate the safety and efficacy of TpAPR compared to APR in patients with CD. Methods: A retrospective analysis was conducted on 19 CD patients who underwent either minimally invasive TpAPR (n = 11) or APR (n = 8) between 2008 and 2023 from a single institution. The primary outcomes were assessed: intraoperative blood loss, operative time, and surgical site infection (SSI) rates. Results: The minimally invasive TpAPR group exhibited significantly reduced intraoperative blood loss (223 mL vs. 533 mL, p = 0.04) and a lower incidence of SSI rates (36.4% vs. 75%, p = 0.07). Operative time and hospital stay were comparable between groups. Conclusion: Minimally invasive TpAPR demonstrates potential benefits over APR in reducing blood loss and SSI rates in CD patients. Further large-scale studies are warranted to confirm these findings. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0915-5635 2025 Vendor‐Agnostic Vision Transformer‐Based Artificial Intelligence for Peroral Cholangioscopy: Diagnostic Performance in Biliary Strictures Compared With Convolutional Neural Networks and Endoscopists EN Ryosuke Sato Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Masahiro Tomiya Healthcare Solutions Division, Ryobi Systems Co., Ltd Takayoshi Tanimoto Healthcare Solutions Division, Ryobi Systems Co., Ltd Akimitsu Ohto Healthcare Solutions Division, Ryobi Systems Co., Ltd Kentaro Oki Department of Gastroenterology and Hepatology, Okayama University Hospital Satoshi Kajitani Department of Gastroenterology and Hepatology, Okayama University Hospital Tatsuya Kikuchi Department of Gastroenterology and Hepatology, Okayama University Hospital Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuya Miyamoto 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 Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Yoshiro Kawahara Department of Gastroenterology and Hepatology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Objectives: Accurate diagnosis of biliary strictures remains challenging. This study aimed to develop an artificial intelligence (AI) system for peroral cholangioscopy (POCS) using a Vision Transformer (ViT) architecture and to evaluate its performance compared to different vendor devices, conventional convolutional neural networks (CNNs), and endoscopists. Methods: We retrospectively analyzed 125 patients with indeterminate biliary strictures who underwent POCS between 2012 and 2024. AI models including the ViT architecture and two established CNN architectures were developed using images from CHF-B260 or B290 (CHF group; Olympus Medical) and SpyScope DS or DS II (Spy group; Boston Scientific) systems via a patient-level, 3-fold cross-validation. For a direct comparison against endoscopists, a balanced 440-image test set, containing an equal number of images from each vendor, was used for a blinded evaluation. Results: The 3-fold cross-validation on the entire 2062-image dataset yielded a robust accuracy of 83.9% (95% confidence interval (CI), 80.9–86.7) for the ViT model. The model's accuracy was consistent between CHF (82.7%) and Spy (86.8%, p = 0.198) groups, and its performance was comparable to the evaluated conventional CNNs. On the 440-image test set, the ViT's accuracy of 78.4% (95% CI, 72.5–83.8) was comparable to that of expert endoscopists (82.0%, p = 0.148) and non-experts (73.0%, p = 0.066), with no statistically significant differences observed. Conclusions: The novel ViT-based AI model demonstrated high vendor-agnostic diagnostic accuracy across multiple POCS systems, achieving performance comparable to conventional CNNs and endoscopists evaluated in this study. 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.

Wiley Acta Medica Okayama 0020-7594 60 4 2025 When Confidence in Institutions Backfires: Power‐Distance Orientation Moderates the Relationship Between Institutional Trust and Civic Honesty Across Eight Countries e70059 EN Silvana D'Ottone School of Psychology, Pontificia Universidad Católica de Chile Giovanni A. Travaglino Institute for the Study of Power, Crime and Society, Department of Law and Criminology, Royal Holloway University of London Pascal Burgmer School of Psychology, University of Southampton Isabella Giammusso Department of Psychology, Educational Science and Human Movement, University of Palermo Hirotaka Imada Institute for the Study of Power, Crime and Society, Department of Law and Criminology, Royal Holloway University of London Yanhui Mao Institute of Applied Psychology, Psychological Research and Counseling Center, Southwest Jiaotong University Alberto Mirisola Department of Psychology, Educational Science and Human Movement, University of Palermo Chanki Moon Institute for the Study of Power, Crime and Society, Department of Law and Criminology, Royal Holloway University of London Kengo Nawata Faculty of Humanities, Fukuoka University Miki Ozeki Faculty of Humanities and Social Sciences, Okayama University Confidence in institutions is a key predictor of civic honesty, yet evidence shows that this relationship varies across contexts and individuals. This study examined whether power-distance orientation (PDO)—the extent to which individuals accept hierarchical power relations—moderates this association. High-PDO individuals tend to view institutional authorities as entitled to privilege, inclined to engage in patronage relationships and potentially corrupt. We hypothesised that for individuals high in PDO, confidence in institutions could backfire and be linked to the rejection of civic honesty. Using data from 2088 participants across eight countries, we found support for this hypothesis. Specifically, the positive link between institutional confidence and civic honesty was reversed among those who strongly endorse PDO. These findings suggest that individual-level variation in the link between confidence in institutions and civic honesty partly reflects broader beliefs about authorities. We discuss implications of this interaction and outline directions for future research. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2692-4609 6 1 2025 Adequacy evaluation of 22‐gauge needle endoscopic ultrasound‐guided tissue acquisition samples and glass slides preparation for successful comprehensive genomic profiling testing: A single institute experience e70104 EN Tami Nagatani Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoji Wani Department of Pathology, Japanese Red Cross Society, Himeji Red Cross Hospital Masahiro Takatani Department of Internal Medicine, Japanese Red Cross Society, Himeji Red Cross Hospital Soichiro Fushimi Department of Pathology, Japanese Red Cross Society, Himeji Red Cross Hospital Hirofumi Inoue Division of Medical Support, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Shinichiro Hori Department of Internal Medicine, Japanese Red Cross Society, Himeji Red Cross Hospital Kyohei Kai Department of Genetic Medicine, Japanese Red Cross Society, Himeji Red Cross Hospital Hideki Yamamoto Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Okazaki Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Maki Tanioka Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Internal Medicine, Japanese Red Cross Society, Himeji Red Cross Hospital Akira Hirasawa Clinical Genomic Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objectives: This study aimed to evaluate the successful sequencing rate of Foundation One CDx (F1CDx) using small tissue samples obtained with a 22-gauge needle (22G) through endoscopic ultrasound-guided fine needle acquisition (EUS-TA) and to propose guidelines for tissue quantity evaluation criteria and proper slide preparation in clinical practice. Methods: Between June 2019 and April 2024, 119 samples of 22G EUS-TA collected for F1CDx testing at Himeji Red Cross Hospital were retrospectively reviewed. Tissue adequacy was only assessed based on tumor cell percentage (≥20%). The procedure stopped when white tissue fragments reached 20 mm during macroscopic on-site evaluation. The specimens were prepared using both ‘tissue preserving sectioning’ to retain tissue within formalin-fixed paraffin-embedded blocks and the ‘thin sectioning matched needle gauge and tissue length’ method with calculation to ensure minimal unstained slides for the 1 mm3 sample volume criterion. Tissue area from HE slides and sample volume were measured, and F1CDx reports were analyzed. Results: Of 119 samples, 108 (90.8%) were suitable for F1CDx. Excluding the cases not submitted for testing, in the 45 cases where F1CDx was done using 22G EUS-TA samples, eight (17.8%) had a sum of tissue area tissue of 25 mm2 or greater in the HE-stained sample. However, all cases met the F1CDx 1 mm3 volume criterion by submitting > 30 unstained slides per sample. As a result, 43 of 45 cases (95.6%) were successfully analyzable. Conclusions: The 22G EUS-TA needle is an effective tool for providing the sufficient tissue volume required for F1CDx. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0953-4180 2024 2024 Mice Recognise Mice in Neighbouring Rearing Cages and Change Their Social Behaviour 9215607 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Mice are social animals that change their behaviour primarily in response to visual, olfactory, and auditory information from conspecifics. Rearing conditions such as cage size and colour are important factors influencing mouse behaviour. In recent years, transparent plastic cages have become standard breeding cages. The advantage of using a transparent cage is that the experimenter can observe the mouse from outside the cage without touching the cage. However, mice may recognise the environment outside the cage and change their behaviour. We speculated that mice housed in transparent cages might recognise mice in neighbouring cages. We used only male mice in this experiment. C57BL/6 mice were kept in transparent rearing cages with open lids, and the cage positions were maintained for 3 weeks. Subsequently, we examined how mice behaved toward cagemate mice, mice from neighbouring cages, and mice from distant cages. We compared the level of interest in mice using a social preference test. Similar to previous reports, subject mice showed a high degree of interest in unfamiliar mice from distant cages. By contrast, subject mice reacted to mice from neighbouring cages as familiar mice, similar to cagemate mice. This suggests that mice housed in transparent cages with open lids perceive the external environment and identify mice in neighbouring cages. Researchers should pay attention to the environment outside the mouse cage, especially for the social preference test. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2769-2558 4 3 2025 Occupational therapist‐guided exercise increased white blood cell and neutrophil counts during clozapine treatment: A case report e70167 EN Kenji Hinotsu Department of Neuropsychiatry, Okayama University Hospital Shinji Sakamoto Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Kawai Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshio Ohya Department of Neuropsychiatry, Okayama University Hospital Akiyoshi Yokode Department of Neuropsychiatry, Okayama University Hospital Takahiro Asada Department of Neuropsychiatry, Okayama University Hospital Yuko Okahisa Department of Neuropsychiatry, Okayama University Hospital Manabu Takaki Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Background: Moderate exercise increases white blood cells and neutrophils. However, there are no reports on the relationship between exercise intensity and these cells. We observed a patient taking clozapine whose white blood cell and neutrophil counts were borderline. Supervised exercise therapy with an occupational therapist stabilized these counts. Case Presentation: A 50-year-old woman with treatment-resistant schizophrenia was prescribed clozapine. By Day 63, the clozapine dosage had been increased to 450 mg/day. Additionally, she was advised to perform a 30-min walking exercise program 1 h before blood tests. Exercise therapy supervised by an occupational therapist was performed eight times, and self-training was performed five times. Exercise intensity was monitored using the Borg Scale for subjective evaluation and the Karvonen formula for objective evaluation. Supervised exercise therapy with an occupational therapist resulted in greater increases on the Borg Scale and Karvonen formula than did self-training. It also induced increases in white blood cells and neutrophils. Her psychiatric symptoms improved, and she was discharged on Day 71. A blood test taken after discharge revealed that her white blood cell and neutrophil counts were within the normal range and she continued to take clozapine for 2 years. She has since been able to enjoy a calm and relaxed life at home. Conclusion: Exercise involving subjective and objective evaluation by an occupational therapist effectively increased white blood cells and neutrophils during clozapine treatment. Supervised exercise therapy by an occupational therapist is important when self-exercise is insufficient for continuing clozapine treatment. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0009-4536 2025 Elucidation of the relationship between solid‐state photoluminescence and crystal structures in 2,6‐substituted naphthalene derivatives EN Minoru Yamaji Department of Applied Chemistry, Division of Materials and Environment, Graduate School of Science and Engineering, Gunma University Isao Yoshikawa Department of Materials and Environmental Science, Institute of Industrial Science, The University of Tokyo Toshiki Mutai Technology Transfer Service Corporation Hirohiko Houjou Department of Materials and Environmental Science, Institute of Industrial Science, The University of Tokyo Kenta Goto Institute for Materials Chemistry and Engineering, Kyushu University Fumito Tani Institute for Materials Chemistry and Engineering, Kyushu University Kengo Suzuki Hamamatsu Photonics K.K Hideki Okamoto Department of Chemistry, Faculty of Environment, Life, Natural Sciences and Technology, Okayama University Polycyclic aromatic hydrocarbons (PAHs) are known to exhibit fluorescence in solution, but generally do not emit in the solid state, with the notable exception of anthracene. We previously reported that PAHs containing multiple chromophores show solid-state emission, and we have investigated the relationship between their crystal structures and photoluminescence properties. In particular, PAHs with herringbone-type crystal packing, such as 2,6-diphenylnaphthalene (DPhNp), which has a slender and elongated molecular structure, exhibits red-shifted solid-state fluorescence spectra relative to their solution-phase counterparts. In this study, we synthesized 2,6-naphthalene derivatives bearing phenyl and/or pyridyl substituents (PhPyNp and DPyNp) and observed distinct, red-shifted emission in the solid state compared with that in solution. Crystallographic analysis revealed that both PhPyNp and DPyNp adopt herringbone packing motifs. These findings support our hypothesis that the spectral characteristics of PAH emission are closely linked to crystal packing arrangements, providing a useful strategy for screening PAH candidates for applications in organic semiconducting materials. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1328-8067 67 1 2025 Changes in body mass index during early childhood on school‐age asthma prevalence classified by phenotypes and sex e70090 EN Toshihiko Yabuuchi Department of Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Masanori Ikeda Department of Pediatrics, Okayama University Medical School Naomi Matsumoto Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mitsuru Tsuge Department of Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Tsukahara Department of Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background: Few studies have explored the relationship between changes in body mass index(BMI) during early childhood and asthma prevalence divided by phenotypes and sex, and the limited results are conflicting. This study assessed the impact of BMI changes during early childhood on school-age asthma, classified by phenotypes and sex, using a nationwide longitudinal survey in Japan. Methods: From children born in 2001 (n = 47,015), we divided participants into BMI quartiles (Q1, Q2, Q3, and Q4) and the following BMI categories: Q1Q1 (i.e., Q1 at birth and Q1 at age 7), Q1Q4, Q4Q1, Q4Q4, and others. Asthma history from ages 7 to 8 was analyzed, with bronchial asthma (BA) further categorized as allergic asthma (AA) or nonallergic asthma (NA) based on the presence of other allergic diseases. Using logistic regression, we estimated the asthma odds ratio (OR) and 95% confidence intervals (CIs) for each BMI category. Results: Q1Q4 showed significantly higher risks of BA, AA, and NA. In boys, BA and NA risks were significantly higher in Q1Q4 (adjusted OR: 1.47 [95% CI: 1.17–1.85], at 1.56 [95% CI: 1.16–2.1]), with no significant difference in AA risk. In girls, no increased asthma risk was observed in Q1Q4, but AA risk was significantly higher in Q4Q4 (adjusted OR: 1.78 [95% CI: 1.21–2.6]). Conclusion: Our results demonstrated that BMI changes during early childhood impact asthma risks, particularly that the risk of NA in boys increases with BMI changes during early childhood, and the risk of AA in girls increases with consistently high BMI. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1613-6810 2025 Polyglycerol‐Grafted Graphene Oxide with pH‐Responsive Charge‐Convertible Surface to Dynamically Control the Nanobiointeractions for Enhanced in Vivo Tumor Internalization 2503029 EN Yajuan Zou Research Institute for Interdisciplinary Science, Okayama University Alberto Bianco Research Institute for Interdisciplinary Science, Okayama University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University pH-responsive charge-convertible nanomaterials (NMs) ameliorate the treatment of cancer via simultaneously reducing nonspecific interactions during systemic circulation and improving targeted uptake within solid tumors. While promising, little is known about how the pH-responsiveness of charge-convertible NMs directs their interactions with biological systems, leading to compromised performance, including off-target retention and low specificity to tumor cells. In the present study, polyglycerol-grafted graphene oxide bearing amino groups (GOPGNH2) at different densities are reacted with dimethylmaleic anhydride (DMMA), a pH-responsive moiety, to generate a set of charge-convertible GOPGNH-DMMA variants. This permits the assessment of a quantitative correlation between the structure of GOPGNH-DMMA to their pH-responsiveness, their dynamic interactions with proteins and cells, as well as their in vivo biological fate. Through a systematic investigation, it is revealed that GOPGNH115-DMMA prepared from GOPGNH2 with higher amine density experienced fast charge conversion at pH 7.4 to induce non-specific interactions at early stages, whereas GOPGNH60-DMMA and GOPGNH30-DMMA prepared from lower amine density retarded off-target charge conversion to enhance tumor accumulation. Notably, GOPGNH60-DMMA is also associated with enough amounts of proteins under acidic conditions to promote in vivo tumor internalization. The findings will inform the design of pH-responsive NMs for enhanced treatment accuracy and efficacy. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0815-9319 39 12 2024 Long‐term outcomes of endoscopic resection of superficial esophageal squamous cell carcinoma in late‐elderly patients 2664 2671 EN Katsunori Matsueda Department of Gastroenterology and Hepatology, Okayama University Hospital Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Hospital Keisuke Fukui Faculty of Societal Safety Sciences, Kansai University Shoichiro Hirata Department of Gastroenterology and Hepatology, Okayama University Hospital Takuya Satomi Department of Gastroenterology and Hepatology, Okayama University Hospital Shoko Inoo Department of Gastroenterology and Hepatology, Okayama University Hospital Kenta Hamada Department of Gastroenterology and Hepatology, Okayama University Hospital Yoshiyasu Kono Department of Gastroenterology and Hepatology, Okayama University Hospital Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Hospital Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Background and Aim: As the population ages, the number of elderly patients with superficial esophageal squamous cell carcinoma (ESCC) is increasing. We aimed to clarify the indications for endoscopic resection (ER) in late-elderly patients with ESCC in terms of life expectancy. Methods: Patients aged ≥75 years who underwent ER for ESCC at our institution from January 2005 to December 2018 were enrolled. Clinical data, including the Eastern Cooperative Oncology Group performance status, American Society of Anesthesiologists physical status (ASA-PS), Charlson comorbidity index, and prognostic nutritional index (PNI), were collected at the time of ER. The main outcome measure was overall survival (OS). Results: Two hundred eight consecutive patients were enrolled. The patients' median age was 78 years (range, 75–89 years). The 5-year follow-up rate was 88.5% (median follow-up period, 6.6 years). The 5-year OS rate was 79.2% (95% confidence interval [CI], 72.2–84.8), and 5-year net survival standardized for age, sex, and calendar year was 1.04 (95% CI, 0.98–1.09). In the multivariate analysis, an ASA-PS of 3 (hazard ratio, 2.45; 95% CI, 1.16–5.17) and PNI of <44.0 (hazard ratio, 2.73; 95% CI, 1.38–5.40) were independent prognostic factors. When neither of these factors was met, the 5-year OS rate was 87.8% (95% CI, 80.0–92.9), and 5-year net survival was 1.08 (95% CI, 1.02–1.14). Conclusions: ER for ESCC in late-elderly patients may improve life expectancy. ER is recommended in patients with a good ASA-PS and PNI. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2692-4609 4 1 2023 Alcohol consumption, multiple Lugol‐voiding lesions, and field cancerization e261 EN Chikatoshi Katada Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Tetsuji Yokoyama Department of Health and Promotion, National Institute of Public Health Tomonori Yano Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East Haruhisa Suzuki Endoscopy Division, National Cancer Center Hospital Yasuaki Furue Department of Gastroenterology, Kitasato University School of Medicine Keiko Yamamoto Division of Endoscopy, Hokkaido University Hospital Hisashi Doyama Department of Gastroenterology, Ishikawa Prefectural Central Hospital Tomoyuki Koike Division of Gastroenterology, Tohoku University Graduate School of Medicine Masashi Tamaoki Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Noboru Kawata Division of Endoscopy, Shizuoka Cancer Center Motohiro Hirao Department of Surgery, National Hospital Organization Osaka National Hospital Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Ogata Department of Gastroenterology, Kanagawa Cancer Center Atsushi Katagiri Department of Medicine, Division of Gastroenterology, Showa University Hospital Takenori Yamanouchi Department of Gastroenterology, Kumamoto Regional Medical Center Hirofumi Kiyokawa Division of Gastroenterology, Department of Internal Medicine, St. Marianna University School of Medicine Hirofumi Kawakubo Department of Surgery, Kawasaki Municipal Kawasaki Hospital Maki Konno Department of Gastroenterology, Tochigi Cancer Center Akira Yokoyama Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Shinya Ohashi Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Yuki Kondo Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Yo Kishimoto Department of Otolaryngology-Head and Neck Surgery, Kyoto University Hospital Koichi Kano Department of Otorhinolaryngology-Head and Neck Surgery, Kitasato University School of Medicine Kanae Mure Department of Public Health, Wakayama Medical University School of Medicine Ryuichi Hayashi Department of Head and Neck Surgery, National Cancer Center Hospital East Hideki Ishikawa Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine Akira Yokoyama Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center Manabu Muto Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University The development of multiple squamous cell carcinomas (SCC) in the upper aerodigestive tract, which includes the oral cavity, pharynx, larynx, and esophagus, is explained by field cancerization and is associated with alcohol consumption and cigarette smoking. We reviewed the association between alcohol consumption, multiple Lugol-voiding lesions, and field cancerization, mainly based on the Japan Esophageal Cohort study. The Japan Esophageal Cohort study is a prospective cohort study that enrolled patients with esophageal SCC after endoscopic resection. Enrolled patients received surveillance by gastrointestinal endoscopy every 6 months and surveillance by an otolaryngologist every 12 months. The Japan Esophageal Cohort study showed that esophageal SCC and head and neck SCC that developed after endoscopic resection for esophageal SCC were associated with genetic polymorphisms related to alcohol metabolism. They were also associated with Lugol-voiding lesions grade in the background esophageal mucosa, the score of the health risk appraisal model for predicting the risk of esophageal SCC, macrocytosis, and score on alcohol use disorders identification test. The standardized incidence ratio of head and neck SCC in patients with esophageal SCC after endoscopic resection was extremely high compared to the general population. Drinking and smoking cessation is strongly recommended to reduce the risk of metachronous esophageal SCC after treatment of esophageal SCC. Risk factors for field cancerization provide opportunities for early diagnosis and minimally invasive treatment. Lifestyle guidance of alcohol consumption and cigarette smoking for esophageal precancerous conditions, which are endoscopically visualized as multiple Lugol-voiding lesions, may play a pivotal role in decreasing the incidence and mortality of esophageal SCC. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0094-2405 52 8 2025 Commissioning of respiratory‐gated 4D dynamic dose calculations for various gating widths without spot timestamp in proton pencil beam scanning e18026 EN Yuki Tominaga Department of Radiotherapy, Medical Co. Hakuhokai, Osaka Proton Therapy Clinic Yushi Wakisaka Department of Radiotherapy, Medical Co. Hakuhokai, Osaka Proton Therapy Clinic Takahiro Kato Department of Radiological Sciences, School of Health Sciences, Fukushima Medical University Masaya Ichihara Medical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of Osaka Keisuke Yasui School of Medical Sciences, Fujita Health University Motoharu Sasaki Graduate School of Biomedical Sciences, Tokushima University Masataka Oita Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Teiji Nishio Medical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of Osaka Background: Proton pencil beam scanning (PBS) is susceptible to dose degradation because of interplay effects on moving targets. For cases of unacceptable motion, respiratory-gated (RG) irradiation is an effective alternative to free breathing (FB) irradiation. However, the introduction of RG irradiation with larger gate widths (GW) is hindered by interplay effects, which are analogous to those observed with FB irradiation. Accurate estimation of interplay effects can be performed by recording spot timestamps. However, our machine lacks this feature, making it imperative to find an alternative approach. Thus, we developed an RG 4-dimensional dynamic dose (RG-4DDD) system without spot timestamps. Purpose: This study aimed to investigate the accuracy of calculated doses from the RG-4DDD system for PBS plans with varying breathing curves, amplitudes, and periods for 10%–50% GW. Methods: RG-4DDDs were reconstructed using in-house developed software that assigned timestamps to individual spots, integrated start times for spills with breathing curves, and utilized deformable registrations for dose accumulation. Three cubic verification plans were created using a heterogeneous phantom. Additionally, typical liver and lung cases were employed for patient plan validation. Single- and multi-field-optimized (SFO and IMPT) plans (ten beams in total) were created for the liver and lung cases in a homogeneous phantom. Lateral profile measurements were obtained under both motion and no-motion conditions using a 2D ionization chamber array (2D-array) and EBT3 Gafchromic films on the CIRS dynamic platform. Breathing curves from the cubic plans were used to assess nine patterns of sine curves, with amplitudes of 5.0–10.0 mm (10.0–20.0 mm target motions) and periods of 3–6 sec. Patient field verifications were conducted using a representative patient curve with an average amplitude of 6.4 mm and period of 3.2 sec. Additional simulations were performed assuming a ± 10% change in assigned timestamps for the dose rate (DR), spot spill (0.08-s), and gate time delay (0.1-s) to evaluate the effect of parameter selection on our 4DDD models. The 4DDDs were compared with measured values using the 2D gamma index and absolute doses over that required for dosing 95% of the target. Results: The 2D-array measurements showed that average gamma scores for the reference (no motion) and 4DDD plans for all GWs were at least 99.9 ± 0.2% and 98.2 ± 2.4% at 3%/3 mm, respectively. The gamma scores of the 4DDDs in film measurements exceeded 95.4% and 92.9% at 2%/2 mm for the cubic and patient plans, respectively. The 4DDD calculations were acceptable under DR changes of ±10% and both spill and gate time delays of ±0.18 sec. For the 4DDD plan using all GWs for all measurement points, the absolute point differences for all validation plans were within ±5.0% for 99.1% of the points. Conclusions: The RG-4DDD calculations (less than 50% GW) of the heterogeneous and actual patient plans showed good agreement with measurements for various breathing curves in the amplitudes and periods described above. The proposed system allows us to evaluate actual RG irradiation without requiring the ability to record spot timestamps. 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. Methods: This post hoc analysis of a multicenter, retrospective, observational chart review, enrolling 370 patients with UC receiving VDZ between December 2018 and February 2020, compared effectiveness and safety of VDZ among patients ≥ 70 (n = 40) versus < 70 years (n = 330), and among patients ≥ 70 years with and without late-onset UC (age at disease onset: ≥ 70 [n = 13] versus < 70 years [n = 26]). Results: There were no differences between patients ≥ 70 and < 70 years in clinical remission rates (week 6: 57.5% vs. 47.6%, p = 0.9174; week 14: 62.5% vs. 54.8%, p = 0.1317; week 54: 47.5% vs. 46.4%, p = 0.8149), primary nonresponse (10.0% vs. 15.5%, p = 0.6248), loss of response (12.5% vs. 9.4%, p = 0.5675), or overall safety. Among patients ≥ 70 years, the incidence of adverse drug reactions was numerically greater in those with concomitant corticosteroids than in those without. For older patients with and without late-onset UC, week 54 remission rates were 23.1% versus 57.7% (p = 0.0544); surgery was reported in 3/13 versus 2/26 patients and hospitalization in 5/13 versus 6/26 patients. One death was reported in patients with late-onset UC. Conclusions: VDZ effectiveness and safety were similar in patients ≥ 70 and < 70 years; VDZ may be a suitable treatment option for patients ≥ 70 years with UC. Patients with late-onset UC tended to have more frequent surgery/hospitalization and lower effectiveness than those without, possibly necessitating greater caution when using VDZ. Trial Registration: Japanese Registry of Clinical Trials registration number: jRCT-1080225363 No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2197-1153 12 2 2025 Progression of patellofemoral joint cartilage degeneration within 1 year after medial meniscus posterior root repair: A retrospective study e70139 EN Masanori Tamura Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takayuki Furumatsu Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital 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 Koki Kawada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tsubasa Hasegawa 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 Purpose: To assess postoperative progression of patellofemoral (PF) cartilage degeneration after medial meniscus posterior root (MMPR) repair and identify potential risk factors. Methods: Data from patients who underwent transtibial pullout repair for complete radial MMPR tears between April 2018 and October 2021 were retrospectively investigated. Patients with severe chondral lesions of the PF joint at primary surgery were excluded. All patients underwent second-look arthroscopy at 12 months postoperatively. Postoperative changes using the International Cartilage Repair Society (ICRS) grade were evaluated. Associated open magnetic resonance imaging (MRI) findings were assessed. Results: In total, 40 patients (30 women, 10 men; mean age: 64.0 years) were evaluated. PF joint cartilage degeneration progressed significantly postoperatively. Abnormal signal intensity (ASI) of the infrapatellar fat pad (IPFP) was observed in 15 (37.5%) patients. Arthroscopic findings in groups between IPFP with and without ASI were compared. The incidence of postoperative ICRS grade worsening (≥2 grades) on the patella or trochlea was significantly higher among patients with ASI (53%) than among those without (20%, p = 0.04). ICRS grade worsening in the medial femorotibial compartment and meniscus-healing status were comparable between the groups. Patients with ASI of the IPFP showed greater decrease in the distance between the patellar and anterior cruciate ligament insertions on knee flexion MRI (−1.5 ± 0.7 mm) than that in those without (−0.2 ± 0.3 mm, p < 0.01). A delayed rehabilitation protocol was a risk factor according to the logistic regression analysis (p = 0.01). Conclusions: Progressive PF cartilage degeneration occurred following MMPR repair, highlighting the need for diligent postoperative PF joint management. Level of Evidence: Level IV case series. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2197-1153 12 2 2025 Occupational motions such as kneeling and squatting are associated with the increased development of medial meniscus posterior root tears, regardless of the medial posterior tibial slope angle e70276 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 Masanori Tamura 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 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 Purpose: The relationship between occupational motions and the medial posterior tibial slope (MPTS) with the development of medial meniscus posterior root tears (MMPRTs) has not been investigated. The development of non-traumatic degenerative MMPRTs may be influenced by repetitive occupational motions and bone morphological characteristics. Herein, we examined the association between occupational motions and MPTS in patients with MMPRT development. Methods: During the first medical examination, MPTS was measured using lateral knee radiographic images, and occupational motions were investigated in 559 patients (591 knees). Occupational motions were classified as kneeling and squatting, standing and walking, sitting, lifting heavy weights, and housework. Mann–Whitney U test was used to compare patient characteristics between male and female patients and MPTS relative to occupational motion. Results: The most frequent occupational motion was housework (160/559 patients, 28.6%), followed by kneeling and squatting (140/559, 25.0%), standing and walking (128/559, 22.9%), sitting (82/559, 14.7%), and lifting heavy weights (49/559, 8.8%). Furthermore, housework (10.0 ± 2.6°) involved significantly greater MPTS than kneeling and squatting (9.3 ± 2.7°; p = 0.012). However, the MPTS associated with other occupational motions was not significantly different from that associated with housework. Conclusion: The most frequent occupational motion among patients with MMPRTs was housework, followed by kneeling and squatting. Patients who performed housework tended to have a higher MPTS. Occupational motions such as kneeling and squatting potentially increase the development of MMPRTs, even without a high MPTS. Level of Evidence: Level IV. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2197-1153 11 4 2024 Quadriceps muscle strength of the affected limb in medial meniscus posterior root tears is negatively correlated with the progression of postoperative medial joint space narrowing e70057 EN Koki Kawada Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Mikao Fukuba Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yuki Okazaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Masanori Tamura Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yusuke Yokoyama Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takayuki Furumatsu Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Purpose: The effect of quadriceps muscle strength on medial joint space (MJS) narrowing after repair for medial meniscus (MM) posterior root tears (MMPRTs) has not yet been determined. This study aimed to evaluate the effect of preoperative and postoperative quadriceps muscle strength on the change in MJS (ΔMJS) in MMPRTs. Methods: Thirty patients who underwent pullout repair for MMPRTs were retrospectively evaluated. The MJS width using fixed-flexion view radiographs, MM extrusion (MME) using magnetic resonance imaging, quadriceps muscle strength using the Locomo Scan-II and clinical scores were measured and compared preoperatively and 1 year postoperatively. Correlations between the ΔMJS, change in MME (ΔMME), and preoperative and postoperative quadriceps muscle strength were evaluated using Spearman's rank correlation coefficient. Results: MJS narrowing and MME progressed significantly at 1 year postoperatively (p < 0.001). Quadriceps muscle strength in MMPRT knees and all clinical scores significantly improved at 1 year postoperatively (p < 0.001). ΔMJS and ΔMME showed a significant positive correlation (0.50 ± 0.70 and 1.22 ± 0.92 mm, respectively; r = 0.516, p = 0.004). Both preoperative and postoperative quadriceps muscle strength in MMPRT knees showed significant negative correlations with ΔMJS (preoperative: r = −0.529, p = 0.003; postoperative: r = −0.477, p = 0.008) and ΔMME (preoperative: r = −0.431, p = 0.018; postoperative: r = −0.443, p = 0.014). Conclusions: In pullout repair for MMPRTs, preoperative and postoperative quadriceps muscle strength in MMPRT knees was negatively correlated with the progression of MJS narrowing and MME. Rehabilitation with a focus on quadriceps muscle strengthening, including preoperative rehabilitation, may delay knee-osteoarthritis progression after pullout repair for MMPRTs. Level of Evidence: Level IV. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1351-5101 32 1 2025 Lyme neuroborreliosis in Japan: Borrelia burgdorferi sensu lato as a cause of meningitis of previously undetermined etiology in hospitalized patients outside of the island of Hokkaido, 2010–2021 e70005 EN Masayuki Ohira Department of Clinical Laboratory and Internal Medicine, National Center of Neurology and Psychiatry Ai Takano Department of Veterinary Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University Kentaro Yoshi National Research Center for the Control and Prevention of Infectious Diseases, Nagasaki University Akira Arai Department of Neurology, Aomori Prefectural Central Hospital Yashuhiro Aso Department of Neurology, Oita Prefectural Hospital Rikiya Furutani Department of Neurology, National Hospital Organization, Shinshu Ueda General Hospital Tadanori Hamano Department of Neurology, University of Fukui Hospital Ikuko Takahashi‐Iwata Department of Neurology, Hokkaido University Hospital Chikako Kaneko Department of Neurology, Southern Tohoku General Hospital Tohru Matsuura Division of Neurology, Jichi Medical University Norihisa Maeda Department of Neurology, National Hospital Organization Beppu Medical Center Hideto Nakajima Department of Neurology, Nihon University Itabashi Hospital Katsuro Shindo Department of Neurology, Kurashiki Central Hospital Toshihiko Suenaga Department of Neurology, Tenri Hospital Kazuma Sugie Department of Neurology, Nara Medical University Hospital Yasuhiro Suzuki Department of Neurology, National Hospital Organization Asahikawa Medical Center Toru Yamashita Department of Neurology, Okayama University Hospital Frederick J. Angulo Vaccines and Antivirals Medical Affairs, Pfizer Vaccines Juanita Edwards Vaccines and Antivirals Medical Affairs, Pfizer Vaccines Cody Matthew Bender Vaccines and Antivirals Medical Affairs, Pfizer Vaccines Lisa R. Harper Vaccines and Antivirals Medical Affairs, Pfizer Vaccines Yoshikazu Nakayama Vaccines Medical Affairs, Pfizer Japan Inc Shuhei Ito Vaccines Medical Affairs, Pfizer Japan Inc Andreas Pilz Vaccines and Antivirals Medical Affairs, Pfizer Vaccines James H. Stark Vaccines and Antivirals Medical Affairs, Pfizer Vaccines Jennifer C. Moïsi Vaccines and Antivirals Medical Affairs, Pfizer Vaccines Hidehiro Mizusawa Department of Neurology, National Center of Neurology and Psychiatry Masaki Takao Department of Clinical Laboratory and Internal Medicine, National Center of Neurology and Psychiatry Background and Purpose: Clinical manifestations of Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl), include erythema migrans, Lyme neuroborreliosis (LNB), carditis, and arthritis. LB is a notifiable disease in Japan with <30 surveillance-reported LB cases annually, predominately from Hokkaido Prefecture. However, LB, including LNB, may be under-diagnosed in Japan since diagnostic tests are not readily available. We sought to determine if LNB could be a cause of previously undiagnosed encephalitis or meningitis in Japan. Methods: Investigators at 15 hospitals in 10 prefectures throughout Japan retrieved serum and/or cerebrospinal fluid (CSF) samples collected in 2010–2021 from 517 patients hospitalized with encephalitis or meningitis which had an etiology that had not been determined. Samples were tested for Bbsl-specific antibodies using ELISA and Western blot tests. In alignment with the European Union LNB case definition, a confirmed LNB case had CSF pleocytosis and intrathecal production of Bbsl-specific antibodies and a probable LNB case had a CSF sample with pleocytosis and Bbsl-specific antibodies. Results: LNB was identified in three hospitalized patients with meningitis of previously undetermined etiology: a male resident of Aomori Prefecture was a confirmed LNB case, and two female residents of Oita Prefecture were probable LNB cases. None of the patients with confirmed or probable LNB had traveled in the month prior to symptom onset and none had samples previously tested for LB. Conclusion: The identification of previously undiagnosed LNB cases indicates a need for enhanced disease awareness in Japan, particularly beyond Hokkaido Island, and more readily available LB diagnostic testing. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0020-7292 2025 Determinants of residual myometrial thickness after cesarean delivery: Comparative analysis of barbed versus conventional sutures—A sub‐analysis from the SPIRAL trial EN Jota Maki Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hikaru Ooba Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Mitoma Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hikari Nakato Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayano Suemori Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiaki Kuriyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shujiro Sakata Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sakurako Mishima Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Ohira Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eriko Eto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objective: This sub-analysis aimed to determine whether conventional suture-associated risk factors for cesarean scar defect show similar outcomes with barbed continuous suturing, and to identify factors influencing residual myometrial thickness when using barbed continuous sutures. Methods: This sub-analysis of a multicenter, parallel-group, randomized controlled trial across four Japanese obstetrics and gynecology departments included 1211 women who had their first cesarean delivery between May 2020 and March 2023. Among them, 298 women underwent a C-section, with 253 follow-up through July 2023. Singleton pregnancies were randomly assigned to receive either barbed or conventional double-layered continuous sutures in a 1:1 ratio; they were monitored from consent through their 6- to 7-month check-up. The effects of cervical ripening, facility characteristics, and surgeon experience were investigated using a two-way ANOVA. Results: Of the remaining 253 patients, 33 were lost to follow-up and 220 completed follow-up (110 per group). One institution enrolled the largest proportion of participants (45.9%), whereas two other institutions had more experienced surgeons. Two-way ANOVA revealed that surgeon experience (P = 0.020) and institutional factors (P < 0.001) significantly influenced the residual myometrial thickness at 6–7 months after surgery, whereas cervical dilation during active labor did not (P = 0.215). Additionally, a significant interaction was observed between institutional factors and suture type (barbed vs. conventional) on residual myometrial thickness (Pinteraction <0.001). Conclusion: Institutional factors and surgeon experience represent significant determinants of residual myometrial thickness when using barbed sutures for cesarean closure, highlighting the importance of standardized surgical protocols and training across facilities. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 13 7 2025 Tongue Schwannoma at the Median Inferior Surface in the Elderly: A Case Report e70506 EN Kiho Fukushima Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kisho Ono Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kyoichi Obata Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Izumi Yamamoto Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Kunisada Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Yutori Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University We report the extremely rare case of an atypical schwannoma that occurred at the median inferior surface of the tongue in an elderly patient. We performed an excisional biopsy to achieve a definitive diagnosis. Based on the histopathological findings, we diagnosed a schwannoma (mixed type, Antoni A/B). 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. Patients and Methods: In this study, three types of DNA panel and one DNA–RNA panel, reimbursed by Japanese public health insurance, were utilized. We detected oncogenic and druggable gene mutations and genotype-matched therapies. Results: One hundred and thirty-six patients were included in this study. Based on the detection of highly histology-specific translocations in the sequencing results, 2.2% of patients were re-classified. In patients with translocation-related sarcomas, a DNA–RNA panel identified more histology-specific fusion genes than DNA panels (p = 0.0035). Specifically, 86.8% and 39.0% of patients had oncogenic and druggable genomic alterations, respectively. Of these, 9.6% underwent genotype-matched therapy, with a 36.3% response rate and an 81.8% disease control rate. Patients who were administered genomically matched therapy had better overall survival (OS) than those who did not in patients with metastatic or advanced sarcoma with no prior chemotherapy (3-year OS: 83.3% vs. 48.0%, p = 0.42). Patients with TP53 and RB1 mutations had worse OS than those without. Germline findings were detected in 11.0% of the patients, one of whom had a truly germline origin. Conclusions: This study suggests that publicly reimbursed CGP tests, particularly the dual DNA–RNA panel, could be beneficial for refining diagnostic precision in selected sarcoma subtypes, treatment decisions, detecting the germline findings, and prognosis prediction in routine clinical settings for sarcoma. The implementation of genotype-matched therapies showed favorable clinical outcomes and improved the prognosis. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2475-0328 8 6 2024 High risk of multiple gastric cancers in Japanese individuals with Lynch syndrome 1008 1016 EN Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Thijs A. van Schaik Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School Hideki Aoki Department of Surgery, National Hospital Organization Iwakuni Clinical Center Yumiko Sato Department of Pathology, National Hospital Organization Iwakuni Clinical Center Fumitaka Taniguchi Department of Surgery, National Hospital Organization Iwakuni Clinical Center Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kokichi Sugano Department of Genetic Medicine, Kyoundo Hospital, SSasaki Foundation Kiwamu Akagi Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center Hideyuki Ishida Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University Kohji Tanakaya Department of Surgery, National Hospital Organization Iwakuni Clinical Center Aim: Lynch syndrome (LS) is a dominantly inherited syndrome characterized by an increased risk for LS associated tumors such as colorectal cancer (CRC) and gastric cancer (GC). However, the clinical benefit of surveillance for GC remains unclear while it has already been recommended for CRC. This study aimed to elucidate the clinical features of GC in Japanese individuals with LS, and the risk of developing multiple GCs to build regional-tailored surveillance programs in LS patients with GC. Methods: Data on Japanese individuals with LS were retrospectively collected from a single institution. The clinical features of GC, including the cumulative risk of multiple GCs, were analyzed. Results: Among 96 individuals with LS (MLH1/MSH2/MSH6, 75:20:1), 32 GC lesions were detected in 15 individuals with LS (male/female, 11:4). The median age at initial GC diagnosis was 52.7 y (range: 28–71). Histological examination revealed a predominance of intestinal type (19/24: 87.5%). Moreover, the majority of the GC lesions (82%) were determined to have high-frequency of microsatellite instability. The cumulative risk of individuals with LS developing GC at 70 y was 31.3% (MLH1 36.1%, MSH2 18.0%). Notably, the cumulative risk of individuals with LS developing metachronous and/or synchronous GCs at 0, 10 and 20 y after initial diagnosis of GC was 26.7%, 40.7%, and 59.4%, respectively. Conclusion: Due to a higher risk of developing multiple GCs, intensive surveillance might be especially recommended for Japanese individuals with LS associated initial GC. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 12 5 2024 The Japan MSA registry: A multicenter cohort study of multiple system atrophy 271 277 EN Ayaka Chikada Department of Neurology, Graduate School of Medicine, The University of Tokyo Kenta Orimo Department of Neurology, Graduate School of Medicine, The University of Tokyo Jun Mitsui Department of Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine and Dentistry Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Hidehiro Mizusawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Yuji Takahashi Department of Neurology, Graduate School of Medicine, The University of Tokyo Masahisa Katsuno Department of Neurology, Nagoya University Graduate School of Medicine Kazuhiro Hara Department of Neurology, Nagoya University Graduate School of Medicine Osamu Onodera Department of Neurology, Brain Research Institute, Niigata University Tomohiko Ishihara Department of Neurology, Brain Research Institute, Niigata University Masayoshi Tada Department of Neurology, Brain Research Institute, Niigata University Satoshi Kuwabara Department of Neurology, Graduate School of Medicine, Chiba University Atsuhiko Sugiyama Department of Neurology, Graduate School of Medicine, Chiba University Yoshitaka Yamanaka Department of Neurology, Graduate School of Medicine, Chiba University Ryosuke Takahashi Department of Neurology, Kyoto University Graduate School of Medicine Nobukatsu Sawamoto Department of Human Health Sciences, Kyoto University Graduate School of Medicine Yusuke Sakato Department of Neurology, Kyoto University Graduate School of Medicine Tomoyuki Ishimoto Department of Neurology, Kyoto University Graduate School of Medicine Ritsuko Hanajima Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University Yasuhiro Watanabe Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University Hiroshi Takigawa Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University Tadashi Adachi Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University Koji Abe Department of Neurology, Okayama University Graduate School of Medicine and Dentistry Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine and Dentistry Hiroshi Takashima Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University Keiko Higashi Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University Junichi Kira Department of Neurology, Graduate School of Medical Sciences, Kyushu University Ichiro Yabe Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Masaaki Matsushima Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Katsuhisa Ogata Department of Neurology, Higashi-Saitama National Hospital Kinya Ishikawa Department of Neurology and Neurological Science, Tokyo Medical and Dental University Yoichiro Nishida Department of Neurology and Neurological Science, Tokyo Medical and Dental University Taro Ishiguro Department of Neurology and Neurological Science, Tokyo Medical and Dental University Kokoro Ozaki Department of Neurology and Neurological Science, Tokyo Medical and Dental University Tetsuya Nagata Department of Neurology and Neurological Science, Tokyo Medical and Dental University Shoji Tsuji Department of Neurology, Graduate School of Medicine, The University of Tokyo Background: Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure and various motor symptoms. While MSA-C (cerebellar type) predominates in East Asia, MSA-P (parkinsonian type) predominates in Europe and North America. This nationwide patient registry aimed to (1) conduct a prospective natural history study of MSA in Japan, (2) facilitate patient recruitment for clinical trials, and (3) deposit bioresources and clinical information in a biobank. Methods: Thirteen institutions participated in this study. Clinical information was obtained by neurologists from the patients visiting the hospital every 12 months to assess the UMSARS Part 2 scores and by telephone interviews by nurses every 6 months to assess UMSARS Part 1 scores and to determine whether clinical events had occurred. Results: Demographic data from 329 MSA patients (216 MSA-C and 113 MSA-P) were analyzed. The mean age at symptom onset was 58.2 years (standard deviation, 8.9); the mean duration of symptoms at enrollment was 3.5 years (standard deviation, 2.2). The mean 12-month changes in the UMSARS Part 1 and Part 2 scores were 7.9 (standard deviation, 5.6) and 6.4 (standard deviation, 5.9), respectively. The patient registry proved useful in recruiting participants for clinical trials, including those with gene variants. Clinical information and biospecimens were deposited in a biobank. Discussion: The study highlighted the importance of telephone interviews in minimizing drop-out rates in natural history studies and demonstrated similar MSA progression rates across populations. The deposited bioresources are available to researchers upon request, aiming to contribute to future MSA researches. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 13 2 2024 A novel de novo disease-causing variant in ATL1 in a pediatric patient with spastic paraplegia 159 161 EN Ayumi Nakamura Department of Neurology, Graduate School of Medicine, The University of Tokyo Hiroya Naruse Department of Neurology, Graduate School of Medicine, The University of Tokyo Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo Jun Mitsui Department of Neurology, Graduate School of Medicine, The University of Tokyo Shinichi Morishita Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo Mie Iwakoshi Department of Nursing, Faculty of Health Sciences, Kobe Tokiwa University Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoji Tsuji Institute of Medical Genomics, International University of Health and Welfare Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1880-4276 41 4 2025 Prevalence, Characteristics, and Arrhythmogenic Substrate of Mitral Annular Disjunction Assessed by Cardiac Magnetic Resonance Imaging in Patients With Apparently Idiopathic Ventricular Arrhythmia e70172 EN Saori Asada Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihisa Toh Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Takuro Masuda Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Akira Ueoka Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Masakazu Miyamoto Department of Cardiology, Kagawa Prefectural Central Hospital Koji Nakagawa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Nobuhiro Nishii Kazufumi Nakamura Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Shinsuke Yuasa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Background: Mitral annular disjunction (MAD) is linked to an increased risk of sudden cardiac death, but its association with ventricular arrhythmias (VAs) in Japanese patients is unclear. Methods: We retrospectively analyzed 129 Japanese patients with VAs and no overt structural heart disease who underwent echocardiography and cardiac MRI. Results: MAD was diagnosed in 7.0%, and in 14% of patients with VAs originating from the mitral valve apparatus. MAD was significantly associated with multifocal VAs, late gadolinium enhancement in the papillary muscles, and greater mitral regurgitation. Conclusion: MAD may be an important arrhythmogenic substrate in apparently idiopathic VAs among Japanese patients. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2197-1153 12 2 2025 Clinical outcomes following medial meniscus posterior root repairs: A minimum of 5‐year follow‐up study e70262 EN Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhisa Sugiu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yusuke Kamatsuki Department of Orthopaedic Surgery, Okayama Saiseikai General Hospital Masanori Tamura Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Koki Kawada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tsubasa Hasegawa 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 Purpose: This study assessed the clinical outcomes of the FasT-Fix dependent modified Mason-Allen suture (F-MMA) and two simple stitches (TSS) on mid-term postoperative outcomes following medial meniscus (MM) posterior root repair. Methods: Forty-three patients who underwent transtibial pullout repair for MM posterior root tear (PRT) between November 2016 and September 2018 were initially enrolled. Patients with a femorotibial angle ≤ 180°, Kellgren–Lawrence grade of 0–2, and modified Outerbridge grade I or II cartilage lesions were included. The Lysholm, Tegner activity, International Knee Documentation Committee score, pain visual analogue scale and Knee injury and Osteoarthritis Outcome scores were assessed as clinical outcomes. Conversion surgery to knee arthroplasty was considered as the endpoint. Surgeries other than second-look arthroscopy and plate or screw removal were also recorded. Results: The mean follow-up period was 5.9 years. All evaluated 5-year postoperative clinical outcomes were significantly improved compared to the preoperative outcomes (p < 0.001). Both the F-MMA and TSS significantly improved all clinical scores at 5 years postoperatively in patients with MMPRT, whereas the F-MMA and TSS groups showed no significant differences in the pre- and postoperative clinical scores. None of the patients required ipsilateral knee arthroplasty during the follow-up, and the survival rate after pullout repair was 100%. However, the progression of osteoarthritis could not be completely suppressed, although there were no Kellgren–Lawrence grade 4 cases. The rate of subsequent knee-related surgical treatment was 11.6% in pullout-repaired knees, including arthroscopic debridement for arthrofibrosis with a limited range of motion, an additional all-inside suture repair and partial meniscectomy. Conclusion: Both F-MMA and TSS pullout repairs yielded satisfactory clinical outcomes in patients with MMPRT with a mean follow-up of 5.9 years, and no conversion to knee arthroplasty was required. Further follow-up is warranted to assess long-term survival rates. Level of Evidence: Level III. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2040-1116 2025 Relationship between maternal body composition changes and heavy for date infants in pregnant women with diabetes EN Eriko Eto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masakazu Kato Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoe Kirino Chiaki Kuriyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Syujiro Sakata Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hikari Nakato Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sakurako Mishima Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Ohira Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aims/Introduction: Maternal hyperglycemia is associated with heavy for date (HFD) infants. Considering the association between body composition and hyperglycemia, we investigated the changes in maternal body composition and their relationship with HFD infants in pregnant women with diabetes. Materials and Methods: Body composition was measured during pregnancy using a bioelectrical impedance analysis system. This retrospective study included 151 pregnant women; 27 women had type 1 diabetes mellitus (DM), 21 had type 2 DM, 101 were diagnosed with gestational DM, and 2 had overt DM. The number of HFD infants was 40. Results: In the non-type 1 DM group, change in fat mass (ΔFM) (P < 0.01) and pre-pregnancy BMI (P < 0.05) were risk factors for HFD. In the insulin group, ΔFM, pre-pregnancy BMI, and age (all P < 0.05) were risk factors for HFD. The area under the curve was 0.813 for the predictive model combined with ΔFM and pre-pregnancy BMI in the non-type 1 DM group and 0.818 for the model combined with ΔFM, pre-pregnancy BMI, and age in the insulin group. Conclusions: The combination of body composition parameters and clinical data may predict HFD in pregnant women with diabetes. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1613-6810 2025 Droplet Transportation on Janus Harp Wires for Enhanced Fog Harvesting e06765 EN Yutaka Yamada Faculty of Environmental, Life, Natural Science and Technology, Okayama University Taku Ishikawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuma Isobe Faculty of Environmental, Life, Natural Science and Technology, Okayama University Akihiko Horibe Faculty of Environmental, Life, Natural Science and Technology, Okayama University Ensuring freshwater resources is a vital issue for human beings worldwide. Fog harvesting is one promising way to provide water from unconventional sources. However, clogging by the captured liquid depresses the fog harvesting performance. Here, a harp-shaped Janus harvesting system, which has thin wires with a superhydrophobic side facing the fog stream and a superhydrophilic back side to transport the droplets, is used to yield simultaneous fog capturing and water transport abilities. Attached droplets on the Janus wire transported along the periphery avoided clogging and enhanced the performance. The Janus system thus suppressed the increase and fluctuations of actual shade coefficients, which indicated blockage of the fog stream. This optimized the design of the harvester. Experiments using a multilayered Janus harvester demonstrated a significant enhancement compared with that constructed with mono-wettability wires. Overall, the results indicated the promise of droplet transportation on single wires for improving fog harvesting, as well as for other applications such as oil mist recovery and demulsification. 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. 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. 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. 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.

Wiley Acta Medica Okayama 2642-4150 2025 Electrostatically‐Driven Collapse of Polyelectrolytes: The Role of the Solvent's Dielectric Constant EN Anish Gulati Institute of Physical Chemistry, RWTH Aachen University Lingzi Meng Materials Science and Engineering Department, The Pennsylvania State University, State College Takaichi Watanabe Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Carlos G. Lopez Materials Science and Engineering Department, The Pennsylvania State University, State College We experimentally confirm a longstanding theoretical prediction of counterion-induced polyelectrolyte collapse in low dielectric media. The scattering behavior of polystyrene sulfonate in different solvents with dielectric permittivities in the range of ε ≃ 12 − 180 is investigated. For high and intermediate ε media, typical polyelectrolyte behavior is observed: the correlation length (ξ) scales with concentration (c) as ξ ∼ c−1∕2, as predicted by various theories. When the dielectric constant of the solvent decreases below ≃ 22, a scaling of ξ ∼ c−1∕3, characteristic of partially collapsed polyelectrolytes, is observed. For these solvents, the correlation peak disappears at high concentrations. Interestingly, polyelectrolyte collapse is observed under both solvophilic and solvophobic conditions, supporting the existence of attractive electrostatic interactions. These results are in qualitative agreement with theoretical predictions which expect chain collapse in low dielectric media due to the influence of condensed counterions, either via dipolar attraction and/or charge-correlation-induced attractions. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0952-3480 38 9 2025 Ultrahigh‐Field MR‐Compatible Mechanical Tactile Stimulator for Investigating Somatosensory Processing in Small‐Bodied Animals e70105 EN Chenyu Wang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Hirohiko Imai Innovation Research Center for Quantum Medicine, Gifu University School of Medicine Masaki Fukunaga Section of Brain Function Information, National Institute for Physiological Sciences Hiroki Yamamoto Graduate School of Human and Environmental Studies, Kyoto University Yinghua Yu Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kazuhiko Seki Department of Neurophysiology, National Center of Neurology and Psychiatry Takashi Hanakawa Department of Integrated Neuroanatomy and Neuroimaging, Kyoto University Graduate School of Medicine Tatsuya Umeda Department of Integrated Neuroanatomy and Neuroimaging, Kyoto University Graduate School of Medicine Jiajia Yang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Common marmosets (Callithrix jacchus), small-bodied New World primates that share similar sensory processing pathways with human beings, have gained great interests. Their small body size allows imaging of brain activity with high spatial resolution and on a whole-brain scale using ultrahigh-field (UHF) magnetic resonance imaging (MRI) scanners. However, the strong magnetic field and the small size of the hand and forearm pose challenges in delivering tactile stimulation during fMRI experiments. In the present study, we developed an MR-compatible tactile dual-point stimulator to provide high-precision mechanical stimulation for exploring somatosensory processing in small-bodied animals. The study population consisted of a water phantom and three male common marmosets. Cerebral blood volume (CBV) weighted fMRI data were obtained with a gradient echo (GE), echo-planar imaging (EPI) sequence at 7T scanner. The output performance of the device was tested by a pressure sensor. The MR compatibility of the device was verified by measuring the temporal signal-to-noise ratio (tSNR) of a water phantom. To test the effectiveness of tactile stimulation, we conducted block designed tactile stimulation experiments on marmosets. A one-way repeated measures ANOVA was conducted for comparing the tSNR results. We performed one-sample t-tests to investigate the negative response of the forearm and hand stimulation with a threshold of t > 1.96 (p < 0.05). Performance tests revealed that mechanical stimulation (averaged force: 31.69 g) was applied with a delay of 12 ms. Phantom experiments confirmed that there was no significant difference in the tSNR among three (10 Hz, 1 Hz, and no-stimulus) conditions (F (2, 798) = 0.71, p = 0.49). The CBV activity results showed that the stimulator successfully elicited hand and forearm somatosensory activations in primary somatosensory areas. These results indicated that the device is well suited for small-bodied animal somatosensory studies. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2692-4609 6 1 2025 A Case of Gastric Atypical Lipomatous Tumor/Well‐Differentiated Liposarcoma With Endoscopic Morphological Changes e70146 EN Rika Omote Department of Diagnostic Pathology, NHO Fukuyama Medical Center Shizuma Omote Department of Internal Medicine, Fukuyama Minami Hospital Hiroshi Sonobe Department of Diagnostic Pathology, NHO Fukuyama Medical Center Ryosuke Hamano Department of Surgery, NHO Fukuyama Medical Center Tatsuya Toyokawa Department of Gastroenterology, NHO Fukuyama Medical Center Shinya Otsuka Department of Surgery, NHO Fukuyama Medical Center Takehiro Tanaka Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Yanai Department of Pathology, Okayama University Hospital Masaru Inagaki Department of Surgery, NHO Fukuyama Medical Center Hidetaka Yamamoto Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atypical lipomatous tumor/well-differentiated liposarcoma is a locally aggressive mesenchymal neoplasm composed of adipocytes and stromal cells. Gastric cases are exceedingly rare, and their malignant potential remains unclear. We report a case of a woman in her 60s who was found to have multiple submucosal tumor-like lesions of the stomach. Over time, the tumors increased in size, requiring a laparoscopic partial gastrectomy. Histological examination revealed a tumor composed of both fatty tissue and fibrous stroma with nuclear atypia. Immunohistochemistry showed positivity for CDK4 and MDM2, and fluorescence in situ hybridization confirmed MDM2 amplification, leading to a diagnosis of atypical lipomatous tumor/well-differentiated liposarcoma. This case presented an unusual gastric manifestation, with multiple submucosal tumor-like lesions on endoscopy and exhibiting progressive morphological changes over several years. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1388-9842 2025 Employment of artificial intelligence for an unbiased evaluation regarding the recovery of right ventricular function after mitral valve transcatheter edge-to-edge repair EN Vera Fortmeier Department of General and Interventional Cardiology, Heart and Diabetes Center Northrhine-Westfalia, Ruhr University Bochum Amelie Hesse Department of Internal Medicine I, Klinikum rechts der Isar, TUM University Hospital, School of Medicine and Health, Technical University of Munich Teresa Trenkwalder DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance Márton Tokodi Heart and Vascular Center, Semmelweis University Attila Kovács Heart and Vascular Center, Semmelweis University Elena Rippen Department of Internal Medicine I, Klinikum rechts der Isar, TUM University Hospital, School of Medicine and Health, Technical University of Munich Jule Tervooren Department of Internal Medicine I, Klinikum rechts der Isar, TUM University Hospital, School of Medicine and Health, Technical University of Munich Michelle Fett Department of General and Interventional Cardiology, Heart and Diabetes Center Northrhine-Westfalia, Ruhr University Bochum Gerhard Harmsen Department of Physics, University of Johannesburg Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Moritz Kühlein Department of Cardiovascular Diseases, German Heart Center Munich, School of Medicine and Health, TUM University Hospital, Technical University of Munich Héctor Alfonso Alvarez Covarrubias Department of Cardiovascular Diseases, German Heart Center Munich, School of Medicine and Health, TUM University Hospital, Technical University of Munich Moritz von Scheidt DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance Ferdinand Roski Department of Cardiovascular Diseases, German Heart Center Munich, School of Medicine and Health, TUM University Hospital, Technical University of Munich Muhammed Gerçek Department of General and Interventional Cardiology, Heart and Diabetes Center Northrhine-Westfalia, Ruhr University Bochum Tibor Schuster Department of Family Medicine, McGill University N. Patrick Mayr Institute of Anesthesiology, German Heart Center Munich, School of Medicine and Health, TUM University Hospital, Technical University of Munich Erion Xhepa DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance Karl‐Ludwig Laugwitz Department of Internal Medicine I, Klinikum rechts der Isar, TUM University Hospital, School of Medicine and Health, Technical University of Munich Michael Joner DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance Volker Rudolph Department of General and Interventional Cardiology, Heart and Diabetes Center Northrhine-Westfalia, Ruhr University Bochum Mark Lachmann Department of Internal Medicine I, Klinikum rechts der Isar, TUM University Hospital, School of Medicine and Health, Technical University of Munich Aims Long-standing severe mitral regurgitation (MR) leads to left atrial (LA) enlargement, elevated pulmonary artery pressures, and ultimately right heart failure. While mitral valve transcatheter edge-to-edge repair (M-TEER) alleviates left-sided volume overload, its impact on right ventricular (RV) recovery is unclear. This study aims to use both conventional echocardiography and artificial intelligence to assess the recovery of RV function in patients undergoing M-TEER for severe MR. Methods and results The change in RV function from baseline to 3-month follow-up was analysed in a dual-centre registry of patients undergoing M-TEER for severe MR. RV function was conventionally assessed by measuring the tricuspid annular plane systolic excursion (TAPSE). Additionally, RV function was evaluated using a deep learning model that predicts RV ejection fraction (RVEF) based on two-dimensional apical four-chamber view echocardiographic videos. Among the 851 patients who underwent M-TEER, the 1-year survival rate was 86.8%. M-TEER resulted in a significant reduction in both LA volume and estimated systolic pulmonary artery pressure (sPAP) levels (median LA volume: from 123 ml [interquartile range, IQR 92–169 ml] to 104 ml [IQR 78–142 ml], p < 0.001; median sPAP: from 46 mmHg [IQR 35–58 mmHg] to 41 mmHg [IQR 32–54 mmHg], p = 0.036). In contrast, TAPSE remained unchanged (median: from 17 mm [IQR 14–21 mm] to 18 mm [IQR 15–21 mm], p = 0.603). The deep learning model confirmed this finding, showing no significant change in predicted RVEF after M-TEER (median: from 43.1% [IQR 39.1–47.4%] to 43.2% [IQR 39.2–47.2%], p = 0.475). Conclusions While M-TEER improves left-sided haemodynamics, it does not lead to significant RV function recovery, as confirmed by both conventional echocardiography and artificial intelligence. This finding underscores the importance of treating patients before irreversible right heart damage occurs. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1328-8067 67 1 2025 Avoidant/restrictive food intake disorder prognosis and its relation with autism spectrum disorder in Japanese children e70040 EN Chie Tanaka Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayumi Okada Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mana Hanzawa Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chikako Fujii Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshie Shigeyasu Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Sugihara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Makiko Horiuchi Clinical Psychology Section, Department of Medical Support, Okayama University Hospital Takashi Yorifuji Department of Epidemiology, 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 Background: There is a lack of reported clinical factors associated with the outcomes of children and adolescents with avoidant/restrictive food intake disorder (ARFID) in Japan. This study aimed to identify these clinical factors and explore the relationship between ARFID and autism spectrum disorder (ASD). Methods: This retrospective study analyzed data from 48 Japanese children and adolescents with ARFID who visited Okayama University Hospital between January 2011 and March 2022. Clinical characteristics were assessed using medical records and natural history questionnaires. The study compared patients with good and poor prognosis groups and used multiple logistic regression analysis to determine factors influencing prognosis. Results: The study included 33 patients with good prognoses and 15 with poor prognoses. Comorbid ASD was more prevalent in the poor prognosis group (60%) compared to the good prognosis group (21%). Additionally, more than half of the ARFID patients with comorbid ASD were initially undiagnosed. Multivariate analysis revealed that older age at first visit (p = 0.022) and comorbid ASD (p = 0.022) were statistically significant factors associated with poor prognosis in ARFID patients. There were no significant differences in body mass index standard deviation score and maximal weight loss between the two groups. Conclusions: The poor prognosis group had a higher prevalence of comorbid ASD diagnoses. Therefore, it is crucial to evaluate patient's developmental characteristics early in treatment and consider these characteristics throughout the course of care. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0919-8172 32 3 2024 Postoperative infections after robotic‐assisted radical prostatectomy in a single large institution: Effect of type and duration of prophylactic antibiotic administration 258 263 EN Masao Mitsui 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 Naoya Nagasaki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Maruyama Takanori Sekito 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 Kensuke Bekku 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 Objective: We evaluated the incidence of and risk factors for postoperative infections after robotic-assisted radical prostatectomy (RARP) according to the type and duration of prophylactic antibiotic administration. Methods: A total of 1038 patients underwent RARP at our institution from 2010 to 2021; 1026 patients (201 in the cefazolin [CEZ] group and 825 in the ampicillin/sulbactam [ABPC/SBT] group) were analyzed, and 12 who used other antibiotics were excluded. The primary endpoint was the incidence of urinary tract infection (UTI), surgical site infection (SSI), and remote infection (RI). T-tests, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed. Multivariate logistic regression analysis was performed to evaluate the effect of type and duration of prophylactic antibiotic administration. Results: The incidence of UTI was 2.5% (5/201) in the CEZ group and 3.2% (26/825) in the ABPC/SBT group, with no significant difference between groups (p = 0.622). The rates of SSI and RI were comparable between groups (p = 0.680 and 0.906, respectively). Although the duration of antimicrobial therapy was longer in the ABPC/SBT group (p < 0.001), there was no significant difference in the incidence of UTI/SSI/RI after PSM and IPTW (all p > 0.05). Multivariate logistic regression analysis showed that neither the type of antibiotic nor the duration of administration affected the incidence of UTI/SSI/RI. Conclusion: The risk of postoperative UTI/SSI/RI after RARP did not change with the type and duration of antimicrobial therapy. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1880-4276 41 3 2025 Acute effect of multipoint pacing and fused AV delay in patients receiving cardiac resynchronization therapy e70085 EN Masakazu Miyamoto Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nobuhiro Nishii Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomofumi Mizuno Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akira Ueoka Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takuro Masuda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Saori Asada 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 Satoshi Kawada Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Koji Nakagawa 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 Hiroshi Morita Department of Cardiovascular Therapeutics, 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 Background: Cardiac resynchronization therapy (CRT) is an established treatment for patients with heart failure with dyssynchrony. However, one-third of patients do not respond positively to it. Recently, multipoint pacing (MPP), which involves pacing from two sites on the left ventricle, has been found to improve symptoms and hemodynamics compared to conventional CRT. An automatic fused atrioventricular (AV) delay that performs fused pacing for intrinsic conduction has also been introduced. However, the combined effect of MPP and fused AV delay on acute hemodynamics is unknown. Objective: To evaluate the acute hemodynamic effects of MPP and fused AV delay in patients undergoing CRT. Methods: A pressure wire was delivered to the left ventricle, and dp/dt was compared with single atrial stimulation pacing in 52 patients with various pacing configurations. Results: Delta dp/dt was greater in MPP than in conventional CRT (10.5 ± 1.0% vs. 8.2 ± 1.0%, p < 0.001) and in fused AV delay than in short AV delay (10.4 ± 0.8% vs. 8.3 ± 1.1, p < 0.001). Hemodynamic parameters significantly most improved with the combination of MPP and fused AV delay. Delta dp/dt was greater in LV pacing than in biventricular (BiV) pacing with MPP and fused AV delay; however, the delta QRS duration was shorter in LV pacing than in BiV pacing. Delta dp/dt and delta QRS duration were negatively correlated. The super-responder rate was 66%. Conclusion: Combining MPP and fused AV delay has an additional effect. Shortening the QRS duration can increase the dp/dt, but the estimated line differs between LV and BiV pacing. 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.

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.

Wiley Acta Medica Okayama 1861-4728 2025 Alkoxy‐Substituted Anthrabis(Thiadiazole)‐Terthiophene Copolymers for Organic Photovoltaics: A Unique Wavy Backbone Enhances Aggregation, Molecular Order, and Device Efficiency e00678 EN Yi Yan Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroki Mori Research Institute for Interdisciplinary Science, Okayama University Tomoki Yoshino Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ryuki Inami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Jiaxin Chang Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Junqing Gao Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yasushi Nishihara Research Institute for Interdisciplinary Science, Okayama University Two polymer donors, PATz3T-o6BO and PATz3T-o6HD, incorporating alkoxy-substituted anthra[1,2-c:5,6-c′]bis([1,2,5]thiadiazole), were strategically designed and synthesized. The unique wavy backbone of these polymers effectively reduced aggregation, leading to enhanced solubility and significantly improved molecular ordering. Consequently, the PATz3T-o6HD:Y12-based solar cells achieved a power conversion efficiency (PCE) of 7.94%. These findings provide valuable insights into the molecular design of high-performance polymer donors for organic photovoltaics (OPVs). No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0140-7791 2025 Amino Acid Substitutions in Loop C of Arabidopsis PIP2 Aquaporins Alters the Permeability of CO2 EN Shaila Shermin Tania Institute of Plant Science and Resources, Okayama University Shigeko Utsugi Institute of Plant Science and Resources, Okayama University Yoshiyuki Tsuchiya Institute of Plant Science and Resources, Okayama University Shizuka Sasano Institute of Plant Science and Resources, Okayama University Maki Katsuhara Institute of Plant Science and Resources, Okayama University Izumi C. Mori Institute of Plant Science and Resources, Okayama University The transport of CO2 across biomembranes in plant cells is essential for efficient photosynthesis. Some aquaporins capable of CO2 transport, referred to as ‘COOporins’, are postulated to play a crucial role in leaf CO2 diffusion. However, the structural basis of CO2 permeation through aquaporins remains largely unknown. Here, we show that amino acids in loop C are critical for the CO2 permeability of Arabidopsis thaliana PIP2 aquaporins. We found that swapping tyrosine and serine in loop C to histidine and phenylalanine, which differ between AtPIP2;1 and AtPIP2;3, altered CO2 permeability when examined in the Xenopus laevis oocyte heterologous expression system. AlphaFold2 modelling indicated that these substitution induced a conformational shift in the sidechain of arginine in the aromatic/arginine (ar/R) selectivity filter and in lysine at the extracellular mouth of the monomeric pore in PIP2 aquaporins. Our findings demonstrate that distal amino acid substitutions can trigger conformational changes of the ar/R filter in the monomeric pore, modulating CO2 permeability. Additionally, phylogenetic analysis suggested that aquaporins capable of dual water/CO2 permeability are ancestral to those that are water-selective and CO2-impermeable, and CO2-selective and water impermeable. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0014-5793 599 13 2025 Characterization of molecular mechanisms of CaMKKα/1 oligomerization 1914 1924 EN Shun Uenoyama Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Hayato Nitta Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Satomi Ohtsuka Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masaki Magari Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Futoshi Suizu Department of Medical Technology, Kagawa Prefectural University of Health Sciences Hiroshi Tokumitsu Calcium/calmodulin-dependent protein kinase kinase (CaMKK) is an activating kinase for calcium/calmodulin-dependent protein kinase type 1 (CaMKI), calcium/calmodulin-dependent protein kinase type IV (CaMKIV), RAC-alpha serine/threonine-protein kinase (PKB), and AMP-activated protein kinase (AMPK) that has been reported to form an active oligomer in cells. Glutathione S-transferase (GST) pulldown assay from the extracts of COS-7 cells expressing GST- and His6-CaMKKα/1 mutants showed that the C-terminal region containing the autoinhibitory and calmodulin (CaM)-binding sequence (residues 438–463) is required for CaMKKα/1 homo-oligomerization. This was confirmed by the fact that the GST-CaMKKα/1 C-terminal domain (residues 435–505) directly interacted with EGFP-CaMKKα/1 residues 435–505 as well as with wild-type CaMKKα/1. Notably, once oligomerized in cells, CaMKKα/1 is neither exchangeable between the oligomeric complexes nor dissociated by Ca2+/CaM binding. These results support stable oligomerization of CaMKK in the cells by intermolecular self-association of its C-terminal region containing a regulatory domain. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0031-9317 177 4 2025 CNGC2 Negatively Regulates Stomatal Closure and Is Not Required for flg22- and H2O2-Induced Guard Cell [Ca2+]cyt Elevation in Arabidopsis thaliana e70396 EN Rojina Akter Graduate School of Environmental and Life Science, Okayama University Yasuhiro Inoue Graduate School of Environmental and Life Science, Okayama University Saori Masumoto Faculty of Agriculture, Okayama University Yoshiharu Mimata Graduate School of Environmental and Life Science, Okayama University Takakazu Matsuura Institute of Plant Science and Resources, Okayama University Izumi C. Mori Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University In guard cells, cytosolic Ca2+ acts as a second messenger that mediates abscisic acid (ABA)- and pathogen-associated molecular pattern (PAMP)-induced stomatal closure. It was reported that Arabidopsis cyclic nucleotide-gated ion channel 2 (CNGC2) functions as hydrogen peroxide (H2O2)- and PAMP-activated Ca2+-permeable channels at the plasma membrane of mesophyll cells and mediates Ca2+-dependent PAMP-triggered immunity. In this study, we examined the role of CNGC2 in the regulation of stomatal movement because CNGC2 is also expressed in guard cells. We found that stomata of the CNGC2 disruption mutant cngc2-3 are constitutively closed even in the absence of ABA or the flagellar-derived PAMP, flg22. Consistently, leaf temperatures of the cngc2-3 mutant were higher than those of wild-type (WT) plants. The stomatal phenotype of the cngc2-3 mutant was restored by complementation with wild-type CNGC2 under the control of the guard cell preferential promoter, pGC1. Elevation of cytosolic free Ca2+ concentration in guard cells induced by flg22 and H2O2 remained intact in the cngc2-3 mutant. The introduction of the ost1-3 mutation into the cngc2-3 background did not alter the stomatal phenotype. However, the stomatal phenotype of the cngc2-3 mutant was successfully rescued in the double disruption mutant cngc2-3aba2-2. Taken together, these results suggest that CNGC2 negatively regulates stomatal closure response and does not function as flg22– and H2O2-activated Ca2+ channels in guard cells. Though CNGC2 is responsive for H2O2- and flg22-induced [Ca2+]cyt elevation in mesophyll cells, the involvement of CNGC2 in the response to H2O2 and flg22 in guard cells is questionable. 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.

Wiley Acta Medica Okayama 1441-0745 27 3 2025 Factors Influencing Pain Management Practices Among Nurses in University Hospitals in Western Japan: A Cross‐Sectional Study Using Hierarchical Multiple Regression Analysis e70143 EN Mengyao Xi Doctor's Program, Graduate School of Health Sciences, Okayama University Yuki Kajiwara Faculty of Health Sciences, Okayama University Michiko Morimoto Faculty of Health Sciences, Okayama University Effective pain management remains a global nursing challenge, requiring awareness of influencing factors. This cross-sectional study examined such factors among nurses in Western Japan's university hospitals from September to November 2023. A self-reported questionnaire was used to investigate nurses' sociodemographic characteristics, collaboration with physicians in the ward, pain management knowledge, empathy, and pain management practices. Among 695 nurses (69.4% valid response rate), 51.4% had under 5 years' work experience, indicating a relatively junior nursing workforce. The mean practice score was 47.5 (SD = 7.1). Hierarchical regression showed knowledge and empathy increased practice scores by 6.2%. Nurses' empathy, particularly their perspective-taking, explained pain management practice (β = 0.242, p < 0.001). Information-sharing with pain specialists, effective collaboration with physicians in the ward, work experience, and clinical pain education were also associated with pain management practices (all p < 0.05). This study suggests that enhancing nurses' empathy and fostering a collaborative ward environment may be essential strategies to improve the pain management quality. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1433-7851 2025 Development of a Vinylated Cyclic Allene: A Fleeting Strained Diene for the Diels–Alder Reaction e202510319 EN Haruki Mizoguchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takumi Obata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Taiki Hirai Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Manaka Komatsu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Akira Sakakura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Fleeting molecules possessing strained multiple bonds are important components in organic synthesis due to their ability to undergo various chemical reactions driven by the release of strain energy. Although the use of strained π-bonds as 2π components, represented by dienophiles in Diels–Alder reactions, has been well studied, “the strained diene (4π component) approach” for molecular construction remains underexplored. Herein, we report the design of a vinyl cyclic allene (1-vinyl-1,2-cyclohexadiene) as a highly reactive strained diene and the development of its Diels–Alder reactions. Experimental and computational studies of vinyl cyclic allenes revealed that this diene system undergoes cycloaddition with dienophiles regio- and stereoselectively under mild reaction conditions. These studies also provide insight into the reactivity and selectivity of the system. The strained diene approach enables the convergent construction of polycyclic molecules through bond disconnections distinct from conventional retrosynthetic analysis, thus offering an efficient strategy for the assembly of functional molecules. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2378-8038 10 1 2025 Short‐process incudo‐stapedioplasty in congenital ear malformation e70055 EN Ryotaro Omichi Department of Otolaryngology-Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shin Kariya Department of Otolaryngology-Head and Neck Surgery, Kawasaki Medical School Akiko Sugaya Department of Otolaryngology-Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Mizuo Ando Department of Otolaryngology-Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Objectives: Although various stapedotomy and stapedectomy techniques exist, anchoring the piston can be challenging. We present a novel surgical approach for treating congenital stapes malformations with an atypical facial nerve trajectory. Methods: This is a case of a 7-year-old boy presenting with bilateral conductive hearing loss. Prior attempts at tympanoplasty had proven unsuccessful in improving his hearing. Presurgical imaging studies revealed an unusual anatomical configuration, with the facial nerve positioned inferior to the oval window. This anatomical variation precluded the use of conventional prosthesis-anchoring techniques typically employed in stapedotomies. Thus, we devised an innovative approach, opting to anchor the prosthesis to the short process of the incus. Results: This novel technique circumvented the atypical course of the facial nerve, allowing for successful reconstruction of the ossicular chain. The patient demonstrated an acceptable improvement (30 dB gain) in hearing 1-year post-surgery, with no reported complications. Conclusion: This case underscores the critical importance of adapting surgical techniques to address the unique anatomical challenges that may arise in the context of congenital ear malformations. It also highlights the potential of the short process of the incus as a viable alternative anchoring site for stapes prostheses, thereby improving the outcomes of such complex cases. This technique not only restored the patient's hearing but also contributed valuable insights into the management of similar cases, potentially improving the quality of life for individuals with rare and challenging anatomical variations. Level of evidence: 5. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0022-3751 2025 Dual functions of SNAP25 in mouse taste buds EN Kengo Horie Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kuanyu Wang Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hai Huang Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiko Yasumatsu Tokyo Dental Junior College Yuzo Ninomiya Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihiro Mitoh Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryusuke Yoshida Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Type III cells in mouse taste buds are considered to transmit aversive stimuli, such as sourness, to the gustatory nerve through vesicular synapses. Synaptosome-associated protein 25 (SNAP25) might contribute to synaptic vesicular release in sour sensation, although direct evidence has been lacking. Here, we demonstrated that epithelia-specific Snap25 conditional knockout (cKO) mice exhibited a significant reduction in the number of type III cells. Notably, the proportion of 5-ethynyl 2′-deoxyuridine-positive post-mitotic type III cells in Snap25 cKO mice was significantly lower on tracing day 14, but not at day 7, which suggests that SNAP25 contributes to the maintenance of type III cells. In a short-term lick test, Snap25 cKO (sour taste absent) and Snap25/ transient receptor potential vanilloid 1 double KO (sour taste and somatosensory absent) mice exhibit a significantly higher lick response to sour tastants, confirming the role of SNAP25 for sour sensation. Electrophysiological recordings of the chorda tympani nerve reveal nearly abolished ammonium and sour taste responses in Snap25 cKO mice, which concludes sour-dependent synapse transmission in type III cells. Overall, these data suggest that vesicular synapses in taste buds are indispensable for transmission of information from, and the replenishment of, sour-sensitive type III taste cells. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1462-2912 27 6 2025 Sulphur‐Acquisition Pathways for Cysteine Synthesis Confer a Fitness Advantage to Bacteria in Plant Extracts e70126 EN Kazuya Ishikawa Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Saki Yamaguchi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taketo Tsukaoka Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Makoto Tsunoda Graduate School of Pharmaceutical Sciences, The University of Tokyo Kazuyuki Furuta Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chikara Kaito Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Bacteria and plants are closely associated with human society, in fields such as agriculture, public health, the food industry, and waste disposal. Bacteria have evolved nutrient-utilisation systems adapted to achieve the most efficient growth in their major habitats. However, empirical evidence to support the significance of bacterial nutrient utilisation in adaptation to plants is limited. Therefore, we investigated the genetic and nutritional factors required for bacterial growth in plant extracts by screening an Escherichia coli gene-knockout library in vegetable-based medium. Mutants lacking genes involved in sulphur assimilation, whereby sulphur is transferred from sulphate to cysteine, exhibited negligible growth in vegetable-based medium or plant extracts, owing to the low cysteine levels. The reverse transsulphuration pathway from methionine, another pathway for donating sulphur to cysteine, occurring in bacteria such as Bacillus subtilis, also played an important role in growth in plant extracts. These two sulphur-assimilation pathways were more frequently observed in plant-associated than in animal-associated bacteria. Sulphur-acquisition pathways for cysteine synthesis thus play a key role in bacterial growth in plant-derived environments such as plant residues and plant exudates. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0361-8609 2025 International Consensus Histopathological Criteria for Subtyping Idiopathic Multicentric Castleman Disease Based on Machine Learning Analysis EN Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Tomoka Haratake Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yoshito Nishimura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Remi Sumiyoshi The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease, TAFRO and Related Ddisease Research Group Hideki Ujiie Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yuri Kawahara Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Tomohiro Koga The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease, TAFRO and Related Ddisease Research Group Masao Ueki School of Information and Data Sciences, Nagasaki University Dorottya Laczko Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania Eric Oksenhendler Department of Clinical Immunology, Hôpital Saint-Louis David C. Fajgenbaum Center for Cytokine Storm Treatment and Laboratory, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania Frits van Rhee Myeloma Center, University of Arkansas for Medical Sciences Atsushi Kawakami The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease, TAFRO and Related Ddisease Research Group Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder classified into three recognized clinical subtypes—idiopathic plasmacytic lymphadenopathy (IPL), TAFRO, and NOS. Although clinical criteria are available for subtyping, diagnostically challenging cases with overlapping histopathological features highlight the need for an improved classification system integrating clinical and histopathological findings. We aimed to develop an objective histopathological subtyping system for iMCD that closely correlates with the clinical subtypes. Excisional lymph node specimens from 94 Japanese iMCD patients (54 IPL, 28 TAFRO, 12 NOS) were analyzed for five key histopathological parameters: germinal center (GC) status, plasmacytosis, vascularity, hemosiderin deposition, and “whirlpool” vessel formation in GC. Using hierarchical clustering, we visualized subgroups and developed a machine learning-based decision tree to differentiate the clinical subtypes and validated it in an external cohort of 12 patients with iMCD. Hierarchical cluster analysis separated the IPL and TAFRO cases into mutually exclusive clusters, whereas the NOS cases were interspersed between them. Decision tree modeling identified plasmacytosis, vascularity, and whirlpool vessel formation as key features distinguishing IPL from TAFRO, achieving 91% and 92% accuracy in the training and test sets, respectively. External validation correctly classified all IPL and TAFRO cases, confirming the reproducibility of the system. Our histopathological classification system closely aligns with the clinical subtypes, offering a more precise approach to iMCD subtyping. It may enhance diagnostic accuracy, guide clinical decision-making for predicting treatment response in challenging cases, and improve patient selection for future research. Further validation of its versatility and clinical utility is required. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1526-9914 26 6 2025 Quantitative quality control of 3D water tank using image analysis e70119 EN Yuki Tanimoto Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center Kohei Sugimoto Department of Radiological Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare Kazunobu Koshi Department of Radiology, NHO Fukuyama Medical Center Akira Hiroshige 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 Daiki Nakanishi Division of Radiology, Department of Medical Technology, Kyushu University Hospital Hirofumi Honda Department of Radiological Technology, Ehime University Hospital Masataka Oita Department of Healthcare Science, Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Background and objective: Accurate beam data acquisition using three-dimensional (3D) water tanks is essential for beam commissioning and quality control (QC) in clinical radiation therapy. This study introduces a novel method for quantitative QC of the system, utilizing MV images and webcam videos. The stability of the motor drive speed and the positional accuracy of the fixture were evaluated under two measurement modes: “continuous mode” and “step-by-step mode.” Methods: A TRUFIX mounting system (PTW Freiburg Inc., Germany) was used to attach the center of the steel ball to its top, ensuring alignment with the water surface of the tank. To assess deviations from the radiation isocenter, MV images were acquired and compared with digitally reconstructed radiographs (DRRs). These evaluations were performed at different speed settings (slow, medium, and fast) using ET CT Body Marker (BRAINLAB Inc., USA) mounted on the drive unit. A webcam was utilized to capture the images, and custom-developed tracking software was employed to analyze deviations in driving speed and positional errors. Results: The mean error of the radiation isocenter was 0.37 ± 0.09 mm. As the motor drive speed increased, the discrepancy between the set speed and the actual speed observed in the analysis also became larger. In “continuous mode,” the deviation from the displayed value was greater than that observed in “step-by-step mode.” Conclusion: It is demonstrated that the proposed analysis method can quantitatively evaluate radiation isocenter misalignment, tank setup position deviation, and both the indicated drive speed values and their stability. At higher drive speeds, the “step-by-step mode” showed smaller deviations from the indicated values. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0385-5600 2025 Lytic Transglycosylase Deficiency Increases Susceptibility to β-lactam Antibiotics But Reduces Susceptibility to Vancomycin in Escherichia coli EN Takahiko Kimura Laboratory of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kazuya Ishikawa Laboratory of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Ryosuke Nakagawa Laboratory of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kazuyuki Furuta Laboratory of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Chikara Kaito Laboratory of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University In Staphylococcus aureus, a gram-positive pathogen, vancomycin-resistant strains become susceptible to β-lactam antibiotics, referred to as the “seesaw effect.” However, in gram-negative bacteria, the phenomenon is less clear. Here, we analyzed the gene-knockout effects of eight lytic transglycosylases (slt, mltA, mltB, mltC, mltD, mltE, mltF, mltG) on antibiotic sensitivity in Escherichia coli. Knockout of both slt and mltG increased sensitivity to β-lactam antibiotics and reduced sensitivity to vancomycin. The β-lactam antibiotic sensitivity and vancomycin resistance of the slt-knockout mutant were abolished by the introduction of the wild-type slt gene but remained unchanged by the introduction of the mutant slt gene encoding an amino acid substitution variant of the transglycosylase catalytic centre. The double-knockout strain for slt and mltB was more sensitive to ampicillin and more resistant to vancomycin than each single-knockout strain. The double-knockout strain for slt and mltG was more sensitive to ampicillin and more resistant to vancomycin than each single-knockout strain. These results suggest that loss of lytic transglycosylase activity causes β-lactam antibiotic sensitivity and vancomycin resistance in E. coli. 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.

Wiley Acta Medica Okayama 0041-1132 2025 Novel method of leukocytapheresis using a highly concentrated sodium citrate solution alternative to acid citrate dextrose solution A EN Masaya Abe Division of Transfusion and Cell Therapy, Okayama University Hospital Keiko Fujii Division of Clinical Laboratory, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Wataru Kitamura Division of Transfusion and Cell Therapy, Okayama University Hospital Kazuhiro Ikeuchi Division of Transfusion and Cell Therapy, Okayama University Hospital Takuya Fukumi Division of Transfusion and Cell Therapy, Okayama University Hospital Kana Washio Department of Pediatric Hematology and Oncology, Okayama University Hospital Fumio Otsuka Division of Clinical Laboratory, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Division of Transfusion and Cell Therapy, Okayama University Hospital Background: Large-volume leukocytapheresis is time consuming. The upper limit of the inlet flow rate is determined by the inlet: anticoagulant (AC) ratio and can be changed by combining the AC with heparin. Here, we devised a protocol to increase the AC ratio using a highly concentrated sodium citrate solution without heparin. Study Design and Methods: We collected data from 40 consecutive apheresis procedures performed using the Spectra Optia system on 40 donors for allogeneic peripheral blood stem cells between June 2022 and June 2023. We used AC containing 2.2% sodium citrate (normal concentrated sodium citrate [NSC]) and 5.32% sodium citrate (highly concentrated sodium citrate [HSC]). The AC ratios were set to 12:1 and 24:1 for the NSC and HSC, respectively. Results: The processed volume was not different; the maximum inlet flow rate increased, the total processing time was reduced, the AC solution used was reduced, and the product volume was reduced in the HSC group, compared to the NSC group. Although the CD34+ cell CE2 was reduced in the HSC group, no difference was observed in the number of collected CD34+ cells. The incidences of citrate-related reactions were similar. Discussion: We propose a novel leukocytapheresis method using HSC that shortens the procedure time and reduces the amount of AC solution used compared to the conventional method No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2193-5807 2025 2-Hydroxy-3-(Pyrrolidin-1-yl)-Indolines: A Platform for Accessing Decorated Deaminokynurenines Enabled by a Double Tautomeric Control e202500439 EN Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University In this study we introduce indoline hemiaminals as phenacyl bromide surrogates for the synthesis of deaminokynurenine derivatives through cyclic-linear tautomeric intermediates. The reaction proceeds through a tandem process involving the ring opening of indoline hemiaminals, generating transient acyclic aldehydes which are then trapped with in situ generated enolate species. Our protocol overcomes traditional dilemma in production of polar-mismatch 1,4-dicarbonyl compounds by utilizing a transient highly electrophilic linear aldehyde and late-stage transposition of carbonyl moiety. The synthetic utility of our transformation was demonstrated by follow-up transformations, including the first total synthesis of quinoline-2,4-dione alkaloid. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0306-5251 2025 Comprehensive analysis of adverse event profile changes with pertuzumab addition to trastuzumab‐based breast cancer therapy: Disproportionality analysis using VigiBase EN Tatsuaki Takeda Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Jun Matsumoto Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Tomonori Sakai Department of Pharmacy, Okayama University Hospital Naohiro Iwata Department of Pharmacy, Okayama University Hospital Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Noritaka Ariyoshi Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Aims: Pertuzumab is used in combination with trastuzumab-based therapy for HER2-positive breast cancer. However, real-world safety information on pertuzumab remains limited. This study assessed the safety of adding pertuzumab to trastuzumab-based therapy for HER2-positive breast cancer using real-world data. Methods: VigiBase, the World Health Organization's global database of adverse events (AEs), containing reports from November 1967 to December 2023, was used. Signals for pertuzumab-associated AEs in breast cancer cases were detected using the reporting odds ratio (ROR). Results: Signals of trastuzumab plus pertuzumab relative to trastuzumab alone were detected in gastrointestinal disorders (ROR: 1.45, 95% confidence interval: 1.26–1.67), including diarrhoea (3.49, 2.83–4.30); infections and infestations (1.54, 1.24–1.91); and skin and subcutaneous tissue disorders (ROR: 1.63, 1.40–1.90), including pruritus (1.96, 1.51–2.55) and rash (1.63, 1.20–2.23). Further, signals of trastuzumab plus docetaxel plus pertuzumab relative to those of trastuzumab plus docetaxel were detected in gastrointestinal disorders (1.63, 1.38–1.93), including nausea (1.72, 1.24–2.39) and vomiting (1.48, 1.01–2.17), and in nervous system disorders (1.50, 1.20–1.87), including paraesthesia (2.60, 1.33–5.08) and peripheral sensory neuropathy (5.94, 1.79–19.71). The frequency of AEs causing or prolonging hospitalization was increased with trastuzumab plus pertuzumab compared to that with trastuzumab alone (1.18, 1.00–1.38). Conclusions: AE profiles after the addition of pertuzumab to trastuzumab-based therapy were comprehensively identified. The findings in this study highlight the importance of considering these AEs when selecting pertuzumab combination therapy to ensure the safety of patients with breast cancer. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1744-9979 29 3 2025 Text mining for case report articles on “peritoneal dialysis” from PubMed database 459 470 EN Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naruhiko Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Haraguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kitamura 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 Introduction: The number of published medical articles on peritoneal dialysis (PD) has been increasing, and efficiently selecting information from numerous articles can be difficult. In this study, we examined whether artificial intelligence (AI) text mining can be a good support for efficiently collecting PD information. Methods: We performed text mining and analyzed all the abstracts of case reports on PD in the PubMed database. In total, 3137 case reports with abstracts related to “peritoneal dialysis” published from 1970 to 2021 were identified. Results: A total of 280 347 relevant words were extracted from all the abstracts. Word frequency analysis, word dependency analysis, and word frequency transition analysis showed that peritonitis, encapsulating peritoneal sclerosis, and child have been important keywords. Theseanalyses not only reflected historical background but also anticipated future trends of PD study. Conclusion: These suggest that text mining can be a good support for efficiently collecting PD information. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1464-6722 26 5 2025 Genomic Islands of Pseudomonas syringae pv. tabaci 6605: Identification of PtaGI-1 as a Pathogenicity Island With Effector Genes and a Tabtoxin Cluster e70087 EN Yuta Watanabe The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kotomi Kunishi Faculty of Agriculture,Okayama University Hidenori Matsui The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nanami Sakata The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiteru Noutoshi The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuhiro Toyoda The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuki Ichinose The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Genomic islands (GIs) are 20-500 kb DNA regions that are thought to be acquired by horizontal gene transfer. GIs that confer pathogenicity and environmental adaptation have been reported in Pseudomonas species; however, GIs that enhance bacterial virulence have not. Here, we identified 110 kb and 103 kb GIs in P. syringae pv. tabaci 6605 (Pta6605), the causative agent of tobacco wildfire disease, which has the ability to produce tabtoxin as a phytotoxin. These GIs are partially homologous to known genomic islands in Pseudomonas aeruginosa and P. syringae pv. phaseolicola and were designated PtaGI-1 and PtaGI-2. Both PtaGIs conserve core genes, whereas each GI possesses different accessory genes. PtaGI-1 contains a tabtoxin biosynthetic gene cluster and three type III effector genes among its accessory genes, whereas PtaGI-2 also contains homologous genes to hsvABC, pathogenicity-related genes in Erwinia amylovora. Inoculation revealed that the PtaGI-1 mutant, but not the PtaGI-2 mutant, lost the ability to biosynthesise tabtoxin and to cause disease. Therefore, PtaGI-1 is thought to be a pathogenicity island. Both PtaGI-1 and PtaGI-2 have a pseudogene of tRNALys on the left border and an intact tRNALys gene on the right border. In a colony of Pta6605, both GIs can be excised at tRNALys, and PtaGI-1 and PtaGI-2 exist in a circular form. These results indicate that tabtoxin biosynthesis genes in PtaGI-1 are required for disease development, and PtaGI-1 is necessary for Pta6605 virulence. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1464-6722 26 5 2025 Pseudomonas syringae pv. tabaci 6605 Requires Seven Type III Effectors to Infect Nicotiana benthamiana e70091 EN Kana Kuroe Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takafumi Nishimura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sachi Kashihara Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nanami Sakata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mikihiro Yamamoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiteru Noutoshi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuhiro Toyoda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuki Ichinose Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hidenori Matsui Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Type III effectors (T3Es), virulence factors injected into plant cells via the type III secretion system (T3SS), play essential roles in the infection of host plants. Pseudomonas syringae pv. tabaci 6605 (Pta 6605) is the causal agent of wildfire disease in tobacco and harbours at least 22 T3Es in its genome. However, the specific T3Es required by Pta 6605 to infect Nicotiana benthamiana remain unidentified. In this study, we investigated the T3Es that contribute to Pta 6605 infection of N. benthamiana. We constructed Pta 6605 poly-T3E-deficient mutants (Pta DxE) and inoculated them into N. benthamiana. Flood assay, which mimics natural opening-based entry, showed that mutant strains lacking 14-22 T3Es, namely, Pta D14E-D22E mutants, exhibited reduced disease symptoms. By contrast, infiltration inoculation, which involves direct injection into leaves, showed that the Pta D14E to Pta D20E mutants developed disease symptoms. Notably, the Pta D20E, containing AvrE1 and HopM1, induced weak but observable symptoms upon infiltration inoculation. Conversely, no symptoms were observed in either the flood assay or infiltration inoculation for Pta D21E and Pta D22E. Taken together, these findings indicate that the many T3Es such as AvrPto4/AvrPtoB, HopW1/HopAE1, and HopM1/AvrE1 in Pta 6605 collectively contribute to invasion through natural openings and symptom development in N. benthamiana. This study provides the basis for understanding virulence in the host by identifying the minimum T3E repertoire required by Pta 6605 to infect N. benthamiana. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 116 5 2025 High Antigenicity for Treg Cells Confers Resistance to PD-1 Blockade Therapy via High PD-1 Expression in Treg Cells 1214 1226 EN Hiroaki Matsuura Department of Tumor Microenvironment, Okayama University Takamasa Ishino Department of Tumor Microenvironment, Okayama University Toshifumi Ninomiya Department of Tumor Microenvironment, Okayama University Kiichiro Ninomiya Department of Hematology, Oncology and Respiratory Medicine,Okayama University Kota Tachibana Department of Dermatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akiko Honobe-Tabuchi Department of Dermatology, University of Yamanashi Yoshinori Muto Department of Dermatology, University of Yamanashi Takashi Inozume Department of Dermatology, University of Yamanashi Youki Ueda Department of Tumor Microenvironment, Okayama University Kadoaki Ohashi Department of Hematology, Oncology and Respiratory Medicine,Okayama University Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine,Okayama University Joji Nagasaki Department of Tumor Microenvironment, Okayama University Yosuke Togashi Department of Tumor Microenvironment, Okayama University Regulatory T (Treg) cells have an immunosuppressive function, and programmed death-1 (PD-1)-expressing Treg cells reportedly induce resistance to PD-1 blockade therapies through their reactivation. However, the effects of antigenicity on PD-1 expression in Treg cells and the resistance to PD-1 blockade therapy remain unclear. Here, we show that Treg cells gain high PD-1 expression through an antigen with high antigenicity. Additionally, tumors with high antigenicity for Treg cells were resistant to PD-1 blockade in vivo due to PD-1+ Treg-cell infiltration. Because such PD-1+ Treg cells have high cytotoxic T lymphocyte antigen (CTLA)-4 expression, resistance could be overcome by combination with an anti-CTLA-4 monoclonal antibody (mAb). Patients who responded to combination therapy with anti-PD-1 and anti-CTLA-4 mAbs sequentially after primary resistance to PD-1 blockade monotherapy showed high Treg cell infiltration. We propose that the high antigenicity of Treg cells confers resistance to PD-1 blockade therapy via high PD-1 expression in Treg cells, which can be overcome by combination therapy with an anti-CTLA-4 mAb. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2769-2558 4 2 2025 Olanzapine enabled rechallenge after lorlatinib-induced psychosis: A case report e70091 EN Akiyoshi Yokode Department of Neuropsychiatry, Okayama University Hospital Masaki Fujiwara Department of Neuropsychiatry, Okayama University Hospital Yuko Nakamura Department of Neuropsychiatry, Okayama University Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Shinji Sakamoto Department of Neuropsychiatry, Okayama University Hospital Manabu Takaki Department of Neuropsychiatry, Okayama University Graduate School of Medicine,Dentistry, and Pharmaceutical Sciences Background: Lorlatinib is a third-generation tyrosine kinase inhibitor for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). While it has a high intracranial lesion control rate, it can also cause central nervous system complications, including psychotic symptoms. We present a case of lorlatinib-induced psychosis successfully managed with olanzapine, enabling lorlatinib rechallenge. Case Presentation: A 32-year-old woman with ALK-positive NSCLC and brain metastases was started on lorlatinib. After 18 months, she developed hallucinations and delusions. Despite treatment with risperidone, her psychotic symptoms persisted, leading to hospitalization. Her symptoms resolved upon lorlatinib discontinuation while risperidone was continued. Given the critical role of lorlatinib in controlling brain metastases, rechallenge was considered. To mitigate concerns regarding drug interactions, risperidone was replaced with olanzapine. Following lorlatinib rechallenge with olanzapine, no recurrence of psychiatric symptoms was observed, allowing continued lorlatinib treatment. Additionally, no progression of lung cancer was noted. Conclusion: Lorlatinib is an essential drug for controlling brain metastases in ALK-positive NSCLC. However, it can induce psychotic symptoms. When psychiatrists are involved in managing adverse effects during cancer treatment, close collaboration among oncologists, psychiatrists, and patients is essential. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 13 4 2025 A Case of a Metal Foreign Object Remaining in the Maxillary Bone for an Extended Period: A Case Report e9631 EN Koichi Kadoya Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuki Kunisada Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kyoichi Obata Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroaki Takakura Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tatsuo Ogawa Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences We report a rare case in which a metallic foreign body remained undetected in a patient's maxilla for nearly 40 years after a childhood bicycle accident. Despite the accident, the implant remained in place without causing infection due to the lack of imaging studies at the time. The metal was accidentally discovered during a routine dental imaging examination 40 years later and subsequently surgically removed. This case highlights the importance of comprehensive imaging and the dangers of overlooking foreign bodies, especially in the vulnerable head and neck region. The patient, 53 years old at the time of discovery, presented to the dentist due to discomfort in the palate and nasal cavity. During this visit, radiographs were taken and a foreign body was discovered. Surgical removal of the foreign body revealed significant corrosion and surrounding granulation tissue indicative of foreign body granuloma. Elemental analysis of the foreign body confirmed that it was an iron-based metal, unlike biocompatible materials such as titanium. These findings reinforce the need for close post-trauma evaluation and follow-up, especially in cases of pediatric trauma, to avoid the possibility of long-term complications arising from unnoticed foreign bodies in anatomically significant areas. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2769-2558 4 2 2025 A case report of ineffective electroconvulsive therapy for chronic pain e70108 EN Takashi Fukao Department of Neuropsychiatry, Okayama University Hospital Masaki Fujiwara Department of Neuropsychiatry, Okayama University Hospital Yuto Yamada Department of Neuropsychiatry, Okayama University Hospital Kazushi Asada Department of Neuropsychiatry, Okayama University Hospital Takahiro Asada Department of Neuropsychiatry, Okayama University Hospital Hirotoshi Ri Department of Neuropsychiatry, Okayama University Hospital Shinji Sakamoto Department of Neuropsychiatry, Okayama University Hospital Manabu Takaki Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Background: Somatic symptom disorder (SSD), which includes chronic pain, is a common mental disorder characterized by significant functional impairment and other psychiatric comorbidities. Electroconvulsive therapy (ECT) has been proposed as a potential treatment for refractory chronic pain. However, evidence supporting its efficacy is limited and/or low quality. We present a case of SSD with chronic pain in which ECT was ineffective. Case Presentation: The patient was a 63-year-old man with chronic pain in the lower back, buttocks, thighs, and soles of the feet. The duration of his chronic pain was 3.8 years. He was diagnosed with Bertolotti's syndrome and SSD. He did not meet the criteria for major depressive disorder. He kept physically active by walking and doing exercises to distract himself from his pain. He strongly perceived pain as a physical issue and preferred ECT over psychotherapy. Despite undergoing 10 ECT sessions with adequate seizures, his pain persisted. After four sessions, he experienced despair over the lack of improvement in pain, which temporarily intensified his suicidal ideation. After undergoing ECT, he continued to maintain his activities, including walking and exercise, while his catastrophic thinking about pain persisted. Conclusion: The ineffectiveness of ECT in this case highlights the need for balanced counseling, particularly for patients who consider ECT a last-resort treatment. Psychological monitoring and depression screening are essential, especially given the risk of heightened despair or suicidal ideation when ECT is ineffective. Therefore, collaborative decision-making based on accurate information is vital. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2045-7634 14 8 2025 Genomic Differences and Distinct TP53 Mutation Site-Linked Chemosensitivity in Early- and Late-Onset Gastric Cancer e70793 EN Tomohiro Kamio Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiyasu Kono Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kensuke Hirosuna Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiki Ozato Department of Gastroenterology, Okayama University Hospital 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 Motoyuki Otsuka Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Gastric cancer (GC) in younger patients often exhibits aggressive behavior and a poorer prognosis than that in older patients. Although the clinical differences may stem from oncogenic gene variations, it is unclear whether genetic differences exist between these groups. This study compared the genetic profiles of early- and late-onset GC and evaluated their impact on treatment outcomes. Methods: We analyzed genetic data from 1284 patients with GC in the Japanese nationwide Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, comparing early-onset (<= 39 years; n = 143) and late-onset (>= 65 years; n = 1141) groups. The influence of TP53 mutations on the time to treatment failure (TTF) with platinum-based chemotherapy and the sensitivity of cancer cells with different TP53 mutation sites to oxaliplatin were assessed in vitro. Results: Early- and late-onset GC showed distinct genetic profiles, with fewer neoantigen-associated genetic changes observed in early-onset cases. In particular, TP53 has distinct mutation sites; R175H and R273 mutations are more frequent in early- and late-onset GC, respectively. The R175H mutation showed higher sensitivity to oxaliplatin in vitro, consistent with the longer TTF in early-onset patients (17.3 vs. 7.0 months, p = 0.013) when focusing on the patients with TP53 mutations. Conclusion: Genomic differences, particularly in TP53 mutation sites, between early- and late-onset GC support the need for age-specific treatment strategies. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2397-9070 9 4 2025 Frequency and Characteristics of Gastrointestinal Diseases in Patients With Neurofibromatosis e70151 EN Manami Honda Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasushi Yamasaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy,Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background and Aim: Patients with neurofibromatosis (NF) frequently experience gastrointestinal symptoms, but the specific characteristics of these lesions are not well understood. Methods: To investigate the prevalence and nature of gastrointestinal diseases in this population, we analyzed the gastrointestinal lesions identified through endoscopic examinations in patients with NF. Results: We included 225 patients with NF type 1 (NF1) and 15 with NF type 2 (NF2). None of the NF2 patients underwent endoscopy. Among the NF1 patients, 27 received endoscopies, and 13 (59%) had gastrointestinal lesions. These 13 patients were predominantly male (10 males and three females), with a median age of 53 years (range: 19-76 years). The identified lesions included colorectal polyps (n = 6), gastrointestinal stromal tumors ([GIST], n = 4), subepithelial lesions (n = 3), gastric fundic gland polyps (n = 3), diffuse intestinal ganglioneuromatosis (n = 2), esophageal polyps (n = 2), a Schwann cell hamartoma (n = 1), esophageal cancer (n = 1), and a gastric hyperplastic polyp (n = 1). All GISTs and one case of diffuse intestinal ganglioneuromatosis were surgically resected. Interestingly, six out of 13 patients were asymptomatic. Additionally, all patients who required surgery were 40 years of age or older. Conclusions: These findings suggest that routine endoscopic examinations, along with imaging techniques like computed tomography and magnetic resonance imaging, could be beneficial for the early detection of gastrointestinal lesions in NF1 patients aged 40 and above. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2397-9070 9 4 2025 Induction Therapy With Oral Tacrolimus Provides Long-Term Benefit in Thiopurine-Naïve Refractory Ulcerative Colitis Patients Despite Low Serum Albumin Levels e70139 EN Shoko Igawa Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshihiro Inokuchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junki Toyosawa Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Aoyama Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasushi Yamasaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideaki Kinugasa Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Takahara Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, 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 Aim: Oral tacrolimus is an effective treatment for refractory ulcerative colitis (UC). However, tacrolimus is underutilized because of the difficulties in transitioning to subsequent maintenance therapy and concerns about adverse events. Methods: We evaluated the clinical outcomes, adverse events, and accumulated medication costs in consecutive 72 UC patients treated with tacrolimus. Results: Fifty-five (76%) patients with pancolitis and 43 (60%) patients with acute severe disease were entered. Fifty-four (75%) achieved clinical remission 8 weeks after starting tacrolimus. At the last visit, 62 (86%) patients had colectomy-free remission, and 55 (76%) patients had corticosteroid-free remission. Eighteen (25%) patients maintained remission without additional treatment after tacrolimus discontinuation. Patients with continuous remission had a significantly lower history of thiopurine use and lower serum albumin levels at the induction of tacrolimus than patients with failure to induce or maintain remission. No severe adverse events due to tacrolimus treatment were observed. The accumulated medication costs over 3 years in patients with continuous remission after the start of tacrolimus were lower than those in patients with induction and maintenance of infliximab (p < 0.001). Conclusions: Tacrolimus could have an irreplaceable role in the era of biologic therapies, especially for refractory UC patients with thiopurine-na & iuml;ve and low serum albumin levels. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 2025 Novel Therapeutic Algorism in Patients With Anterior Cutaneous Nerve Entrapment Syndrome EN Yoshitaka Kondo 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 Ami Kobayashi Department of Neurology, Brigham and Women's Hospital, Harvard Medical School Kyosuke Arakawa Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine Yoshikazu Matsuoka Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine Yudai Mimata 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 Kunitoshi Shigeyasu 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 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 Background: Anterior cutaneous nerve entrapment syndrome (ACNES) is often overlooked as a cause of chronic abdominal pain. Trigger point injections (TPIs) serve as both a diagnostic and therapeutic tool. Although neurectomy is frequently chosen for patients with severe ACNES, its surgical outcomes remain unclear. Aim: This study aims to evaluate both the short- and long-term outcomes for neurectomy and propose a novel therapeutic algorithm. Methods: A cohort of postoperative patients presenting with ACNES between 2016 and 2023 was retrospectively evaluated. Patients received a single diagnostic TPI. When the pain subsided, an anterior neurectomy was performed using either an anterior or laparoscopic approach. Pain scores were assessed using the numeric rating scale (NRS). Results: Among 37 patients (60% females, mean age 33.8 ± 3.4 years), 29 patients (78.4%) experienced pain recurrence following initial neurectomy. Of these, 22 patients underwent repeat neurectomies, resulting in complete remission in 15 patients and no benefit in 7 patients. Long-term outcomes showed that 62.2% achieved clinical remission (NRS = 0), whereas 8.1% reported reduced but persistent pain (NRS 1–2). Preoperative TPI effectiveness was a strong predictor of surgical success, with patients achieving post-TPI NRS (0–1) significantly more likely to attain remission (p = 0.0074). Older age was also associated with higher remission rates (p = 0.0476). Conclusion: TPI is critical for predicting neurectomy success. These findings support the integration of preoperative TPI evaluation and tailored surgical strategies to optimize outcomes for patients with ACNES. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2052-8817 12 1 2025 Association of blood carboxyhemoglobin levels with mortality and neurological outcomes in out-of-hospital cardiac arrest e70053 EN Takashi Hongo 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 Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohiro Hiraoka Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuya Murakami 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 Toshiyuki Aokage 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: Carbon monoxide (CO), produced endogenously by heme oxygenase-1, plays a crucial role in the immune system by mitigating cellular damage under stress. However, the significance of carboxyhemoglobin (COHb) levels after out-of-hospital cardiac arrest (OHCA) is not well understood. This study aimed to explore the association between COHb levels at hospital arrival and within the first 24 h post-arrival with 30-day mortality and neurological outcomes in patients who experienced OHCA. Methods: This single-center, retrospective study analyzed data from adult patients who experienced OHCA seen at Okayama University Hospital from 2019 to 2023. The patients were assigned to one of two study groups based on COHb levels (0.0% or >= 0.1%) upon hospital arrival. The primary outcome was 30-day mortality. Results: Among the 560 eligible patients who experienced OHCA, 284 (50.7%) were in the COHb 0.0% group and 276 (49.3%) were in the COHb >= 0.1% group. The 30-day mortality was significantly higher in the COHb 0.0% group compared to the COHb >= 0.1% group (264 [92.9%] vs. 233 [84.4%]). Multivariable logistic regression showed that the COHb 0.0% group was associated with 30-day mortality (adjusted ORs: 2.24, 95% CIs: 1.10-4.56). Non-survivors at 30 days who were admitted to the intensive care unit had lower COHb levels at hospital arrival (0.0% vs. 0.2%) and lower mean COHb levels during the first 24 h post-arrival (0.7% vs. 0.9%) compared to survivors. Conclusions: COHb levels of 0.0% were linked to worse outcomes in patients experiencing OHCA, warranting further research on the prognostic implications of COHb in this context. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2692-4609 5 1 2025 Endoscopic ultrasonography-guided removal of a stent that had migrated into the pancreas post-pancreaticojejunostomy: A case report e70096 EN Satoshi Kajitani Department of Gastroenterology andHepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology andHepatology, Okayama University Hospital Kentaro Oki Department of Gastroenterology andHepatology, Okayama University Hospital Akihiro Matsumi Department of Gastroenterology andHepatology, Okayama University Hospital Kazuya Miyamoto Department of Gastroenterology andHepatology, Okayama University Hospital Yuki Fujii Department of Gastroenterology andHepatology, Okayama University Hospital Daisuke Uchida Department of Gastroenterology andHepatology, Okayama University Hospital Koichiro Tsutsumi Department of Gastroenterology andHepatology, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology andHepatology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology andHepatology, Okayama University Hospital A 64-year-old woman had undergone subtotal stomach-preserving pancreaticoduodenectomy for locally advanced pancreatic head cancer. She had an uneventful postoperative course with no recurrence. However, approximately 18 months after surgery, she presented with recurrent abdominal pain. Although contrast-enhanced computed tomography abdominal radiographs showed internal stent migration to the residual pancreas, dilatation of the tail side of the pancreatic duct was observed. The impaired internal stent was considered to be the cause of the abdominal pain. An attempt to remove the stent via balloon-assisted endoscopy was unsuccessful as the pancreaticojejunostomy site could not be reached. Consequently, endoscopic ultrasonography-guided pancreatic duct drainage was performed, and a plastic stent was placed through the jejunal site to the stomach. Two months later, the endosonographically/endoscopic ultrasonography-guided created route was dilated, and an endoscopic introducer was inserted into the pancreatic duct. Biopsy forceps were advanced through the sheath, allowing the successful removal of the stent by direct grasping. The symptoms of the patient improved, and she was discharged without complications. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2769-2558 4 1 2025 A case of invasive pulmonary aspergillosis associated with clozapine-induced agranulocytosis e70077 EN Akiyoshi Yokode Department of Neuropsychiatry, Okayama University Hospital Masaki Fujiwara Department of Neuropsychiatry, Okayama University Hospital Toshiki Terao Department of Hematology and Oncology, Okayama University Hospital Shinji Sakamoto Department of Neuropsychiatry, Okayama University Hospital Yuto Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryota Sato Okayama Psychiatric Medical Center Momoko Mishima Okayama Psychiatric Medical Center Yuji Yada Okayama Psychiatric Medical Center Ken-Ichi Matsuoka Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: Clozapine-induced agranulocytosis (CLIA) is a rare but serious complication. Fever associated with CLIA is typically treated with broad-spectrum antimicrobials, but empiric antifungal therapy is rarely used. While bacterial and viral infections have been reported in CLIA cases, no cases of fungal infections complicated by CLIA have been documented. We report the first case of CLIA complicated by invasive pulmonary aspergillosis (IPA) in a patient with schizophrenia. The diagnosis of IPA was made using serum beta-D-glucan, Aspergillus galactomannan antigen tests, and chest computed tomography (CT). Case presentation: We present a case of a 51-year-old man with schizophrenia who developed CLIA complicated by IPA. The patient, diagnosed with treatment-resistant schizophrenia, was started on clozapine, but 9 months later he presented with fever, cough, leukopenia, and neutropenia. Clozapine was discontinued, and empirical treatments with cefepime and filgrastim were initiated. Serum beta-D-glucan and Aspergillus galactomannan antigen tests were positive, and chest CT showed well-circumscribed nodules, leading to a probable diagnosis of IPA. Antifungal therapy was switched from micafungin to voriconazole according to guidelines. His neutropenia and fever improved, and he was re-transferred to a psychiatric hospital. Conclusion: CLIA can be complicated by fungal infections. When patients with CLIA present with fever, fungal infections, including IPA, should be considered in the differential diagnosis. Serological tests, including beta-D-glucan and Aspergillus galactomannan, are useful for the diagnosis of IPA as well as the appropriate use of antifungal agents in patients with CLIA. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1612-1872 2025 Antifouling Activity of Xylemin, Its Structural Analogs, and Related Polyamines e202403213 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takefumi Yorisue Institute of Natural and Environmental Sciences, University of Hyogo Kenta Tanaka Research Institute for Interdisciplinary Science, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Biofouling, which is the accumulation of organisms on undersea structures, poses significant global, social, and economic issues. Although organotin compounds were effective antifoulants since the 1960s, they were banned in 2008 due to their toxicity to marine life. Although tin-free alternatives have been developed, they also raise environmental concerns. This underscores the need for effective, nontoxic antifouling agents. We previously synthesized N-(4-aminobutyl)propylamine (xylemin) and its structural analogs. In this study, we assayed the antifouling activity and toxicity of xylemin, its structural analogs, and related polyamines toward cypris larvae of the barnacle Amphibalanus amphitrite. Xylemin and its Boc-protected analog exhibited antifouling activities with 50% effective concentrations (EC50) of 4.25 and 6.11 µg/mL, respectively. Four xylemin analogs did not show a settlement-inhibitory effect at a concentration of 50 µg/mL. Putrescine, spermidine, spermine, and thermospermine, which are xylemin-related polyamines, did not display antifoulant effects (EC50 > 50 µg/mL). All evaluated compounds were nontoxic at a concentration of 50 µg/mL. These findings indicate that the size and structure of the N-alkyl group are essential for the antifouling activity of xylemin. Therefore, xylemin and its analogs hold promise as nontoxic, eco-friendly antifouling agents, offering a sustainable solution to biofouling in marine environments. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1433-7851 64 8 2025 B,N‐Embedded Helical Nanographenes Showing an Ion‐Triggered Chiroptical Switching Function e202418546 EN Chihiro Maeda Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Sayaka Michishita Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Issa Yasutomo Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Tadashi Ema Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Intramolecular oxidative aromatic coupling of 3,6-bis(m-terphenyl-2’-yl)carbazole provided a bis(m-terphenyl)-fused carbazole, while that of 3,6-bis(m-terphenyl-2’-yl)-1,8-diphenylcarbazole afforded a bis(quaterphenyl)-fused carbazole. Borylation of the latter furnished a B,N-embedded helical nanographene binding a fluoride anion via a structural change from the three-coordinate boron to the four-coordinate boron. The anionic charge derived from the fluoride anion is stabilized over the expanded π-framework, which leads to the high binding constant (Ka) of 1×105 M−1. The four-coordinate boron species was converted back to the parent three-coordinate boron species with Ag+, and the chiroptical switch between the three-coordinate boron and four-coordinate boron species has been achieved via the ion recognition with the change in the color and glum values. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0361-8609 96 10 2021 Validated international definition of the thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly clinical subtype (TAFRO) of idiopathic multicentric Castleman disease 1241 1252 EN Yoshito Nishimura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences David C. Fajgenbaum Center for Cytokine Storm Treatment & Laboratory, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania Sheila K. Pierson Center for Cytokine Storm Treatment & Laboratory, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania Noriko Iwaki Hematology/Respiratory Medicine, Kanazawa University Graduate School of Medical Science Asami Nishikori Division of Pathophysiology, Okayama University Graduate School of Health Sciences Mitsuhiro Kawano Department of Rheumatology, Kanazawa University Graduate School of Medical Science Naoya Nakamura Department of Pathology, Tokai University School of Medicine Koji Izutsu Department of Hematology, National Cancer Center Hospital Kengo Takeuchi Department of Pathology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research Midori Filiz Nishimura Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuyuki Yoshizaki Department of Organic Fine Chemicals, Institute of Scientific and Industrial Research, Osaka University Eric Oksenhendler Department of Clinical Immunology, Hôpital Saint-Louis Frits van Rhee Myeloma Center, University of Arkansas for Medical Sciences Yasuharu Sato Division of Pathophysiology, Okayama University Graduate School of Health Sciences Thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly (TAFRO) syndrome is a heterogeneous entity manifesting with a constellation of symptoms described above that can occur in the context of idiopathic multicentric Castleman disease (iMCD) as well as infectious diseases, malignancies, and rheumatologic disorders. So, iMCD-TAFRO is an aggressive subtype of iMCD with TAFRO syndrome and often hyper-vascularized lymph nodes. Since we proposed diagnostic criteria of iMCD-TAFRO in 2016, we have accumulated new insights on the disorder and additional cases have been reported worldwide. In this systematic review and cohort analysis, we established and validated a definition for iMCD-TAFRO. First, we searched PubMed and Japan Medical Abstracts Society databases using the keyword “TAFRO” to extract cases. Patients with possible systemic autoimmune diseases and hematologic malignancies were excluded. Our search identified 54 cases from 50 articles. We classified cases into three categories: (1) iMCD-TAFRO (TAFRO syndrome with lymph node histopathology consistent with iMCD), (2) possible iMCD-TAFRO (TAFRO syndrome with no lymph node biopsy performed and no other co-morbidities), and (3) TAFRO without iMCD or other co-morbidities (TAFRO syndrome with lymph node histopathology not consistent with iMCD or other comorbidities). Based on the findings, we propose an international definition requiring four clinical criteria (thrombocytopenia, anasarca, fever/hyperinflammatory status, organomegaly), renal dysfunction or characteristic bone marrow findings, and lymph node features consistent with iMCD. The definition was validated with an external cohort (the ACCELERATE Natural History Registry). The present international definition will facilitate a more precise and comprehensive approach to the diagnosis of iMCD-TAFRO. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0309-0167 2025 Kikuchi‐Fujimoto disease: investigating comprehensive clinicopathological features and risk factors for recurrence EN Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Chikako Sakao Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yuka Kurokawa Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yoshito Nishimura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Hidetaka Yamamoto Department of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Aims: Kikuchi-Fujimoto disease (KFD) is a rare disease that typically manifests with fever and cervical lymphadenopathy. Little is known about the risk factors associated with recurrence and their correlation with clinicopathologic features. Methods and Results: We analysed 112 patients with KFD, predominantly female (61/112, 54.5%), with an average age of 29.4 years. The incidence was higher in males up to the age of 20 and higher in females from their 30s onwards. Of the 70 patients with follow-up data, 23% experienced recurrence. Recurrence was associated with lower C4 levels (P = 0.038) and higher antinuclear antibody (ANA) rates (P = 0.007) compared to transient disease. The mean duration of symptoms was 71.5 days. Lymph node histology in 98 cases (excluding 14 needle biopsy specimens) was classified into three patterns: proliferative (n = 75, 77%), necrotizing (n = 22, 22%), and xanthomatous (n = 1, 1%). The necrotizing pattern associated with significantly enlarged lymph nodes (P = 0.047) and a longer symptom duration (P = 0.009) than the proliferating pattern. The number of CD4-positive lymphocytes was significantly lower in the necrotizing type than in the proliferative type (P < 0.001). Conclusion: These results indicated that low C4 levels and positive ANA were associated with KFD recurrence. Although the aetiology of KFD remains elusive, given that some cases develop autoimmune disease, the results suggest that patients with recurrent KFD represent an intermediate status between those with transient KFD and those with overt autoimmune disease. The comprehensive clinicopathological findings of this study may be useful for elucidating its pathogenesis and predicting the clinical course. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0965-7576 2025 Wake Not a Sleeping Lion: Free Trade Agreements and Decision Rights in Multinationals EN Hiroshi Mukunoki Faculty of Economics, Gakushuin University Hirofumi Okoshi Faculty of Economics, Okayama University Free trade agreements with rules of origin affect the location of input production for vertically integrated multinational enterprises. The relocation induced by a free trade agreement changes the allocation of decision rights within multinational enterprises and the purpose of transfer pricing from avoiding high taxes to strengthening their product market competitiveness. This study shows that a free trade agreement with rules of origin may hurt both a multinational enterprise and a local firm, despite tariff elimination, when the relocation occurs and the decision rights change from centralization to decentralization. Moreover, such a free trade agreement can hurt consumers. Nevertheless, rules of origin increase the feasibility of free trade agreements due to larger tax revenues. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 13 2 2025 Crowned Dens Syndrome Triggered by Dental Treatment e70168 EN Satoru Morita Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yohei Masuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiaki Soejima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Crowned dens syndrome (CDS) is an important yet often overlooked cause of fever and neck pain, frequently leading to unnecessary examinations and treatments and misdiagnosis as infectious diseases or rheumatic diseases. The mechanism of an acute attack of CDS is not clarified completely, while it is considered that severe systemic stress can trigger inflammation caused by calcium pyrophosphate crystals. We describe a case of CDS triggered by localized physical stress to the neck and emphasize the importance of considering this condition in cases of fever and neck pain following dental treatment. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2769-2558 4 1 2025 Trends in uptake of cancer screening among people with severe mental illness before and after the COVID-19 pandemic in Japan: A repeated cross-sectional study e70062 EN Yuto Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masaki Fujiwara Department of Neuropsychiatry, Okayama University Hospital Naoki Nakaya Tohoku Medical Megabank Organization, Tohoku University Koji Otsuki Department of Psychiatry, Faculty of Medicine, Shimane University Taichi Shimazu Division of Behavioral Sciences, National Cancer Center Institute for Cancer Control, National Cancer Center Maiko Fujimori Division of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer Center Shiro Hinotsu Department of Biostatistics and Data Management, Sapporo Medical University Kiwamu Nagoshi Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University Yosuke Uchitomi Department of Cancer Survivorship and Digital Medicine, The Jikei University School of Medicine Masatoshi Inagaki Department of Psychiatry, Faculty of Medicine, Shimane University Aim: The aim of this study was to investigate trends in cancer screening participation among people with severe mental illness (PSMI) from periods before and after the COVID-19 pandemic. Methods: In this repeated cross-sectional study, we used anonymized datasets on municipal cancer screening participation among PSMI in Okayama City. The data covered fiscal year (FY) 2018 to FY2022; we used the municipal cancer screening database and Medical Payment for Services and Supports for Persons with Disabilities. PSMI were defined as those with schizophrenia or related psychotic disorders (F20-29) or bipolar disorder (F30 or F31), identified using International Classification of Diseases, Tenth Revision, codes. The analysis included men and women aged 40-69 years for colorectal and lung cancer screening; men and women aged 50-69 years for gastric cancer screening; women aged 40-69 years for breast cancer screening; and women aged 20-69 years for cervical cancer screening. Municipal cancer screening rates among PSMI were calculated for each FY. Results: For all cancer types, cancer screening rates for PSMI in FY2020 (colorectal: 9.0%; lung: 11.6%; gastric: 4.9%; breast: 6.2%; and cervical: 6.1%) were lower than the rates in FY2019 (11.5%, 14.0%, 6.5%, 9.3%, and 8.3%, respectively). In FY2022, the rates (9.9%, 12.9%; 5.3%; 8.0%, and 6.9%, respectively) recovered, but remained low. Conclusion: This study showed that cancer screening rates among PSMI were very low, both before and after the COVID-19 pandemic. Efforts to encourage participation in cancer screening in this population are urgently needed. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2692-4609 5 1 2025 Efficacy and safety of endoscopic ultrasonography-guided radiofrequency ablation of small pancreatic neuroendocrine neoplasms: A prospective, pilot study e70073 EN Kazuyuki Matsumoto 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 Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Hospital Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Hospital Kei Harada Department of Gastroenterology and Hepatology, Okayama University Hospital Nao Hattori Department of Gastroenterology and Hepatology, Okayama University Hospital Ryosuke Sato Department of Gastroenterology and Hepatology, Okayama University Hospital Taisuke Obata Department of Gastroenterology and Hepatology, Okayama University Hospital Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuya Yasui Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Hospital Ryo Harada Department of Gastroenterology, Japanese Red Cross Okayama Hospital Masakuni Fujii Department of Internal Medicine, Okayama Saiseikai General Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Objectives: Endoscopic ultrasonography (EUS)-guided radiofrequency ablation has recently been introduced as one of the management strategies for small pancreatic neuroendocrine neoplasms (PNENs). However, prospective data on its safety and efficacy remain limited. Methods: This prospective pilot study was conducted at Okayama University Hospital from May 2023 to December 2024. Patients with grade 1 PNENs <= 15 mm, confirmed by EUS-guided fine-needle aspiration, were included. The primary endpoint was safety (adverse events [AEs] evaluated according to the 2010 guidelines of the American Society for Gastrointestinal Endoscopy. Severe AEs were defined as moderate or higher in American Society for Gastrointestinal Endoscopy grading and grade >= 3. Secondary endpoints included efficacy (complete response on contrast-enhanced computed tomography at 1 and 6 months), treatment details, device failure, diabetes mellitus exacerbation, and overall survival at 6 months. Results: Five patients with non-functional PNENs (median age: 64 years; median tumor size: 10 mm) were treated. AEs occurred in two patients (40%, 2/5), although none was severe. Both patients developed asymptomatic pseudocysts, one experienced mild pancreatitis, and both resolved with conservative treatment. The complete response rates on contrast-enhanced computed tomography at one and 6 months were 100%. The median procedure time was 16 min without any device failure, and the median hospitalization was 5 days. None of the patients developed new-onset or worsening diabetes mellitus. The 6-month overall survival rate was 100%. Conclusion: EUS-guided radiofrequency ablation demonstrated a high complete response rate with no severe AEs in this pilot study, suggesting a minimally invasive option for small, low-grade PNENs (jRCTs062230014). No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2197-1153 12 1 2025 The use of lateral wedge insoles delays osteoarthritis progression and improves clinical outcomes in medial meniscus posterior root repair e70141 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 Purpose: The purpose of this retrospective study was to evaluate the efficacy of using a lateral wedge insole (LWI) during the first 3 months after medial meniscus posterior root (MMPR) repair. Methods: Overall, 179 patients were categorized into LWI use (LWI group, 90 patients) and nonuse (control group, 89 patients) groups. Patients in the LWI group were instructed to wear an LWI from the initiation of load bearing up to 3 months postoperatively. Medial meniscus extrusion (MME) was evaluated preoperatively and 1 year postoperatively, Kellgren–Lawrence (KL) grade and clinical scores were evaluated preoperatively and 2 years postoperatively, and second-look arthroscopic meniscal healing scores were evaluated at 1 year postoperatively. Results: The proportion of patients with KL grade progression at 2 years postoperatively was significantly lower in the LWI group than in the control group (23.3% vs. 39.3%; p = 0.024). Change in the MME at 1 year postoperatively was significantly smaller in the LWI group than in the control group (1.1 ± 1.2 vs. 1.6 ± 1.4 mm; p = 0.042). The Lysholm score (p = 0.003) and Knee Injury and Osteoarthritis Outcome Scores-sport and recreation function (p = 0.027) at 2 years postoperatively were significantly superior in the LWI group than in the control group. The arthroscopic meniscal healing score after 1 year was not significantly different between the LWI and control groups (total score, 7.6 ± 1.1 vs. 7.4 ± 1.3 points; p = 0.732). The anteroposterior width of the repaired posterior root at 1 year second-look evaluation was significantly broader in the LWI group than in the control group (7.7 ± 1.6 vs. 6.9 ± 1.6 mm; p = 0.001). Conclusions: The use of LWI is an effective way to delay postoperative osteoarthritis progression and improve clinical outcomes after MMPR repair. Level of Evidence: Level III. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2090-6447 2025 1 2025 A Case of an Oral Elastofibromatous Lesion: A Clinicopathological Analysis With a Literature Review 5556176 EN Sawako Ono Department of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masanori Masui Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital Kyoichi Obata Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoya Nakamura Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital Yoshihiko Furuki Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital Satoko Nakamura Department of Pathology, Kagawa Prefectural Central Hospital Hidetaka Yamamoto Department of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Elastofibromatous changes of the oral mucosa, such as an elastofibroma (EF) or an elastofibromatous lesion (EFL), are not well recognized, and the second such case in Japan is reported. A 72-year-old man wearing a complete maxillary denture presented with a small nodule on the hard palate. Histopathological examination showed abundant fibrous tissue with numerous elastic fibers on Elastica van Gieson (EvG) staining. The diagnosis of an oral EFL was made. In the review of oral EF and EFL, no cases with recurrence were identified, but such lesions may resemble neoplastic lesions macroscopically. Accurate diagnosis using EvG stain is needed to recognize oral EFs and EFLs. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 13 3 2025 Long-Term Follow-Up of a Patient With SPG11 198 200 EN Yosuke Osakada Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chika Matsuoka Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Fukui Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichiro Tsunoda Department of Neurology, Tsuyama Chuo Hospital Kentaro Deguchi Department of Neurology, Okayama City Hospital Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Ishiura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University We present a case of a male patient with disease-causing variants in SPG11, a causative gene for autosomal recessive spastic paraplegia with a thin corpus callosum (ARHSP-TCC), as well as juvenile amyotrophic lateral sclerosis (ALS5) and Charcot–Marie–Tooth disease (CMT2X). A neurological examination at age 18 revealed dysarthria, muscle weakness in bilateral lower extremities, hyperreflexia in patellar reflex, hyporeflexia in Achilles reflex with an extensor plantar reflex, and intellectual disability. Magnetic resonance imaging revealed a thin corpus callosum and ears of the lynx sign. At the age of 26, weakness and muscle atrophy progressed. While no sensory disturbances were noted, there was a mild decrease in sensory nerve action potentials of the sural nerve over the 8 years between 18 and 26. Clinicians should be aware that SPG11 belongs to the same spectrum of disorders as ALS5 and CMT2X and presents various phenotypes depending on the stage of the disease. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 13 1 2025 Undetermined Ruptured Low-Grade Appendiceal Mucinous Neoplasm Following High-Energy Blunt Abdominal Trauma Requiring Emergency Laparotomy e70071 EN Ippei Matsuo Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Akari Tsuji Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Ryo Tanabe Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Toshihisa Matsumura Department of Digestive Surgery, Japanese Red Cross Okayama Hospital Mikoto Shimabara Department of Digestive Surgery, Japanese Red Cross Okayama Hospital Masaaki Akai Department of Digestive Surgery, Japanese Red Cross Okayama Hospital Shoji Takagi Department of Digestive Surgery, Japanese Red Cross Okayama Hospital Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Blunt abdominal trauma causing intraperitoneal injury and/or bleeding can be life-threatening, requiring immediate intervention. Diagnosing these cases can be challenging, especially when pre-existing conditions are involved. Low-grade appendiceal mucinous neoplasm (LAMN) is a rare tumor of the appendix that can lead to pseudomyxoma peritonei. Herein, we present a case of ruptured LAMN following blunt abdominal trauma after a high-energy head-on collision, complicating the differentiation from other intraperitoneal injuries. A 42-year-old Japanese female was brought to our hospital following high-energy head-on collision. She presented with stable vital signs, complaining of anterior chest pain and abdominal tenderness without peritoneal irritation. Computed tomography scans indicated multiple fractures in her chest and complex fluid around the Douglas fossa extending to the ileocecal area, with a slightly dilated appendix tip. Despite stable vitals, emergency laparotomy was needed for suspected peritonitis and/or intraperitoneal hemorrhage. Emergency laparotomy revealed yellowish, jelly-like ascites and a ruptured appendiceal tumor. LAMN was suspected, and the appendix was completely resected, with cytoreductive surgery carefully performed. Histopathological examination confirmed the diagnosis of LAMN. Postoperative course was uneventful, and the patient was discharged on Day 13 and referred for further LAMN management. This case report highlights the diagnostic difficulties of LAMN rupture following blunt abdominal trauma, stressing the need to consider rare conditions like LAMN in differential diagnoses of acute abdomen posttrauma. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2574-173X 45 1 2025 Nicotine dependence based on the tobacco dependence screener among heated tobacco products users in Japan, 2022-2023: The JASTIS study e12512 EN Takuma Kitajima Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideyuki Kanda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Tabuchi Division of Epidemiology, Department of Health Informatics and Public Health, School of Public Health, Tohoku University Graduate School of Medicine Heated tobacco products (HTPs) are nicotine-containing products similar to cigarettes and are widely used in Japan. However, there has been insufficient research on nicotine dependence associated with HTP use. This study investigated the association of the types of individuals who smoked with the prevalence of nicotine dependence. We utilized data from the Japan Survey on Tobacco and Health (JASTIS). A total of 7969 participants who currently smokes was selected from the 2022 and 2023 survey respondents for the analysis. Nicotine dependence was defined as a score of 5 or higher on the Tobacco Dependence Screener (TDS). The prevalence of nicotine dependence was 43.0% (3473/8077) among all participants who smoked, 42.9% (1479/3447) among those who used cigarettes, 44.2% (760/1720) among those who used two products, and 43.0% (1206/2802) among those who used HTPs. The prevalence of nicotine dependence was statistically higher in the participants who used two products than in cigarettes (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.04-1.33). When classified by temperature, participants who used of two products (high-temp and low-temp) and those using participants who used HTPs (high-temp) had higher ORs for prevalent nicotine dependence (OR, 1.31 [95% CI, 1.14-1.51]) and (OR, 1.12 [95% CI, 1.00-1.25], respectively) compared to participants who used cigarettes. Additionally, the ORs for prevalent nicotine dependence increased with the number of tobacco sticks smoked per day. These results suggest that HTP use, particularly high-temperature HTPs use, and a higher number of tobacco sticks smoked is associated with nicotine dependence. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2052-8817 11 1 2024 Characteristics and outcomes of subarachnoid hemorrhage from vertebral artery dissection: A comparative study with other non-traumatic etiologies e70031 EN Shu Oshita Okayama University Medical School Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunta Jinno Department of Emergency, Critical Care, and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ippei Matsuo Department of Emergency, Critical Care, and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masafumi Hiramatsu Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Haruma Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenji Sugiu Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shota Tanaka Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aim: Vertebral artery dissection (VAD) is a rare cause of non-traumatic subarachnoid hemorrhage (SAH) with significant clinical implications. This study compared the clinical characteristics and outcomes of SAH from intracranial VAD rupture to those from other etiologies, primarily aneurysmal rupture. Methods: This single-center retrospective cohort study at Okayama University Hospital included patients with non-traumatic SAH diagnosed between 2019 and 2023. Patients were categorized into "VAD rupture" and "other etiologies" groups. The main outcome was clinical presentation and symptoms. Additional outcomes included ICU mortality, in-hospital mortality, and unfavorable outcomes at discharge and 6 months, defined as a modified Rankin Scale score of 3-6. Results: A total of 66 patients were included, with 14 in the VAD rupture group and 52 in the other etiologies group. The VAD rupture group was younger (median age 49 vs. 64 years, p = 0.003) and had a higher incidence of out-of-hospital cardiac arrest (42.9% vs. 9.6%, p = 0.011). Preceding headache was more common in the VAD rupture group (78.6% vs. 11.5%, p < 0.001), with a median duration of 36 h before presentation. ICU and in-hospital mortality was higher in the VAD rupture group (both 50.0% vs. 19.3%, p = 0.019). No significant differences were found in unfavorable neurological outcomes at hospital discharge and 6 months. Conclusions: VAD-related SAH often presents with prodromal headaches, severe symptoms like out-of-hospital cardiac arrest, and higher ICU and in-hospital mortality than other SAH causes, though long-term outcomes are similar. Larger, prospective studies are needed to refine interventions. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0022-3042 169 1 2024 Exploring the Role of Ccn3 in Type III Cell of Mice Taste Buds e16291 EN Kuanyu Wang Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihiro Mitoh Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kengo Horie Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryusuke Yoshida Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Different taste cells express unique cell-type markers, enabling researchers to distinguish them and study their functional differentiation. Using single-cell RNA-Seq of taste cells in mouse fungiform papillae, we found that Cellular Communication Network Factor 3 (Ccn3) was highly expressed in Type III taste cells but not in Type II taste cells. Ccn3 is a protein-coding gene involved in various biological processes, such as cell proliferation, angiogenesis, tumorigenesis, and wound healing. Therefore, in this study, we aimed to explore the expression and function of Ccn3 in mouse taste bud cells. Using reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry (IHC), we confirmed that Ccn3 was predominantly expressed in Type III taste cells. Through IHC, quantitative real-time RT-PCR, gustatory nerve recordings, and short-term lick tests, we observed that Ccn3 knockout (Ccn3-KO) mice did not exhibit any significant differences in the expression of taste cell markers and taste responses compared to wild-type controls. To explore the function of Ccn3 in taste cells, bioinformatics analyses were conducted and predicted possible roles of Ccn3 in tissue regeneration, perception of pain, protein secretion, and immune response. Among them, an immune function is the most plausible based on our experimental results. In summary, our study indicates that although Ccn3 is strongly expressed in Type III taste cells, its knockout did not influence the basic taste response, but bioinformatics provided valuable insights into the possible role of Ccn3 in taste buds and shed light on future research directions. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0947-6539 31 14 2025 Graphene Oxide as a Self‐Carbocatalyst to Facilitate the Ring‐Opening Polymerization of Glycidol for Efficient Polyglycerol Grafting e202404400 EN Yajuan Zou Research Institute for Interdisciplinary Science, Okayama University Kentaro Ohkura Graduate School of Natural Science and Technology, Okayama University Israel Ortiz‐Anaya Research Institute for Interdisciplinary Science, Okayama University Ryota Kimura Graduate School of Natural Science and Technology, Okayama University Alberto Bianco Research Institute for Interdisciplinary Science, Okayama University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Grafting carbon-based nanomaterials (CNMs) with polyglycerol (PG) improves their application potentials in biomedicine and electronics. Although “grafting from” method offers advantages over “grafting to” one in terms of operability and versatility, little is known about the reaction process of glycidol with the surface groups onto CNMs. By using graphene oxide (GO) as a multi-functional model material, we examined the reactivity of the surface groups on GO toward glycidol molecules via a set of model reactions. We reveal that carboxyl groups spontaneously react with the epoxide ring with no need of catalyst, while GO catalyzes the reactions of hydroxyl groups with the epoxide of glycidol. In addition, the hydroxyl group of glycidol can open the epoxide in the basal plane of GO. The subsequent polymerization of PG is supposed to propagate at the primary and/or the secondary hydroxyl groups, generating a ramified PG macromolecule with random branch-on-branch topology. In addition, ketones, benzyl esters and aromatic ethers are found not to react with glycidol even in the presence of GO, while the aldehydes are easily oxidized into carboxyl groups under ambient condition, behaving then as the carboxyl groups. Our findings pose the foundation for understanding the polymerization mechanism of PG on CNMs. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 13 1 2025 Eyelid Spindle Cell Lipoma: Case Report and Review of Three Patients in Literature e70097 EN Toshihiko Matsuo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kiyoshi Yamada Plastic and Reconstructive Surgery, Kousei Hospital Yasumasa Monobe Department of Pathology, General Medical Center, Kawasaki Medical School Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University A 39-year-old woman presented a saucer-shaped mass in the left upper eyelid and underwent the extirpation at local anesthesia. Pathologically, collagen fibers, capillaries, small vessels, and CD34-positive spindle cells were dispersed among mature adipose tissues, indicative of spindle cell lipoma. Long-lasting cyst-like eyelid masses would be usually dermoid cysts, and spindle cell lipoma would be listed as a rare pathological diagnosis in differential diagnoses of cyst-like lesions in the upper and lower eyelid. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1444-1586 25 1 2024 Effectiveness of oral health care intervention for stroke patients following the introduction of Oral Health Assessment Tool 48 53 EN Kazuyuki Matsunaga Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Ayaka Yoshida‐Tsuboi Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Ken Inohara Brain Attack Center, Ota Memorial Hospital Yasuko Yoshida Brain Attack Center, Ota Memorial Hospital Kanako Nakahama Brain Attack Center, Ota Memorial Hospital Kazuki Sasaki Brain Attack Center, Ota Memorial Hospital Fumie Souda Brain Attack Center, Ota Memorial Hospital Yuka Terasawa Brain Attack Center, Ota Memorial Hospital Yutaka Shimoe Brain Attack Center, Ota Memorial Hospital Kazu Takeuchi‐Hatanaka Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Tadashi Yamamoto The Center for Graduate Medical Education (Dental Division), Okayama University Hospital Kazuhiro Omori Department of Pathophysiology – Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsuo Kohriyama Brain Attack Center, Ota Memorial Hospital Shogo Takashiba Department of Pathophysiology – Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aim: This study aimed to evaluate the effectiveness of oral health assessment tools in facilitating oral health care interventions by dental care providers for acute stroke patients within 48 h of admission, following a reform of the nursing system. Methods: Data were gathered from a retrospective cohort study conducted at a stroke center, comparing 10 months before and after the implementation of the reformed system, with a 2-month interval. Parameters assessed included stroke type, severity measured using the National Institutes of Health Stroke Scale, stroke history, stroke-related factors, number of teeth, hospitalization cost and duration, occurrence of fever and pneumonia, stroke treatment, days from admission to dental intervention, and intervention frequency. Results: Implementation of the new system significantly reduced the time before dental intervention (P < 0.001), increased the frequency of interventions (P < 0.001), and allowed for the management of more severe cases (P = 0.007). However, there was a slight increase in the occurrence of fevers and the days of fever (P = 0.039 and P = 0.015, respectively). Multiple regression analysis showed that fever days were positively correlated with stroke severity and the number of days from admission to dental intervention (P < 0.001 and P = 0.013, respectively). Even after propensity score matching adjusting for stroke severity, these associations persisted. Additional multiple regression analysis was performed after this, but fever days were positively correlated with stroke severity and sex (P < 0.001 and P = 0.008, respectively), as well as with the presence of other factors affecting the occurrence of fever. Conclusions: Although the frequency and duration of fevers increased slightly, this approach, incorporating oral health assessment tools, made it possible to provide early dental intervention, particularly for patients with severe strokes. Geriatr Gerontol Int 2025; 25: 48–53. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1444-1586 25 1 2024 Impact of high blood pressure on the risk of mortality among Japanese people aged 65 years and older 82 89 EN Shinsuke Akagi Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soshi Takao Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Rumi Matsuo Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aim: The purpose of this study is to investigate the impact of abnormal blood pressure on the risk of all-cause and cardiovascular mortality in a large cohort of older Japanese people aged ≥65 years. Methods: This cohort study enrolled 54 760 participants from Okayama City aged ≥65 years who underwent basic health checkups from April 2006 to March 2008. Based on blood pressure, the participants were divided into six categories, from C1 (lowest) to C6 (highest). To assess the association of blood pressure with all-cause and cardiovascular mortality, we used survival analysis to estimate hazard ratios (HRs) for all-cause mortality and subdistribution HRs (SHRs) for cardiovascular mortality on C3. We then repeated the analyses based on age groups (65–74 years, 75–84 years, and ≥85 years). Results: The fully adjusted HRs for all-cause mortality, which included all individual potential confounders, were 1.11 (95% confidence interval [CI]: 1.04–1.19) for C5 and 1.23 (95% CI: 1.09–1.38) for C6, respectively. The fully adjusted SHRs for cardiovascular mortality were 1.11 (95% CI: 1.01–1.21) for C4, 1.19 (95% CI: 1.05–1.34) for C5, and 1.36 (95% CI: 1.09–1.70) for C6. In the age-stratification, an increased risk of hypotension was observed with older age. The HR for C1 was 1.28 (95% CI: 1.16–1.41) for ≥85 years. Conclusions: Hypertension increased the risk of all-cause and cardiovascular mortality among those aged 65–74 and 75–84 years, but not among those aged ≥85 years. Geriatr Gerontol Int 2024; ••: ••–••. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2193-5807 14 2 2024 Potassium tert-Butoxide-Mediated Ring-Opening of Indolines: Concise Synthesis of 2-Vinylanilines e202400552 EN Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shota Asai School of Pharmacy, Shujitsu University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University A concise and metal-free procedure has been developed for the synthesis of 2-vinylanilines. Reactions of indolines with tert-BuOK in DMSO afford the decorated 2-vinylanilines in yields up to 92 %. In addition, the 2, or 3-substituted indolines could be converted to trisubstituted alkenes. Also, the protocol can be scaled to afford gram quantities of the decorated 2-vinylanilines. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2045-7758 14 11 2024 Genomic Introgression in the Hybrid zones at the Margins of the Species' Range Between Ecologically Distinct Rubus Species e70476 EN Makiko Mimura Department of Biology, Okayama University Zhenxing Tang Department of Biology, Okayama University Shuji Shigenobu Trans-Omics Facility, National Institute of Basic Biology Katsushi Yamaguchi Trans-Omics Facility, National Institute of Basic Biology Tetsukazu Yahara Kyushu Open University Populations in extreme environments at the margins of a species' range are often the most vulnerable to climate change, but they may also experience novel evolutionary processes, such as secondary contact and hybridization with their relatives. The range overlap resulting from secondary contact with related species that have adapted to different climatic zones may act as corridors for adaptive introgression. To test this hypothesis, we examined the hybrid zones along the altitude of two closely related Rubus species, one temperate and the other subtropical species, at their southern and northern limits on Yakushima Island, Japan. Genomic cline analysis revealed non-neutral introgression throughout the genome in both directions in the two species. Some of these genomic regions involve gene ontology terms related to the regulation of several biological processes. Our niche modeling suggests that, assuming niche conservatism, the temperate species are likely to lose their suitable habitat, and the backcrossed hybrids with the subtropical species are already expanding upslope on the island. Adaptive introgression through the hybrid zone may contribute to the persistence and expansion of the species in the southernmost and northernmost populations. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2045-7634 13 20 2024 New Anti-Angiogenic Therapy for Glioblastoma With the Anti-Depressant Sertraline e70288 EN Nobushige Tsuboi 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 Atsuhito Uneda 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 Yasuki Suruga Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuji Matsumoto Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atsushi Fujimura Neutron Therapy Research Center, Okayama University Kentaro Fujii Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hideki Matsui Neutron Therapy Research Center, Okayama University Kazuhiko Kurozumi Department of Neurosurgery, Hamamatsu University School of Medicine Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Michiue Neutron Therapy Research Center, Okayama University Background and Aims: Anti-angiogenic therapies prolong patient survival in some malignancies but not glioblastoma. We focused on the relationship between the differentiation of glioma stem like cells (GSCs) into tumor derived endothelial cells (TDECs) and, anti-angiogenic therapy resistance. Especially we aimed to elucidate the mechanisms of drug resistance of TDECs to anti-angiogenic inhibitors and identify novel anti-angiogenic drugs with clinical applications. Results: The mouse GSCs, 005, were differentiated into TDECs under hypoxic conditions, and TDECs had endothelial cell characteristics independent of the vascular endothelial growth factor (VEGF) pathway. In vivo, inhibition of the VEGF pathway had no anti-tumor effect and increased the percentage of TDECs in the 005 mouse model. Novel anti-angiogenic drugs for glioblastoma were evaluated using a tube formation assay and a drug repositioning strategy with existing blood-brain barrier permeable drugs. Drug screening revealed that the antidepressant sertraline inhibited tube formation of TDECs. Sertraline was administered to differentiated TDECs in vitro and 005 mouse models in vivo to evaluate genetic changes by RNA-Seq and tumor regression effects by immunohistochemistry and MRI. Sertraline reduced Lama4 and Ang2 expressions of TDEC, which play an important role in non-VEGF-mediated angiogenesis in tumors. The combination of a VEGF receptor inhibitor axitinib, and sertraline improved survival and reduced tumor growth in the 005 mouse model. Conclusion: Collectively, our findings showed the diversity of tumor vascular endothelial cells across VEGF and non-VEGF pathways led to anti-angiogenic resistance. The combination of axitinib and sertraline can represent an effective anti-angiogenic therapy for glioblastoma with safe, low cost, and fast availability. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Delayed diagnostic interval and survival outcomes in pediatric leukemia: A single-center, retrospective study EN Kosuke TAMEFUSA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Trans men can achieve adequate muscular development through low-dose testosterone therapy: A long-term study on body composition changes EN Yusuke TOMINAGA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Radiological characteristics of skeletal growth in neonates and infants with achondroplasia EN Daisuke MIYAHARA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0947-6539 30 70 2024 MoSe2-Sensitized Water Splitting Assisted by C60-Dendrons on the Basal Surface e202402690 EN Tomoyuki Tajima Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tomoki Matsuura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Arif Efendi Department of Materials Design and Engineering, University of Toyama Mariko Yukimoto Department of Materials Design and Engineering, University of Toyama Yutaka Takaguchi Department of Materials Design and Engineering, University of Toyama To facilitate water splitting using MoSe2 as a light absorber, we fabricated water-dispersible MoSe2/C60-dendron nanohybrids via physical modification of the basal plane of MoSe2. Upon photoirradiation, the mixed-dimension MoSe2/C60 (2D/0D) heterojunction generates a charge-separated state (MoSe2⋅+/C60⋅−) through electron extraction from the exciton in MoSe2 to C60. This process is followed by the hydrogen evolution reaction (HER) from water in the presence of a sacrificial donor (1-benzyl-1,4-dihydronicotinamide) and co-catalyst (Pt-PVP). The apparent quantum yields of the HER were estimated to be 0.06 % and 0.27 % upon photoexcitation at the A- and B-exciton absorption peaks (λmax=800 and 700 nm), respectively. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2047-9980 13 22 2024 Eight-Year Outcomes of Cardiosphere-Derived Cells in Single Ventricle Congenital Heart Disease e038137 EN Kenta Hirai Department of Pediatrics Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryusuke Sawada Department of Pharmacology Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohiro Hayashi Department of Pediatrics Kurashiki Central Hospital Toru Araki Department of Pediatrics National Hospital Organization Fukuyama Medical Center Naomi Nakagawa Department of Pediatric Cardiology Hiroshima City Hiroshima Citizens Hospital Maiko Kondo Department of Pediatrics Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenji Yasuda Department of Pediatrics Shimane University Faculty of Medicine Takuya Hirata Department of Pediatrics Kyoto University Graduate School of Medicine Tomoyuki Sato Department of Pediatrics Jichi Medical University Yuki Nakatsuka Department of Data Science, Center for Innovative Clinical Medicine Okayama University Hospital Michihiro Yoshida Department of Data Science, Center for Innovative Clinical Medicine Okayama University Hospital Shingo Kasahara Department of Cardiovascular Surgery Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenji Baba Department of Pediatrics Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hidemasa Oh Department of Regenerative Medicine, Center for Innovative Clinical Medicine Okayama University Hospital the TICAP/PERSEUS Study Group Background: Cardiosphere‐derived cell (CDC) infusion was associated with better clinical outcomes at 2 years in patients with single ventricle heart disease. The current study investigates time‐to‐event outcomes at 8 years. Methods and Results: This cohort enrolled patients with single ventricles who underwent stage 2 or stage 3 palliation from January 2011 to January 2015 at 8 centers in Japan. The primary outcomes were time‐dependent CDC treatment effects on death and late complications during 8 years of follow‐up, assessed by restricted mean survival time. Among 93 patients enrolled (mean age, 2.3±1.3 years; 56% men), 40 received CDC infusion. Overall survival for CDC‐treated versus control patients did not differ at 8 years (hazard ratio [HR], 0.60 [95% CI, 0.21–1.77]; P=0.35). Treatment effect had nonproportional hazards for death favoring CDCs at 4 years (restricted mean survival time difference +0.33 years [95% CI, 0.01–0.66]; P=0.043). In patients with heart failure with reduced ejection fraction, CDC treatment effect on survival was greater over 8 years (restricted mean survival time difference +1.58 years [95% CI, 0.05–3.12]; P=0.043). Compared with control participants, CDC‐treated patients showed lower incidences of late failure (HR, 0.45 [95% CI, 0.21–0.93]; P=0.027) and adverse events (subdistribution HR, 0.50 [95% CI, 0.27–0.94]; P=0.036) at 8 years. Conclusions: By 8 years, CDC infusion was associated with lower hazards of late failure and adverse events in single ventricle heart disease. CDC treatment effect on survival was notable by 4 years and showed a durable clinical benefit in patients with heart failure with reduced ejection fraction over 8 years. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01273857 and NCT01829750. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2090-6447 2024 2024 A Rare Case of Multiple Myeloma Identified Following the Diagnosis of Amyloidosis of the Tongue 8836103 EN Hideka Kanemoto Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kyoichi Obata Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichi Kadoya Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kisho Ono Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hotaka Kawai Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Kunisada Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mayumi Yao Department of Oral and Maxillofacial Surgery, Tsuyama Chuo Hospital Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Amyloidosis is a disease in which amyloid protein is deposited in organs and tissues, resulting in functional impairment. Amyloidosis occurs in 12%-30% of patients with multiple myeloma, but in rare cases, amyloidosis may precede the diagnosis of multiple myeloma. Our patient was a 76-year-old Japanese male on dialysis. Multiple nodules accompanied by ulcers were observed on his tongue. He had no subjective symptoms or clinical findings associated with multiple myeloma. The histopathological findings suggested amyloidosis. We suspected both systemic and localized amyloidosis and performed a comprehensive systemic examination. Since the patient had been on dialysis for only a short period of time (similar to 3 months), dialysis-related amyloidosis was ruled out. After blood and urine tests, a diagnosis of multiple myeloma was made. Chemotherapy treatment was started, but the patient's multiple myeloma could not be suppressed and the tongue amyloidosis worsened, leading to his death 2 years and 2 months after the initial diagnosis. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1862-832X 19 1 2024 Structural Evolution of Microgels During Precipitation Polymerization Revealed by Light Scattering and Electrophoresis 2400024 EN Yuji Sato Graduate School of Environmental Life, Natural Sciences and Technology, Okayama University Ryuji Namioka Graduate School of Textile Science & Technology, Shinshu Universit Yuichiro Nishizawa Graduate School of Environmental Life, Natural Sciences and Technology, Okayama University Daisuke Suzuki Graduate School of Environmental Life, Natural Sciences and Technology, Okayama University While precipitation polymerization allows the synthesis of microgels with controlled functional-group distributions, the structural development of these microgels during the polymerization process still remains unclear. In this study, microgels with different reactivity ratios between the monomer and charged co-monomer are prepared by precipitation polymerization, and the evolution of their size, thermoresponsive behavior, and surface properties during polymerization are evaluated. In particular, the surface properties of the microgels are analyzed quantitatively using the softness parameter and the surface charge density is calculated using Ohshima's equation. The results allowed describing the structural changes of microgels during precipitation polymerization well and provided design guidelines for functional microgels with controlled functional group distributions. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0815-9319 39 12 2024 Rates and risk factors of bleeding after gastric endoscopic submucosal dissection with continuous warfarin or 1‐day withdrawal of direct oral anticoagulants 2760 2766 EN Shoichiro Hirata Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenta Hamada Department of Practical Gastrointestinal Endoscopy, Okayama University Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Mouri Department of Gastroenterology and Hepatology, Kurashiki Central Hospital Koji Miyahara Department of Internal Medicine, Hiroshima City Hospital Takao Tsuzuki Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital Kenji Yamauchi Department of Gastroenterology, Mitoyo General Hospital Sayo Kobayashi Department of Internal Medicine, Fukuyama City Hospital Sakuma Takahashi Department of Gastroenterology, Kagawa Prefectural Central Hospital Ryuta Takenaka Department of Internal Medicine, Tsuyama Chuo Hospital Shinichiro Hori Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital Masafumi Inoue Department of Gastroenterology, Japanese Red Cross Okayama Hospital Tatsuya Toyokawa Department of Gastroenterology, National Hospital Organization Fukuyama Medical Center Mamoru Nishimura Department of Internal Medicine, Okayama City Hospital Shuhei Ishiyama Department of Internal Medicine, Okayama Saiseikai General Hospital Jiro Miyaike Department of Internal Medicine, Saiseikai Imabari Hospital Ryo Kato Department of Gastroenterology, National Hospital Organization Iwakuni Clinical Center Minoru Matsubara Department of Internal Medicine, Sumitomo Besshi Hospital Naoko Yunoki Department of Internal Medicine, Akaiwa Medical Association Hospital Hiromitsu Kanzaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, Okayama University Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideki Ishikawa Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Gut Study Group Background and Aim: The 2017 Japanese guidelines recommend continuing warfarin therapy during the perioperative period or discontinuing direct oral anticoagulants (DOACs) only on the day of endoscopic submucosal dissection for early gastric cancer. However, their safety has not been sufficiently explored. This study aimed to validate this management method. Methods: This retrospective, multicenter study analyzed the characteristics and outcomes of patients who underwent gastric endoscopic submucosal dissection between July 2017 and June 2019. The patients were categorized according to the use of warfarin or DOACs. Results: Among the 62 eligible patients, 53 (85%) were male (median age, 76 years). Warfarin was used in 10 patients (16%) and DOACs in 52 patients (84%). Fourteen patients taking DOACs (27%) used concomitant antiplatelet agents, with seven patients (13%) continuing treatment at the time of the endoscopic procedure. No postprocedural bleeding occurred in patients receiving warfarin (0%), whereas 10 cases (19%) of bleeding occurred in patients receiving DOACs: rivaroxaban, 0% (0/22); dabigatran, 0% (0/2); edoxaban, 43% (6/14); and apixaban, 29% (4/14). The type of anticoagulant (P < 0.01) and continuation of antiplatelet therapy (P = 0.02) were risk factors for postprocedural bleeding in patients receiving DOACs. Intraprocedural bleeding requiring transfusion or symptomatic thromboembolic events were not reported. Conclusions: Continuous warfarin therapy is preferred. DOAC withdrawal 1 day before a procedure is associated with a high bleeding rate, which may differ for different types of anticoagulants. The continuation of antiplatelet medications in patients receiving DOACs carries a high risk of bleeding and is a future challenge. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2040-1116 16 1 2024 Noncoding RNAs and diabetic kidney disease 8 9 EN Jun Wada Department of Nephrology,Rheumatology, Endocrinology andMetabolism, Okayama UniversityGraduate School of Medicine, Dentistryand Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1022-1336 46 1 2024 Elastomer Particle Monolayers Formed by the Compression of Poly(methyl acrylate) Microparticles at an Air/Water Interface 2400604 EN Yuma Sasaki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuichiro Nishizawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Natsuki Watanabe Department of Physics, Nagoya University Takayuki Uchihashi Department of Physics, Nagoya University Daisuke Suzuki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University In the previous study (Green Chem., 2023, 25, 3418), highly stretchable and mechanically tough poly(methyl acrylate) (pMA) microparticle-based elastomers can be formed by drying a microparticle-containing aqueous dispersion. This discovery has the potential to overcome the mechanical weakness of industrially produced aqueous latex films. However, in 3D-arranged particle films, structural complexity, such as the existence of defects, makes it difficult to clearly understand the relationship between the particle film structure and its mechanical properties. In this study, 2D-ordered pMA particle monolayers at the air/water interface of a Langmuir trough are prepared. Under high compression at the air/water interface, the microparticles contact their neighboring particles, and the resulting monolayers can be successfully transferred onto a solid substrate. The compression of the monolayer films is linked to an increase in the elastic modulus of the monolayer film on the solid substrate as evident from the local Young's modulus mapping using atomic force microscopy. Thus, pMA particle films with different mechanical properties can be created using a Langmuir trough. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2769-2558 2 2 2023 Effectiveness of psychological first aid in infectious disease pandemics: An overview of systematic reviews e107 EN Masahide Koda Co‐Learning Community Healthcare Re‐Innovation Office, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Horinouchi Department of Psychiatry, Hokkaido University Graduate School of Medicine Nozomu Oya Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Morio Aki Department of Psychiatry, Graduate School of Medicine, Kyoto University Akihisa Iriki Osaka Psychiatric Medical Center Kazufumi Yoshida Department of Health Promotion and Human Behavior, Graduate School of Medicine/School of Public Health, Kyoto University Yusuke Ogawa Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University Hironori Kuga National Center for Cognitive Behavior Therapy and Research, National Center of Neurology and Psychiatry Tomohiro Nakao Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University There is insufficient research on the usefulness of psychological interventions, such as psychological first aid (PFA), during outbreaks. We searched for and critically appraised systematic reviews that examined the effectiveness of PFA during infectious disease outbreaks, such as the novel coronavirus disease (COVID-19). Systematic reviews that examined the efficacy of PFA in the severe acute respiratory syndrome, Middle East respiratory syndrome coronavirus, Ebola virus disease, and COVID-19 outbreaks were searched through PubMed on February 19, 2021. The three included systematic reviews were critically appraised and assessed using AMSTAR-2. One review's overall confidence in its findings was evaluated as “high,” which suggested that PFA training had a favorable effect on healthcare personnel. Furthermore, the review also demonstrated that PFA was commonly used during outbreaks and could be delivered through multiple methods, such as a phone or video call. Although it was anticipated that PFA would improve subjective well-being, reports showed no evidence of reduced depression or insomnia. Future studies should examine additional numbers of PFA recipients and conduct quasi-experimental studies to better understand the effectiveness of PFA. Evidence on its effectiveness in infectious disease outbreaks is still lacking, along with research and evaluation methods. Quasi-experimental studies, such as comparisons with other psychological interventions, are required to better understand the effectiveness of PFA. No potential conflict of interest relevant to this article was reported.