Informa UK Limited Acta Medica Okayama 0020-739X 2026 Triangulation in teaching probability: teaching materials for the theoretical foundations of probability in real-world applications EN Yusuke Uegatani Hiroshima University High School Ippo Ishibashi Faculty of Education, Okayama University Aya Sakota Hiroshima University High School This paper proposes using the concept of triangulation with probabilistic models as a means to enhance theoretical inversion for deepening students’ understanding of the nature of probability in real-world contexts. Triangulation refers to the combined application of multiple methodologies to investigate the same phenomenon, particularly in the social sciences. Theoretical inversion refers to a shift in focus from surprising outcomes to the theoretical foundations of probability. The paper introduces three types of problem-solving tasks designed to enhance one of four types of triangulations: theory triangulation. Theoretical inversion is expected to emerge through engaging in these tasks. The characteristics of the problems are as follows. Problem 1 promotes students to compare different probabilistic models of events under similar procedures. Problem 2 provides students with an opportunity to simplify an experiment by omitting steps that add no new information. Problem 3 enhances students’ ability to recognise how subtle differences in the experimental setup can affect the resulting probability. These tasks are designed to encourage students to view probabilistic reasoning as a form of modelling and to appreciate the importance of assumptions, definitions of elementary events, and clarity in procedural descriptions. No potential conflict of interest relevant to this article was reported.

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 49 2 2026 Functional Transport Properties of Human Zinc Transporter 1: Kinetics and pH-Dependency 364 370 EN Yuma Yoshioka Department of Molecular Membrane Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takaaki Miyaji Department of Molecular Membrane Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Intracellular zinc (Zn2+) homeostasis is essential for physiological and pathological processes and is strictly regulated by Zn2+ transporters. Zinc transporter 1 (ZnT1) is a ubiquitously expressed plasma membrane-localized Zn transporter that exports Zn2+ from the cytoplasm to the extracellular space. However, the functional transport properties regarding kinetics and driving forces of ZnT1 remain debatable. In this study, we established a cell-free proteoliposome assay system and demonstrated that ZnT1 transports Zn2+ with high affinity in pH-dependent and pH-independent manners. The Km and Vmax of pH-dependent Zn2+ transport were 0.40 μM and 15.13 nmol/min/mg protein, and those of pH-independent Zn2+ transport were 0.52 μM and 8.88 nmol/min/mg protein (low concentrations of Zn2+), 3.02 μM and 17.59 nmol/min/mg protein (high concentrations of Zn2+), respectively, suggesting biphasic kinetic components of Zn2+ transport. Even without pH gradient formation, ZnT1 exhibits potent Zn2+ transport activity. In pH dependency, Zn2+ transport activity was higher at an inside pH of 6.0 than at 6.5–7.5 for proteoliposomes, despite the same ΔpH of 0.5–1.5. The Zn2+ transport activity decreased at an outside pH of 8.0, despite an increase in ΔpH. Although previous studies have proposed that ZnT1-mediated Zn2+ transport activity is driven by a calcium (Ca2+) gradient and not by a pH gradient, Ca2+ does not enhance Zn2+ transport activity in the presence or absence of a pH gradient. These results strongly suggest that ZnT1 protein transports Zn2+ optimally at a specific pH and exports excess intracellular Zn2+ even without ΔpH. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 2211-7156 25 2026 Peptide nanomicelles for NIR light-dependent siRNA delivery 103265 EN Taufik Fatwa Nur Hakim Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mizuki Kitamatsu Department of Applied Chemistry, Kindai University Shoumu Fujimoto Department of Applied Chemistry, Kindai University Kazunori Watanabe Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takashi Ohtsuki Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University The peptide amphiphile PA8, derived from the GAVILRR peptide, was developed as a carrier for small interfering RNA (siRNA) delivery; however, its RNA interference (RNAi) efficacy was limited owing to predominant endocytotic uptake. In this study, the RNAi efficiency of PA8 nanomicelle/siRNA complexes was enhanced by modifying the nanomicelles with the photosensitizer DY750 and the tumor-homing peptide iRGD. The conjugation of DY750 to the nanomicelles facilitated endosomal escape of the nanomicelle/siRNA complexes, enabling the cytosolic release of siRNA. Additionally, the incorporation of iRGD improved RNAi delivery efficiency in the AsPC-1 pancreatic ductal adenocarcinoma cell line. PA8-DY750-iRGD nanomicelle complexes loaded with siRNA against polo-like kinase 1 (PLK1) achieved an 80% reduction in PLK1 mRNA levels in AsPC-1 cells and a moderate 28% knockdown in NCI-N87 gastric cancer cells. Notably, no RNAi effect was observed in noncancerous 1C3D3 pancreatic cells or HEK293T kidney cells, underscoring the selectivity of this system for AsPC-1 cells. These findings highlight the potential of PA8-DY750-iRGD nanomicelle complexes as a targeted therapeutic platform for specific cancers, particularly pancreatic cancer. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Liquid–liquid phase separation by caged coacervating peptides 10464 EN Akinari Bando Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mizuki Kitamatsu Department of Applied Chemistry, Kindai University Yuuki Kanazaki Department of Applied Chemistry, Kindai University Rika Tojo Department of Applied Chemistry, Kindai University Kazunori Watanabe Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takashi Ohtsuki Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Liquid–liquid phase separation is an important biomolecular process in the formation of membraneless intracellular organelles that has inspired the development of artificial droplet systems. We developed caged coacervating peptides (CCPs) based on a histidine-rich squid beak protein sequence. The peptides were caged with a photodeprotectable (7-diethylaminocoumarin-4-yl)methoxycarbonyl group. The CCPs formed coacervates in the caged state and were partially dispersed upon blue-light irradiation. Photo-uncaging occurred rapidly, inducing coacervate dispersion. A mutant CCP with reduced π–π interactions exhibited efficient photo-dependent disassembly and enabled the encapsulation and release of a fluorescently labeled adenosine 5′-triphosphate (Bodipy-ATP) upon irradiation. These CCPs offer an efficient light-controlled approach for biomolecular encapsulation within coacervates and targeted drug delivery. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1472-6831 26 1 2026 Evaluation of contact-active antibacterial properties of cetylpyridinium chloride–graphene oxide coatings on dental restorative and titanium surfaces: an in vitro study 558 EN Keisuke Okubo Department of Periodontics and Endodontics, Field of Medical Development, Okayama University Gen Kano Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masato Komoda Research Institute for Interdisciplinary Science, Okayama University Hideyuki Kamata Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin Nakamura Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Shinoda-Ito Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Omori Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Shogo Takashiba Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objective Biofilm formation on dental restorative materials and implant surfaces plays a central role in the development of dental caries, periodontal disease, and peri-implantitis. Durable antimicrobial surface treatments that inhibit bacterial adhesion and biofilm formation remain a significant unmet need in restorative and implant dentistry. Therefore, this study aimed to develop a composite coating combining cetylpyridinium chloride and graphene oxide, and to evaluate its durable antibacterial surface modification under in vitro conditions.<br> Methods A composite coating consisting of cetylpyridinium chloride and graphene oxide was prepared and applied to composite resin and titanium surfaces. Antibacterial activity against Streptococcus mutans and Porphyromonas gingivalis was evaluated using adenosine triphosphate assays and fluorescence-based live/dead staining. Coating retention after washing and air-drying was assessed by optical microscopy and Raman spectroscopy.<br> Results Cetylpyridinium chloride-graphene oxide-coated surfaces showed a significant reduction in bacterial viability compared with phosphate-buffered saline, ethanol, and cetylpyridinium chloride-only controls. Antibacterial effects were maintained after rinsing and air-drying on both composite resin and titanium surfaces. Raman spectroscopy confirmed the persistence of characteristic graphene oxide bands after washing, indicating stable retention of the coating on the material surfaces.<br> Conclusions Cetylpyridinium chloride–graphene oxide coatings demonstrate sustained surface-associated antibacterial activity against key cariogenic and periodontal pathogens and remain stably adhered to common dental restorative and implant materials after washing. These findings suggest that cetylpyridinium chloride–graphene oxide coatings may serve as a durable contact-active surface modification strategy to reduce biofilm formation associated with dental caries and peri-implantitis. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 2 2026 Porphyromonas gingivalis Vesicles Control Osteoclast–Macrophage Lineage Fate 831 EN Elizabeth Leon Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Shin Nakamura Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Satoru Shindo Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Maria Rita Pastore Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Tomoki Kumagai Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Alireza Heidari Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Elaheh Dalir Abdolahinia Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Tomoya Ueda Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Takumi Memida Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Ana Duran-Pinedo Department of Oral Biology, College of Dentistry, University of Florida Jorge Frias-Lopez Department of Oral Biology, College of Dentistry, University of Florida Xiaozhe Han Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Xin Chen Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Shengyuan Huang Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Guoqin Cao Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Sunniva Ruiz Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Jan Potempa Department of Oral Immunology and Infectious Diseases, School of Dentistry, University of Louisville Toshihisa Kawai Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA Porphyromonas gingivalis (Pg), a keystone pathogen of chronic periodontitis, releases outer membrane vesicles (OMVs) that act as nanoscale vehicles to disseminate virulence factors within periodontal tissues and systemically beyond the oral cavity. Although Pg-OMVs are increasingly recognized as critical mediators of host–pathogen interactions, their effects on the differentiation and function of monocyte–macrophage/osteoclast lineage cells remain unclear. Here, we examined the impact of Pg-OMVs on the differentiation of RAW264.7 monocyte/macrophage-like cells into osteoclasts (OC) and/or macrophages (MΦ) in the presence of receptor activator of nuclear factor-κB ligand (RANKL). OMVs were isolated from Pg W83 and applied to RANKL-primed RAW264.7 cells using three distinct stimulation schedules: (1) simultaneous treatment with Pg-OMVs and RANKL at Day 0; (2) RANKL priming at Day 0 followed by Pg-OMV stimulation at Day 1; and (3) RANKL priming at Day 0 followed by Pg-OMV stimulation at Day 3. In all schedules, cells were cultured for 7 days from the initial RANKL exposure. Remarkably, simultaneous exposure to Pg-OMVs and RANKL (Schedule 1) markedly suppressed osteoclastogenesis (OC-genesis) while promoting M1 macrophage polarization. In contrast, delayed Pg-OMV stimulation of RANKL-primed cells (Schedules 2 and 3) significantly enhanced OC-genesis while reducing M1 polarization. These schedule-dependent effects were consistent with altered expression of osteoclastogenic markers, including dc-stamp, oc-stamp, nfatc1, and acp5. Importantly, a monoclonal antibody against OC-STAMP counteracted the Pg-OMV-induced upregulation of OC-genesis in Schedules 2 and 3. Furthermore, levels of Pg-OMV phagocytosis were inversely correlated with osteoclast formation. Finally, co-stimulation with RANKL and Pg-OMVs (Schedule 1) enhanced macrophage migratory capacity, whereas delayed stimulation with Pg-OMVs (Schedules 2 and 3) did not. Collectively, these findings indicate that Pg-OMVs exert stage-specific effects on the OC/MΦ lineage: stimulation at early stages of RANKL priming suppresses OC-genesis and promotes M1 polarization, whereas stimulation at later stages enhances OC-genesis without inducing M1 differentiation. Thus, Pg-OMVs may critically influence the fate of the OC/MΦ unit in periodontal lesions, contributing to disease progression and tissue destruction. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 7 2026 CXCR2-Dependent Infiltration of Tumor-Associated Neutrophils Is Linked to Enhanced CD8+ T Cell Effector Function and Reduced Lung Metastasis in 4T1 Breast Cancer 3143 EN Tiantian Li Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miao Tian Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Gakushi Nishida Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chunning Li Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Triple-negative breast cancer (TNBC) is characterized by prominent neutrophil infiltration; however, its significance remains controversial. Here, we investigated the role of neutrophil chemoattractant receptors in TNBC progression and metastasis. In contrast to wild-type (WT), Fpr1−/−, and Fpr2−/− mice, neutrophils were almost completely absent in 4T1 tumors from Cxcr2−/− mice, indicating a dominant role for CXCR2 in the recruitment of tumor-associated neutrophils, leading us to use Cxcr2−/− mice for further studies. Primary tumor growth was comparable between WT and Cxcr2−/− mice, whereas lung metastasis was significantly increased in Cxcr2−/− mice, with reduced expression of inflammatory cytokines, chemokines and cytotoxic molecules, including granzyme B and perforin, in primary tumors and metastatic lungs of Cxcr2−/− mice. In vitro, WT, but not Cxcr2−/−, neutrophils enhanced CD8+ T cell activation, partly via ICAM-1, and directly induced tumor cell death, supporting their anti-tumor function. To assess clinical relevance, transcriptomic data were analyzed. High neutrophil infiltration combined with elevated CXCR2 expression, and to a lesser extent CXCR1 expression, was associated with improved prognosis in patients with basal-like BC that largely overlaps with TNBC. Collectively, these findings suggest that CXCR2-mediated neutrophil recruitment exerts protective, anti-tumor effects and may represent a new prognostic marker for TNBC patients. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2662-4435 7 1 2026 Stability and distribution of dense hydrous magnesium silicates in the mantle transition zone under low water activity conditions 265 EN Yunke Song Key Laboratory of High-temperature and High-pressure Study of the Earth’s Interior, Institute of Geochemistry, Chinese Academy of Sciences Xinzhuan Guo State Key Laboratory of Critical Mineral Research and Exploration, Institute of Geochemistry, Chinese Academy of Sciences Kuan Zhai Key Laboratory of High-temperature and High-pressure Study of the Earth’s Interior, Institute of Geochemistry, Chinese Academy of Sciences Wei Guo State Key Laboratory of Geomicrobiology and Environmental Changes, School of Earth Sciences, China University of Geosciences (Wuhan) Takashi Yoshino Institute for Planetary Materials, Okayama University Water plays a central role in controlling the physical and chemical properties of Earth’s deep interior. It remains uncertain how water is stored in subducting slabs within the mantle transition zone, between depths of about 410 and 660 kilometers, and whether dense hydrous magnesium silicates act as major water carriers to greater depths. Here we report high-pressure and high-temperature laboratory experiments on the Mg-Si-H system at pressures of 16 and 21.5 GPa and a temperature of 1400 K to evaluate hydrous phase stability under transition zone conditions. We find that when bulk water content is below 1.22 wt%, H2O is predominantly incorporated into wadsleyite and ringwoodite rather than forming dense hydrous magnesium silicates. Because estimated water contents in subducted oceanic slabs are typically lower than one weight percent, formation of these silicates is unlikely, suggesting that the mantle transition zone may restrict large scale water transport into the lower mantle. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1470-1626 171 2 2026 Rho kinase and RND3 regulate the direct effect of estradiol-17β on oviductal tonus xaag004 EN Sayaka Kubota Laboratory of Reproductive Physiology, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Risa Okawara School of Agriculture, Okayama University Kohei Kawano Laboratory of Reproductive Physiology, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koji Kimura Laboratory of Reproductive Physiology, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ensuring the timely transport of gametes and embryos within the oviduct is essential for the successful establishment of pregnancy. This study investigated the direct effect of estradiol-17β (E2) on bovine oviductal contractility and the differences in responsiveness to E2 during the estrous cycle. Bovine isthmic tissues from four estrous stages were analyzed using the Magnus method to assess contractile responses to E2 and related reagents. Protein expression of G-protein-coupled estrogen receptor 1 (GPER1) and components of the RhoA/Rho kinase (ROCK) signaling pathway were also evaluated. E2 and a GPER1 agonist significantly increased oviductal tonus at 1–4 days after ovulation. This effect was significantly suppressed by treatment with a GPER1 antagonist and a ROCK inhibitor. At 1–4 days after ovulation, both ROCK II expression and ROCK activity were elevated. E2 also enhanced phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and myosin light chain (MLC), key downstream targets of ROCK. Before ovulation, when endogenous E2 levels peak, the expression of RND3―a ROCK inhibitor―was upregulated. The application of an RND inhibitor restored E2 responsiveness in oviductal tonus, ROCK activity, and the phosphorylation of MYPT1 and MLC in oviductal tissues before ovulation. These findings suggest that E2 directly increases oviductal tonus via GPER1 and ROCK/MYPT1/MLC activation at 1–4 days after ovulation. Differences in oviductal responsiveness to E2 during the estrous cycle appear to be mediated by the expression of ROCK and RND3. This mechanism can enable sperm transport within the oviduct at an appropriate time. No potential conflict of interest relevant to this article was reported.

Institute of Electrical and Electronics Engineers (IEEE) Acta Medica Okayama 2169-3536 14 2026 A Self-Adaptive Framework for Deploying Machine Learning Systems Without Ground-Truth Data at Runtime 30309 30326 EN Kento Furukawa Graduate School of Information Science and Technology, Osaka University Hiroyuki Nakagawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tatsuhiro Tsuchiya Graduate School of Information Science and Technology, Osaka University In recent years, the practical application of machine learning technology has rapidly progressed, accelerating its adoption across various fields. In this context, studies into the effective operation of machine learning systems in real-world environments have become essential. In actual operational settings, the distribution of input data often changes over time, leading to a significant decline in the predictive performance of models. Additionally, the lack of ground-truth data for test data during operation can sometimes make adaptation through retraining difficult. This study proposes a framework that autonomously adapts to changes in input data distribution, even in environments where ground-truth data for test data is unavailable during operation. This framework analyzes the distribution of input data and selects the appropriate predictive model based on the state of the distribution. To ensure optimal model selection, the framework employs two complementary approaches: 1) dynamically switching between multiple pre-trained models with different feature sets according to environmental changes and 2) building ensemble models based on the distribution of the test data. These approaches enable the framework to autonomously adapt to shifts in data distribution, even in operational settings where ground-truth data is unavailable. Evaluation experiments using both simulated and real-world data assessed the predictive performance of the proposed method through metrics such as R2, RMSE, and MAE. Compared to conventional single model predictions, the proposed method consistently demonstrated higher accuracy. These results indicate that the proposed approach effectively adapts to data distribution shifts in operational environments where ground-truth data is unavailable. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0143-4160 135 2026 Regulation of brain-specific kinases 1 and 2 (BRSK1/2) by Ca2+/calmodulin 103134 EN Naoyuki Washida Moe Kataoka Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Anna R. Brun Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Uryu Takezaki Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ko Hijikawa Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Haruki Yamauchi Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, 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 Ryo Morishita CellFree Sciences Co., Ltd. Hiroshi Tokumitsu Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University We conducted a genome-wide calmodulin (CaM) interaction screening of 462 GST-fused human protein kinases to identify novel CaM-dependent protein kinases (CaMKs). In addition to known CaMKs, including myosin light chain kinases, CaMK2γ, and death-associated kinase 2, we identified the brain-specific protein kinase 2 (BRSK2, also known as SAD-A) as a novel CaM interactant. Proximity biotinylation and CaM–sepharose chromatography assays revealed that rat BRSK isoforms (BRSK1/2) interact with CaM in a Ca2+-dependent manner in vitro. We found that CaM suppresses the activation-loop phosphorylation of BRSK1 (at Thr189) and BRSK2 (at Thr175) by liver kinase B1 (LKB1), an activating kinase, in a Ca2+-dependent manner (IC50 of ∼7 µM), thereby inhibiting BRSK activation. LKB1-catalyzed phosphorylation of the catalytic domain mutant of BRSK1 (residues 1–294) at Thr189 was suppressed by the addition of Ca2+/CaM, consistent with direct CaM binding of the kinase domain, as well as wild-type BRSK1. We confirmed that the LKB1 activity was not directly suppressed by Ca2+/CaM, supporting the hypothesis that the direct interaction of Ca2+/CaM with the kinase domain blocks the phosphorylation/activation of BRSK1/2 by LKB1. The kinase activity and PP2Cα-catalyzed dephosphorylation of LKB1-phosphorylated BRSK1 were not altered by Ca2+/CaM, although it was demonstrated to bind to Ca2+/CaM like that of unphosphorylated BRSK1. This unrecognized mechanism of BRSK1/2 regulation, involving the direct role of Ca2+/CaM binding, which inhibits phosphorylation/activation by LKB1, may open a new Ca2+ signal transduction pathway in neurons. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2662-4443 6 1 2025 From localized 4f electrons to anisotropic exchange interactions in ferromagnetic CeRh6Ge4 269 EN Shoichiro Itokazu Department of Physics, Okayama University Akimitsu Kirikoshi Research Institute for Interdisciplinary Science, Okayama University Harald O. Jeschke Research Institute for Interdisciplinary Science, Okayama University Junya Otsuki Research Institute for Interdisciplinary Science, Okayama University CeRh6Ge4 is a cerium-based ferromagnetic material exhibiting a quantum critical behavior under pressure. We derive effective exchange interactions, using the framework of density functional theory combined with dynamical mean-field theory. Our results reveal that the nearest-neighbor ferromagnetic interaction along the c axis is isotropic in spin space, leading to a formation of spin chains. On the other hand, the inter-chain coupling is highly anisotropic: The in-plane moment weakly interacts ferromagnetically in the a–b plane to stabilize the ferromagnetic state, whereas the z-component couples antiferromagnetically, contributing to its destabilization. The magnetic anisotropy of the interchain interactions as well as of the local 4f wavefunctions characterizes the magnetic properties underlying the ferromagnetic transition and the quantum critical behavior in CeRh6Ge4. No potential conflict of interest relevant to this article was reported.

岡山大学法学会 Acta Medica Okayama 0386-3050 75 3-4 2026 表紙・目次 EN No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構 教師教育開発センター Acta Medica Okayama 2186-1323 16 2026 知的障害高等特別支援学校における SWPBS 第１層支援 ―キャンペーン方式の導入とその効果― 205 219 EN Hideaki TOKIMITSU Graduate School of Education (Professional Degree Course), Okayama University Yoshio MIYAZAKI Faculty of Education, Okayama University Madoka KOYAMA Kurashiki Kotoura Special Needs Seni or High School, Okayama Prefecture 10.18926/CTED/70370 　本研究は，軽度知的障害のある後期中等教育段階の公立知的障害高等特別支援学校において，SWPBS 第1層支援としてキャンペーン方式の支援を実施し，その効果検証を行った。方法としては，Ｘ学年生徒24名に対して挨拶行動の促進を狙ったキャンペーンを実施し，目標行動の生起数についてABフォローアップデザインを用いて検討した。また，Ｘ学年教員6名に対し，社会的妥当性を評価するアンケートを実施した。その結果，キャンペーンの介入直後に目標行動の生起数および目標行動に従事した生徒の割合の増加が見られ，キャンペーン終了後もベースラインと比較した増加が一定期間確認された。また，一定程度の社会的妥当性も確認できた。 No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構 教師教育開発センター Acta Medica Okayama 2186-1323 16 2026 地域社会とグローバルをつなぐ和楽器音楽次世代育成の実践研究（３） 小中学生の質問紙調査に見る「異文化間能力」育成の可能性 91 105 EN Rinko HAYAKAWA Okayama University Yuko BEPPU Kurashiki City College Miho YAMAJI Part-time Lecturer at Okayama University Yoko HANAKUSA Research Student at the Joint Graduate School in Science of School Education Hyogo University of Teacher Education Noriko TAKESHITA Biwako-Gakuin University Hiromi TAKASU Okayama University Keiko MIYOSHI Research Student at the Joint Graduate School in Science of School Education Hyogo University of Teacher Education Naoko SHIMIZU Doctoral Student at the Joint Graduate School in Science of School Education Hyogo University of Teacher Education Chihiro TOSA Yamaha Corporation Ai NAKAMURA Doctoral Student at the Joint Graduate School in Science of School Education Hyogo University of Teacher Education Aki HIGUCHI Okayama Prefectural School for the Deaf 10.18926/CTED/70362 　本研究は，「おかやま国際和楽器学生フェスティバル」の実践における，異文化間能力育成の可能性について，参加した小中学生の質問紙調査結果から検討した。<br> 　その結果，１）体験を通して形成された新たな認識により，和楽器音楽文化と自己との関係性を再認識・再構築し，和楽器音楽文化への積極的な関与を示す価値づけ・意味づけが行われ，内在化が促されたこと，２）越境文化としての和楽器音楽文化に対して，開放的・尊重的態度を示していたが，自己の文化的アイデンティティを意識する契機となったこと，３）和楽器音楽の共有を通して生じた共感の上に，相互理解や協働関係が構築されていたこと，４）「文化の共有の可能性についての認識」が形成されるなど，フェスティバルでの経験が，文化観の形成に影響を与える契機となっていたこと，が明らかになった。 No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構 教師教育開発センター Acta Medica Okayama 2186-1323 16 2026 説明的文章の指導における「内省」を促す批判的読み ―高等学校１年生を対象として― 15 29 EN Yumi SAISHO Graduate School of Education (Professional Degree Corse), Okayama University Masafumi IKEDA Faculty of Education, Okayama University 10.18926/CTED/70357 　批判的読みは，現代では欠かせない能力であり，学習指導要領にも明記されている。近年，批判的読みの指導に関する研究がなされているものの，内容的な価値の検討や社会的な文脈のなかで捉えることが希薄だとする指摘や，「反省性」という観点に着目した批判的読みを求める声もある。そこで，本稿では，文章そのものを批判的に読むだけでなく，自身の持っている考えをも批判的に捉える（内省する）ことを促す授業を開発した。その手立てとして，複数の社会認識が存在する二つの教材の読み比べたうえで，対立する立場からの意見交換を行うことや，教材に対する評価の記述，その記述（自己の読み）を学習者自身が評価するといった活動を取り入れた。学習者の記述の分析からは，意識的な内省に至らなかった学習者も見受けられたものの，約６割の学習者の記述には変容が見られ，用いた手立ては効果があったと推測できることを指摘した。 No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構 教師教育開発センター Acta Medica Okayama 2186-1323 16 2026 外国人幼児の就学支援における保育士の工夫と実践的課題 1 13 EN Yiwen CHEN The Joint Graduate School (Ph.D. Program) in Science of School Education, Hyogo University of Teacher, Hyogo University of Teacher Education Kazuki YANAGISAWA Graduate School of Education, Okayama University Xinyu REN Graduate School of Education, Okayama University Munehisa YOSHITOSHI Faculty of Education, Okayama University 10.18926/CTED/70356 　本研究は，外国人幼児が就学期に直面する困難に対応するため，保育士が行っている具体的な保育実践における支援の工夫と課題を明らかにすることを目的とした。外国人幼児の支援経験を有する保育士2 名に半構造化インタビューを行い，SCAT を用いた質的分析により，幼児および保護者への支援内容を整理した。その結果，言語面では視覚的支援ややさしい日本語を活用し，文化面では家庭文化と日本の園文化の調整が行われていた。発達支援においては，非認知的スキルの育成や医療機関との連携の必要性が指摘された。保護者支援では，参加型の関わりや丁寧な説明が実践されていたが，制度情報の提供や行政との連携には課題が残された。これらの結果を踏まえ，今後は保育士の個別的努力に依存しないためにも，多文化背景をもつ家庭への支援を制度的に支える地域連携体制の整備や，情報提供の標準化，日本語教育資源との接続を図る実践的仕組みの構築が求められる。 No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構 教師教育開発センター Acta Medica Okayama 2186-1323 16 2026 岡山大学教育推進機構 教師教育開発センター紀要 第16号 全文（一括ダウンロード用） EN No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2192-4449 15 1 2026 A case of tubulointerstitial nephritis with infiltration of neutrophils and interleukin-17-positive cells associated with Behçet’s disease 35 EN Naruhiko Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Keiko Tanaka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Natsuki Kubota Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Tanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Behçet’s disease (BD) is a non-infectious inflammatory condition characterized by neutrophilic infiltration. In addition to primary symptoms, including oral and genital ulcers, ocular involvement, and skin lesions, BD can also affect various organs. However, renal involvement, particularly in tubulointerstitial nephritis, has rarely been described. Herein, a rare case of acute tubulointerstitial nephritis in a patient clinically diagnosed with BD is reported. The renal lesion presented with other symptoms of BD and fever, and was considered to be BD-related due to the presence of neutrophilic infiltration and its responsiveness to BD-directed therapy. Alterations in T-helper (Th) 1, Th2, and Th17 cytokine profiles are associated with BD activity. Interleukin (IL)-17 plays a central role in neutrophil activation, and recent studies have demonstrated a strong correlation between IL-17A levels and BD activity. In the present case, elevated serum IL-17A levels and infiltration of IL-17A-positive cells into the renal tissue reflected an active phase of BD and a BD-associated renal lesion. No potential conflict of interest relevant to this article was reported.

岡山大学農学部附属山陽圏フィールド科学センター Acta Medica Okayama 0910-8742 46 2024 教育 : 2023年度 1 6 EN No potential conflict of interest relevant to this article was reported.

岡山大学農学部附属山陽圏フィールド科学センター Acta Medica Okayama 0910-8742 46 2024 表紙 EN No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1467-5463 27 1 2026 SGCRNA: spectral clustering-guided co-expression network analysis without scale-free constraints for multi-omic data bbag021 EN Tatsunori Osone Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoka Takao Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shigeo Otake Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeshi Takarada Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Weighted gene co-expression network analysis (WGCNA) is among the most widely employed methods in bioinformatics. WGCNA enables the identification of gene clusters (modules) exhibiting correlated expression patterns, the association of these modules with traits, and the exploration of candidate biomarker genes by focusing on hub genes within the modules. WGCNA has been successfully applied in diverse biological contexts. However, conventional algorithms manifest three principal limitations: the assumption of scale-free topology, the requirement for parameter tuning, and the neglect of regression line slopes. These limitations are addressed by SGCRNA. SGCRNA provides Julia functions for the analysis of co-expression networks derived from various types of biological data, such as gene expression data. The Julia packages and their source code are freely available at https://github.com/C37H41N2O6/SGCRNAs.jl. No potential conflict of interest relevant to this article was reported.

BON VIEW PUBLISHING PTE Acta Medica Okayama 2810-9503 5 1 2025 A Study on Zeek IDS Effectiveness for Cybersecurity in Agricultural IoT Networks 133 142 EN Samsul Huda Interdisciplinary Education and Research Field, Okayama University Muhammad Bisri Musthafa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University S. M. Shamim Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yasuyuki Nogami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University As agriculture moves toward Agriculture 4.0, which uses Internet of Things (IoT) devices to collect data in real time and monitor things from a distance, these networks are becoming increasingly vulnerable to cyberattacks. A common method used to protect against these kinds of threats is the use of intrusion detection systems (IDS). However, the agricultural environment is often changing and has limited resources, which makes cybersecurity challenging. Several available IDS tools are not designed to work properly in places with few resources, intermittent access, and unpredictable network conditions. This paper investigates the performance of Zeek, an open-source IDS, in identifying potential threats in agricultural IoT networks. We performed both offline and real-time experiments: offline analysis used pcap files from the Stratosphere Laboratory dataset, and real-time evaluation involved simulated live attack scenarios, focusing on unauthorized access attempts and distributed denial-of-service (DDoS) attacks. Zeek's performance was assessed based on CPU and memory utilization, as well as quality of service (QoS) metrics. From the experimental results, we found that Zeek was quite effective in protecting agricultural IoT networks against typical threats. Memory usage remained stable around 5% during offline analysis and under 20% during active attacks. However, CPU usage was more volatile, peaking at 120% during DDoS events. In terms of QoS, the system maintained a good throughput (1,375 kbits/s) with minimal packet loss (0.000186%). Among the attack types that we tested, brute force attacks, which represent attempts at unauthorized access, had the strongest effect on network performance, increasing delay to 2.159 ms and jitter to 0.793 ms. It seems clear that a heavier traffic load during such attacks can interfere with QoS. On the basis of our observation, we recommend practical deployment strategies for agricultural IoT systems that take these limitations into consideration, aiming to keep networks both secure and efficient under pressure. No potential conflict of interest relevant to this article was reported.

岡山大学大学院ヘルスシステム統合科学研究科 Acta Medica Okayama 2436-3227 6 2026 The effects of cold compresses on itching in patients with atopic dermatitis: A cross-over controlled pilot trial 1 6 EN Yuki HIRAMI Former Department of Nursing, Graduate School of Health Sciences, Okayama University Nahoko HARADA Department of Nursing Science, Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Miho ONO Department of Nursing, Faculty of Health, Kagawa Prefectural University of Health Sciences Masahide KODA Co-learning Community Healthcare Re-innovation Office, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kiyoko FUKAI Professor Emeritus, Okayama University, Graduate School of Nursing, The Jikei University School of Medicine 10.18926/interdisciplinary/70325 This cross-over controlled trial aimed to evaluate the effectiveness and safety of two types of cold compresses (towels and ice packs) in alleviating itching among patients with atopic dermatitis. The study recruited 19 participants diagnosed with atopic dermatitis and suffering from chronic itching for over 6 months. Each participant received both types of cold compress interventions. Itching sensations were assessed repeatedly using a visual analogue scale before and after the application of the cold compress. The mean and standard deviation of itching scores for the towel intervention were 16.9 ± 19.1 (baseline) and 11.4 ± 16.1 (post-application). For the ice pack intervention, the scores were 13.6 ± 14.7 (baseline) and 6.2 ± 9.8 (post-application). Although there was a reduction in mean itching scores following the application of cold compresses, the differences were not statistically significant for either intervention. Despite the lack of statistical significance, this study suggests that cold compresses, which are user-friendly and inexpensive, may safely reduce subjective itching in patients with atopic dermatitis without causing pain or discomfort. However, further research with a larger sample size is needed to confirm these findings. No potential conflict of interest relevant to this article was reported.

岡山大学大学院ヘルスシステム統合科学研究科 Acta Medica Okayama 2436-3227 6 2026 表紙・目次 EN No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Tribolium castaneum with longer duration of tonic immobility have more variations corresponding to the human Parkinson’s disease genomic region 8840 EN Keisuke Tanaka NODAI Genome Research Center, Tokyo University of Agriculture Ken Sasaki Graduate School of Agriculture, Tamagawa University Shunsuke Yajima NODAI Genome Research Center, Tokyo University of Agriculture Takahisa Miyatake Faculty of Environmental, Life, Natural Science and Technology, Okayama University Parkinson’s disease (PD) is a common neurodegenerative syndrome characterized by the loss of dopaminergic neurons and is also a progressive neurodegenerative disorder that is characterized by dopamine deficiency. We established strains artificially selected for longer and shorter durations of tonic immobility, an antipredator behavior that has received much attention recently, in the red flour beetle, Tribolium castaneum, a model insect species for molecular analyses different from Drosophila melanogaster. Previous studies have shown that the long strains (L-strain) have significantly lower levels of dopamine expression in the brain than the short strains (S-strain) and that they have an abnormal pattern of locomotor activity. Furthermore, previous studies have shown that administering dopamine to L-strain beetles reduces the duration of tonic immobility. Transcriptome analysis of brain and thorax of the L- and S-strains also showed differences in mRNA expression of genes involved in dopamine synthesis and tyrosine metabolism. These results indicate that the phenotype and molecular basis of the L-strain are similar to those of Parkinson’s syndrome symptoms. In order to establish a link between T. castaneum and PD, we compared the DNA sequences of the L- and S-strains to human genes affecting dopaminergic pathways. The DNA comparison revealed many mutated regions in these genes in the L-strain. We discuss the relationship between dopaminergic pathway genes and PD-like phenotypes across humans, Drosophila, and the red flour beetle. No potential conflict of interest relevant to this article was reported.

Asian Agricultural and Biological Engineering Association Acta Medica Okayama 1881-8366 19 1 2026 Biosensing method of growth diagnosis in the forced culture of strawberries ―Development of crop-identification algorithms― 42 50 EN Shogo TSUBOTA Institute of Agricultural Machinery, National Agriculture and Food Research Organization Kazuhiko NAMBA Faculty of Environmental, Life, Natural Science and Technology, Okayama University Shota KASEI Institute of Agricultural Machinery, National Agriculture and Food Research Organization Tokihiro FUKATSU Institute of Agricultural Machinery, National Agriculture and Food Research Organization An image-processing algorithm for identifying individual crops is developed for labor-savings and time-series biological information collection. Information including the leaf development frequency are diagnostic indicators of strawberry growth. The algorithm is designed for drones in greenhouses that cannot acquire location information using the global navigation satellite system (GNSS). Drones fly over crop rows and sequentially assign identification numbers (IDs) to crops. Object-detection artificial intelligence (AI) is used to estimate the crop zone, and the ID is based on the crops number difference between frames. The previous misdetection rate was 1.06 %, failing to identify crops, which decreases to 0.31 % using the proposed algorithm. Furthermore, because there are no failures in consecutive frames, IDs are assigned to all crops correctly. No potential conflict of interest relevant to this article was reported.

岡山大学教育学部国語研究会 Acta Medica Okayama 2189-5414 40 2026 訓読漢詩の音読について ―音読台本のすすめ― (1) (12) EN No potential conflict of interest relevant to this article was reported.

岡山大学教育学部国語研究会 Acta Medica Okayama 2189-5414 40 2026 魯迅「故郷」論 ―〈高い壁〉の中の「私」― 1 17 EN No potential conflict of interest relevant to this article was reported.

岡山大学教育学部国語研究会 Acta Medica Okayama 2189-5414 40 2026 表紙 EN No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0923-1811 119 1 2025 Big data-driven target identification by machine learning: DRD2 as a therapeutic target for psoriasis 9 17 EN Takashi Sakai Department of Dermatology, Faculty of Medicine, Oita University Ryusuke Sawada Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Otoha Ichinose Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology Takeshi Terabayashi Department of Pharmacology, Faculty of Medicine, Oita University Yutaka Hatano Department of Dermatology, Faculty of Medicine, Oita University Yoshihiro Yamanishi Department of Complex Systems Science, Graduate School of Informatics, Nagoya University Toshimasa Ishizaki Department of Pharmacology, Faculty of Medicine, Oita University Background: The development of medical treatments has traditionally relied on researchers leveraging scientific knowledge to hypothesize disease mechanisms and identify therapeutic agents. However, the depletion of novel therapeutic targets has become a significant challenge, resulting in stagnation within pharmaceutical research.<br> Objective: To address the scarcity of therapeutic targets, we developed a machine learning (ML)-based system capable of predicting therapeutic target molecules for diseases. To validate its utility, we applied this system to psoriasis, aiming to identify novel treatment strategies.<br> Methods: Our approach utilized a large clinical database to calculate reporting odds ratios for all drugs associated with the prevention of diseases of interest. We identified target proteins by analyzing large chemical structure databases to discover proteins commonly associated with preventive drug candidates. Experimental validation was conducted by administering a predicted therapeutic candidate in an imiquimod-induced psoriasis mouse model.<br> Results: The ML-based predictions identified drugs for Parkinson’s disease as potential preventive candidates for psoriasis. Further analysis highlighted dopamine receptor D2 (DRD2) as a therapeutic target. Administration of a DRD2 agonist alleviated psoriasis symptoms in mice, evidenced by the downregulation of mRNA expression in the IL-17 pathway and reduced serum tumor necrosis factor-α levels.<br> Conclusion: This study demonstrates the utility of a novel ML-based system for identifying therapeutic targets, as shown by its successful application in uncovering the role of DRD2 in psoriasis. Beyond psoriasis, this system offers significant potential for exploring pathological mechanisms and discovering therapeutic targets across various diseases. No potential conflict of interest relevant to this article was reported.

Japan Society of Mechanical Engineers Acta Medica Okayama 1880-5558 20 1 2025 Numerical analysis validating the standard k-epsilon model for the kinetic energy of turbulence subjected to weak but long-lasting wind tunnel blockage acceleration JFST0004 EN Akira ONO Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroki SUZUKI Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Toshinori KOUCHI Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kento TANAKA Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The aim of this study is to investigate the effect of weak but prolonged mean flow accelerations, such as those observed in wind tunnel blockage acceleration, on free-stream turbulence. Specifically, this research aims to validate a model previously developed based on the k-epsilon model. To test this model, the study focuses on scenarios where the turbulence under acceleration is steady and isotropic, since the model suggests that this type of acceleration has no effect on the turbulent kinetic energy. To examine this suggestion, the turbulence within a periodic box was analyzed using large-eddy simulation (LES) based on the conventional Smagorinsky model framework. The numerical analysis is based on a method that conserves velocity fluctuation intensities. The results show that while high rate of acceleration deviates turbulent kinetic energy, low rate acceleration has hardly any effect on turbulent kinetic energy, enstrophy, pressure fluctuation, relative pressure fluctuation intensity, and higher-order statistics of a velocity fluctuation. These results validate the accuracy of the model proposed in the previous studies. These results were obtained by focusing on differences in Reynolds numbers and the spatial scale of the forcing. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2075-4418 16 6 2026 Seasonal Variations in the Risk of Outpatient Acute Kidney Injury in Patients with Chronic Kidney Disease 845 EN Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naruhiko Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Haraguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinji Kitamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Acute kidney injury (AKI) frequently occurs in the outpatient setting and is associated with adverse renal and survival outcomes. However, there is no established definition of outpatient AKI, and the risk factors, especially seasonal variation, remain limited. This study aimed to investigate seasonal variation in the risk of outpatient AKI. Methods: This retrospective observational study used routinely collected clinical laboratory data from a single hospital in Japan between 2007 and 2022. Outpatient AKI was defined as ≥35% relative decline in estimated glomerular filtration rate (eGFR) compared with a preceding outpatient measurement obtained within 14–90 days. Monthly and seasonal variations in outpatient AKI risk in patients with chronic kidney disease (CKD) were evaluated using logistic regression models. Subgroup analyses were performed according to AKI stage, age group, and CKD stage. Results: A total of 203,853 outpatient records were analyzed. The incidence of outpatient AKI was highest in August and lowest in November. Analyses demonstrated significantly increased odds ratios of outpatient AKI in January, February, July, and August. Seasonally, the risk was significantly higher during the summer. Stage-specific analyses showed that AKI stage 1 was more frequent in the summer, whereas AKI stage 2 tended to increase during the winter. Conclusions: Outpatient AKI exhibits distinct seasonal patterns, with increased risk during both summer and winter and differential associations according to AKI severity and baseline kidney function. Recognition of these patterns may help identify vulnerable populations and inform targeted preventive strategies for outpatient AKI. No potential conflict of interest relevant to this article was reported.

The Company of Biologists Acta Medica Okayama 1754-8403 19 2 2026 A genetic model of congenital intestinal atresia implicates Mypt1 in epithelial organisation dmm052605 EN Daisuke Kobayashi Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine Akihiro Urasaki Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine Tetsuaki Kimura Medical Genome Center, Research Institute, National Center for Geriatrics and Gerontology Satoshi Ansai Ushimado Marine Institute, Okayama University Kazuhiko Matsuo Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine Hayato Yokoi Graduate School of Agricultural Science, Tohoku University Shigeo Takashima Institute for Glyco-core Research (iGCORE)/Life Science Research Centre, Gifu University Tadao Kitagawa Program in Environmental Management, Graduate School of Agriculture, Kindai University Takahiro Kage Department of Biological Sciences, Graduate School of Science, The University of Tokyo Takanori Narita Laboratory of Molecular Biology, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University Tomoko Jindo Department of Biological Sciences, Graduate School of Science, The University of Tokyo Masato Kinoshita Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University Kiyoshi Naruse Laboratory of Bioresources, National Institute for Basic Biology Yoshiro Nakajima Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine Masaki Shigeta Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine Shinichiro Sakaki Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine Satoshi Inoue Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine Rie Saba Department of Radiology, Kyoto Prefectural University of Medicine Kei Yamada Department of Radiology, Kyoto Prefectural University of Medicine Takahiko Yokoyama Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine Yuji Ishikawa Research Centre for Radiation Protection, National Institute of Radiological Sciences Kazuo Araki Research Center for Aquatic Breeding, National Research Institute of Aquaculture, Fisheries Research Agency Yumiko Saga Department of Biological Sciences, Graduate School of Science, The University of Tokyo Hiroyuki Takeda Department of Biological Sciences, Graduate School of Science, The University of Tokyo Kenta Yashiro Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine Congenital intestinal atresia (IA) is a birth defect characterised by the absence or closure of part of the intestine. Although genetic factors are implicated, mechanistic understanding has been hindered by the lack of suitable animal models. Here, we describe a medaka (Oryzias latipes) mutant, generated by N-ethyl-N-nitrosourea (ENU) mutagenesis, that develops IA during embryogenesis. Positional cloning identified a nonsense mutation in mypt1, encoding myosin phosphatase target subunit 1. Mutant embryos exhibited ectopic accumulation of F-actin and phosphorylated myosin regulatory light chain (Mrlc) in the intestinal epithelium, consistent with disrupted actomyosin regulation. These cytoskeletal abnormalities were accompanied by epithelial disorganisation, without notable alterations in cell proliferation, motility or apoptosis. Inhibition of myh11a, encoding smooth muscle (SM) myosin heavy chain, ameliorated the IA phenotype, whereas blebbistatin treatment completely rescued the defect, suggesting a non-contractile role prior to SM maturation. Together, these findings demonstrate that mypt1 loss disrupts intestinal morphogenesis through actomyosin dysregulation. Given the recent clinical identification of IA associated with MYPT1 variants, this medaka model offers a valuable platform to investigate the developmental and molecular basis of MYPT1-associated IA in humans. No potential conflict of interest relevant to this article was reported.

岡山大学理学部地球科学科 Acta Medica Okayama 1340-7414 32 1 2026 裏表紙・目次 EN No potential conflict of interest relevant to this article was reported.

岡山大学理学部地球科学科 Acta Medica Okayama 1340-7414 32 1 2026 岡山大学地球科学研究報告 投稿規定（約款） EN No potential conflict of interest relevant to this article was reported.

岡山大学理学部地球科学科 Acta Medica Okayama 1340-7414 32 1 2026 2018年7月5日〜7日の西日本豪雨における広域降水特性 33 44 EN Kuranoshin KATO Faculty of Education, Okayama University Kengo MATSUMOTO Okayama Gakugeikan High School Kazuo OTANI TV Setouchi Broadcasting Co., LTD. 10.18926/ESR/70297 　Large-scale rainfall characteristics at the heavy rainfall event around the western Japan for 5–7 July 2018 were analyzed with use of the 10-mimute precipitation data at the surface meteorological observation stations of the Japan Meteorological Agency, and so on. In this case, the area with 3 days total precipitation of near or more than 300 mm was distributed widely from northern Kyushu to Shiga and Fukui Prefectures. As in the many heavy rainfall events around Kyushu District in the mature stage of the Baiu season, contribution of the intense rainfall with more than 4 mm/10-minute (24 mm/h) attained about one third of the areal mean total precipitation. However, it is noted that the "not so intense rain" with less than 2 mm/10-minute (12 mm/h) also contributed to about one third of the huge total precipitation in the wide area. In short, this case could be characterized by the mixture of the western Japan type heavy rainfall event and the eastern Japan type one. No potential conflict of interest relevant to this article was reported.

岡山大学理学部地球科学科 Acta Medica Okayama 1340-7414 32 1 2026 10分間降水量から大雨の特徴の多様性を捉える大学での授業の試み（防災気象リテラシー育成へ向けて） 21 31 EN Kuranoshin KATO Faculty of Education, Okayama University 10.18926/ESR/70296 　In the disaster prevention education on the heavy rainfall around Japan, it is also important to promote the meteorological literacy on the seasonal and regional differences of their rainfall characteristics such as the convective rain or stratiform rain, together with their total amount of precipitation and their occurrence frequency. As the first step toward the above purpose, the present study made a lesson practice for the university students by utilizing the 10-minute precipitation data for the four heavy rainfall events, in which the types of the heavy rainfall (although all the cases examined in the lesson are relating to the deep convective clouds) are rather different from each other, such as the differences of the rainfall intensity at the peak time, short-period variation of the rainfall intensity and the persistency of the rainfall including the "not so intense rainfall". The reports by the students seem to perceive the different features among these events briefly, but the students' attention to how long the intense rainfall with short-period variation or "not so intense rainfall" lasted was not so sufficient. No potential conflict of interest relevant to this article was reported.

岡山大学理学部地球科学科 Acta Medica Okayama 1340-7414 32 1 2026 寒風古窯跡群須恵器の岩石学的研究 9 19 EN Taiji ANAMI Department of Earth Sciences, Okayama University Toshio NOZAKA Department of Earth Sciences, Okayama University Osamu KIMURA Department of Archaeology, Osaka University 10.18926/ESR/70295 　The Sabukaze kiln site, a representative ancient tunnel-kiln site in the Kibi region, worked during the Asuka period (from early 7th century to early 8th century) to produce Sue ware including jars, cups, coffins, and ornamental tiles. To determine the provenance of the materials used for the Sue ware, we carried out petrological analyses of 13 Sue sherds, including optical microscopy, X-ray diffractometry, X-ray fluorescence spectroscopy, Raman spectroscopy, and electron-probe analysis. In spite of the difference of production time, all the Sue sherds show close similarities in modal proportion of mineral inclusions with dominant quartz and feldspar, and minor volcanic glass, in chemical compositions of feldspar and interstitial matrix, and in whole-sherd chemical composition. These similarities suggest that the paste materials of the Sabukaze Sue ware were commonly derived from weathered rhyolitic rocks and obtained from the same or neighboring mining site(s) located near the kiln site. No potential conflict of interest relevant to this article was reported.

岡山大学理学部地球科学科 Acta Medica Okayama 1340-7414 32 1 2026 岡山平野児島湾岸部での微動アレイ探査 1 7 EN Nobuyuki YAMADA Faculty of Science and Technology, Kochi University Hiroshi TAKENAKA Department of Earth Sciences, Okayama University 10.18926/ESR/70294 　This report describes microtremor array observations conducted at two sites for deep exploration and three sites for shallow exploration around Kojima Bay area in the southern Okayama Plain. Based on these records, the ground velocity structures were estimated. The results yielded solutions indicating the depth of the top of the seismic base layer (equivalent to 3 km/s layer) ranges from 140 to 300 m, while the depth of the top of the engineering basement layer (equivalent to 0.6 km/s layer) is approximately about 13–14 m. The shallow exploration results also suggested the possible presence of an inversion layer. These estimated velocity structure models provided a reasonable explanation for the observed phase velocities. No potential conflict of interest relevant to this article was reported.

岡山大学理学部地球科学科 Acta Medica Okayama 1340-7414 32 1 2026 Title Page EN No potential conflict of interest relevant to this article was reported.

岡山大学理学部地球科学科 Acta Medica Okayama 1340-7414 32 1 2026 表紙・英文目次 EN No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 61 2026 『論語集注』訳注（子罕第九　（二）） (1) (20) EN Luyi SUN 10.18926/70285 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 61 2026 多文化共修のためのグループワークから学生は何を感じたのか？ ― GIS ソフトを使用した地域研究授業からの一考察 ― 1 20 EN Takao INAMORI 10.18926/70274 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 61 2026 表紙 EN No potential conflict of interest relevant to this article was reported.

岡山大学考古学研究室 Acta Medica Okayama 2026 岡山市向場・黒住丘陵の遺跡測量調査概要報告 EN 10.18926/70272 No potential conflict of interest relevant to this article was reported.

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

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.<br> 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.<br> 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.<br> 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.

岡山大学経済学会 Acta Medica Okayama 2433-4146 57 3 2026 AI 共生時代における消費者行動の再理論化―AIBCBM フレームワーク― 41 91 EN Sawut Shazadigul Faculty of Humanities and Social Sciences, Okayama University 10.18926/OER/70263 　本研究は，AIが意思決定の前段階から介入する環境において，企業・消費者・AIの三者相互作用を体系的に説明する理論枠組みとして，Artificial Intelligence-Based Consumer Behavior Model（AIBCBM）を構築し，提示することを目的とする。まず，既存の消費者行動モデルが，アルゴリズム露出，再帰的学習ループ，AI媒介型社会的影響（Algorithmic Social Influence）といった現代的現象を十分に扱えないという決定的な理論的限界を明らかにする。そのうえで，AI共生時代における消費者行動を，「企業−AI−消費者」の三者循環構造として捉えるAIBCBMを提示する。<br> 　モデル構築に際しては，複雑な現実を過度に単純化するのではなく，三者共進化構造モデル（図２），行動生成の動態を示す行動プロセスモデル（表３），概念構造モデル（図３），行動類型モデル（図４）に分離することで，理論的明瞭性と分析可能性を確保した。本研究の理論的貢献は，�@System １を行動生成メカニズムとして再定義した点，�A意思決定主体と権力構造を再定義した点，�B消費者行動における非線形・高速フィードバックループを理論化した点，�C非消費やJOMOを，幸福と主体性に根ざした戦略的行動として理論的に再定義した点，�D消費者行動を「意思決定モデル」から「行動生成モデル」へ理論的に転換した点に集約される。さらに，本研究が提示する，アルゴリズムによる効用の向上と自律性の毀損が併存しうるという二面性は，AI時代におけるマーケティング戦略および政策設計に対して，規範的かつ理論的な新たな評価軸を提供する。AIBCBMは，これらの視座を統合する理論的プラットフォームとして，今後の実証研究に向けた基盤として機能する。とりわけ， AIBCBMは，JOMOや非消費行動を，アルゴリズム環境からの受動的撤退ではなく，AIによって構築された選択環境との距離を意図的に調整し，人間らしさ（人間としての主体性やウェルビーイング）を保持するための戦略的行動として位置づける点に独自性を有する。さらに本モデルは，AI設計（企業側）・アルゴリズム動態（AI側）・主体性とウェルビーイング（Well-being）（消費者側）を同一枠組みで接続することで，AI共生時代の実証研究と規範設計を架橋する理論的座標軸を確立する。 No potential conflict of interest relevant to this article was reported.

岡山大学経済学会 Acta Medica Okayama 2433-4146 57 3 2026 地域間での情報交流に関するネットワーク分析：高梁川流域圏での調査による 11 40 EN Ryohei Nakamura Natsumi Yokota 10.18926/OER/70262 　本稿では，岡山県の「高梁川流域連携中枢都市圏」で2014年から開催されている「高梁川流域経済成長戦略会議」における参加主体間の情報交流についてのネットワーク分析を行った。高梁川流域連携中枢都市圏（高梁川流域圏）とは，岡山県高梁川周辺に位置する現在の新見市，高梁市，総社市，早島町，倉敷市，矢掛町，井原市，浅口市，里庄町，笠岡市の10自治体が参加している連携中枢都市圏である。高梁川流域圏におけるネットワーク分析に際しては，同圏域内で展開されている事業を８つに分類し，それぞれの事業に関する参加主体間の情報交流についてアンケート調査を行った。ネットワーク指標については事業ごとに次数中心性と媒介中心性の中心性指標を，また事業別に密度，推移性，相互性を算出した。事業別にみると，観光事業についての情報交流が最も密なネットワーク構造をしており，ネットワークの視点では観光事業が高梁川流域圏内で最も勢力的に行われている事業といえる。また全事業において特定の行政主体や商工会議所をはじめとする地域経済団体等の中心性指標が全体的に大きな値をとっており，ネットワークにおいて情報交流のハブや情報の集中・分散主体として機能していることが明らかになった。分析結果を踏まえ，ネットワークの視点から高梁川流域圏の今度の地域振興について２点提言した。１つは事業によって情報交流のハブや情報の集中・分散主体を主体間で分担することによって，すべての事業で密なネットワークを築くことを目指すことである。もう１つは高梁川流域圏の情報交流ネットワークに全く参加していない主体をなくすことで，全体的に密なネットワークを目指すことである。 No potential conflict of interest relevant to this article was reported.

岡山大学経済学会 Acta Medica Okayama 2433-4146 57 3 2026 1998年の外国為替及び外国貿易管理法改正と 外国通貨の譲渡による損益の所得区分 ―1998年の法改正は所得区分にどのような影響を与えたのか― 1 10 EN Yoshiyuki Nakagawa 10.18926/OER/70261 　1998年の外国為替及び外国貿易管理法の改正（以降，外国為替及び外国貿易法に改名）により，それまで外国為替公認銀行に原則として限られていた外国為替取引が，あらゆる企業及び個人に解放され，自由に行うことができるようになった。<br> 　本稿は，まず課税当局の「外国通貨の譲渡による損益は雑所得に該当する」との見解の判断根拠を，国会における政府参考人答弁及び東京地裁令和５年３月９日判決から読み解き，そのうえで，1998年の法改正により外国通貨取引が対外及び国内において何人も自由に行うことができるようになったことから，外国通貨は支払手段として言わば価値の尺度として機能するようになり，資産の値上がり，値下がりを観念することができなくなった結果として，その譲渡による所得区分が譲渡所得から雑所得へと変化したとの結論を導くものである。 No potential conflict of interest relevant to this article was reported.

岡山大学経済学会 Acta Medica Okayama 2433-4146 57 3 2026 表紙・目次 EN No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2666-6065 67 2026 Alcohol consumption, smoking, and the implications of their cessations for field carcinogenesis in the esophagus: a 10-year prospective cohort study 101798 EN Chikatoshi Katada Department of Medical Oncology, Kyoto University Graduate School of Medicine Tetsuji Yokoyama Department of Health Promotion, National Institute of Public Health Tomonori Yano Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East Yasuaki Furue Department of Endoscopy, Saitama Cancer Center Haruhisa Suzuki Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine Kenji Ishido Department of Gastroenterology, Kitasato University School of Medicine Keiko Yamamoto Division of Endoscopy, Hokkaido University Hospital Hiroyoshi Nakanishi Department of Gastroenterology, Ishikawa Prefectural Central Hospital Tomoyuki Koike Division of Gastroenterology, Tohoku University Graduate School of Medicine Masashi Tamaoki Department of Medical Oncology, Kyoto University Graduate School of Medicine Noboru Kawata Division of Endoscopy, Shizuoka Cancer Center Motohiro Hirao Department of Surgery, NHO Osaka National Hospital Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Ogata Department of Gastrointestinal Surgery, Kanagawa Cancer Center Atsushi Katagiri Division of Gastroenterology, Department of Medicine, Showa Medical University Hospital Takenori Yamanouchi Department of Gastroenterology, Kumamoto Regional Medical Center Hirofumi Kiyokawa Department of Gastroenterology, St. Marianna University School of Medicine Hirofumi Kawakubo Maki Konno Department of Gastroenterology, Tochigi Cancer Center Akira Yokoyama Department of Medical Oncology, Kyoto University Graduate School of Medicine Shinya Ohashi Department of Medical Oncology, Kyoto University Graduate School of Medicine Tai Omori Department of Surgery, Kawasaki Municipal Kawasaki Hospital Tadakazu Shimoda Department of Diagnostic Pathology, Shizuoka Cancer Center Atsushi Ochiai Exploratory Oncology Research and Clinicai Trial Center, National Cancer Center 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 Medical Oncology, Kyoto University Graduate School of Medicine Background Alcohol and tobacco are established carcinogens, which promote field carcinogenesis for esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the long-term effects of alcohol and tobacco cessations, and background mucosal status, on risk for metachronous ESCC (mESCC) after endoscopic resection (ER).<br> Methods This was a multicentre prospective cohort study of patients with intramucosal ESCC treated by ER. All participants received structured education on cessation, and underwent regular endoscopic surveillance. Patients were stratified by Lugol-voiding lesion (LVL) grade (A: none, B: 1–9, C: ≥10). The impacts of alcohol and smoking cessation on field carcinogenesis were assessed.<br> Findings Among 331 enrolled patients, the median follow-up was 120 months (range: 1.3–176.9). The cumulative incidences of mESCC were 10.4%, 27.2%, and 61.8% in grades A, B, and C, respectively. An increment of 1 unit (22 g ethanol) of alcohol consumption and higher LVL grade independently increased the risk for mESCC. Alcohol or smoking cessation reduced this risk (hazard ratio [HR] 0.52, 95% confidence interval [CI]: 0.31–0.88; HR 0.44, 95% CI: 0.25–0.78, respectively), and combined cessation had the greatest impact (HR 0.21, 95% CI: 0.07–0.65). Complete cessation, rather than partial reduction, was necessary to achieve meaningful risk reduction.<br> Interpretation Alcohol and tobacco exposure, and a large number of LVL, are major determinants of mESCC. Complete cessation markedly reduces risk, underscoring the importance of behavioural interventions for secondary prevention of field carcinogenesis after ER. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1478-811X 24 1 2026 MMP-3 cleavage of Lamin A induces pro-migratory nuclear deformity, nucleophagy, and their autophagic secretion with extracellular vesicles in metastatic cancer 146 EN Takanori Eguchi Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eman A. Taha Department of Biochemistry, Faculty of Science, Ain Shams University Keisuke Nakano Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Vikas Tiwari Council of Scientific & Industrial Research-Indian Institute of Toxicological Research Katsuki Takebe Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Inoue Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Lizi Xing Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chiharu Sogawa Department of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of Technology Kuniaki Okamoto Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Stuart K. Calderwood Division of Molecular and Cellular Biology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that cleave a plethora of substrates, including components of the extracellular matrix and cell-surface-associated proteins, as well as intracellular targets. MMPs have also been found in extracellular vesicles (EVs), such as exosomes. MMP-3 promotes tumor growth, epithelial-to-mesenchymal transition, genome instability, migration, invasion, and metastasis of cancer cells, and nuclear MMP-3 controls gene transcription. Intranuclear proteolysis by MMPs may significantly alter cancer progression. However, the nuclear substrates of MMP-3 have not been well investigated. In this study, we performed proteomic analyses to identify the nuclear substrates and EV proteins regulated by MMP-3. While rabidly metastatic colon cancer (LuM1) three-dimensionally cultured tumoroids secreted EVs containing 30 protein types, including Lamin A (LMNA), MMP-3, fibronectin (FN1), HSPA8 (Hsc70), β-actin (ACTB), and vimentin (VIM), CRISPR/Cas9-based knockout of MMP-3 reduced the secretion of these proteins in EVs. Notably, EV-bound cleaved Lamin secretion was confirmed by immunoelectron microscopy. Also, MMP-3 formed proteolytic dimers via its hemopexin-like repeat domains in nuclei. Many nuclear MMP-3-binding proteins, including Lamin A/C, histones, topoisomerases, and hnRNPs, were screened by co-immunoprecipitation followed by proteomics. Proteolytic MMP-3 overexpression generated a C-terminal 30-kDa fragment of Lamin A, whose cleavage site was defined via structural analysis. MMP-3 digestion of Lamin A induced nuclear deformity (atypia) required for cell migration in confined space. The cleaved Lamin A and MMP-3 were transported with autophagosomes (LC3B+), nucleophagosomes, and amphisomes (CD63 + LC3B+) and co-secreted with EVs. Proteolytic MMP-3 also induced nuclear speckles of Lamin A, suggesting their roles in transcription and splicing. Clinical analysis revealed that high expressions of MMP3 and LMNA were significantly seen in head and neck squamous cell carcinoma (HNSC) than in the other 16 cancer types, and predicted poor prognosis of patients suffering from HNSC, pancreatic, rectum and lung adenocarcinomas at specific stages. Immunohistochemistry revealed that nuclear MMP-3 and cleaved Lamin were significantly higher expressed in stage IV metastatic HNSC cases than in stage I non-metastatic cases. Taken together, MMP3-cleavage of Lamin A induces nuclear deformity, nucleophagy, and their autophagic co-secretion with EVs in metastatic cancer. Also, high expression of MMP-3 and secretion of Lamin A can predict poor prognosis in multiple cancer types at specific stages. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2055-0294 12 1 2026 Association between the incidence of infusion-related reactions by obinutuzumab and the dose of corticosteroid as premedication: a multicenter retrospective cohort study 27 EN Tatsuya Ohtsubo Department of Pharmacy, Japanese Red Cross Kyoto Daini Hospital Kazuhiro Yamamoto Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Saori Matumoto Department of Pharmacy, Japanese Red Cross Osaka Hospital Kaori Ito Faculty of Pharmacy, Meijo University Yuzuka Sasa Department of Pharmacy, Kindai University Hospital Kosuke Tomishima Department of Pharmacy, Japanese Red Cross Kyoto Daiichi Hospital Satoshi Dote Department of Pharmacy, Kyoto-Katsura Hospital Katuya Makihara Department of Pharmacy, Yodogawa Christian Hospital Yoshinori Wakasugi Department of Pharmacy, Shiga University of Medical Science Hospital Tsutomu Mitsuie Department of Pharmacy, Japanese Red Cross Otsu Hospital Kouhei Yamagiwa Department of Pharmacy, Saiseikai Shiga Hospital Kazuo Sato Department of Pharmacy, Japan Baptist Hospital Hiroki Hasegawa Department of Pharmacy, Rakuwakai Otowa Hospital Nobuhiko Uoshima Department of Hematology, Japanese Red Cross Kyoto Daini Hospital Yumi Kitahiro Department of Pharmacy, Kobe University Hospital Kanji Tomogane Department of Pharmacy, Japanese Red Cross Kyoto Daini Hospital Background Premedication with corticosteroids is recommended for prophylaxis against infusion-related reactions (IRRs) caused by obinutuzumab despite a lack of solid evidence regarding the dose of corticosteroids.<br> Methods The incidence rates of IRR in the high-dose and low-dose corticosteroid groups were investigated and compared using Student’s t-test.Univariable and multivariable logistic regression analyses were performed on patients to explore the risk of developing IRRs with obinutuzumab.<br> Results The incidence of IRRs in the high-dose and low-dose corticosteroid groups at the initial administration of obinutuzumab was 27.0% (41/152) and 48.4% (31/64), respectively, indicating that the high-dose group had a lower incidence of IRRs (p = 0.002). The incidence of IRRs at the initial administration of obinutuzumab was significantly associated with the administration of first-generation histamine 1 receptor antagonist (OR = 3.31, 95% CI: 1.16–9.47; reference: second-generation histamine 1 receptor antagonist), hydrocortisone (OR = 7.21, 95% CI: 1.57–33.15; reference: dexamethasone), and methylprednisolone (OR = 3.99, 95% CI :1.13–14.10; reference: dexamethasone), although no association was found with the lower dose of corticosteroids.<br> Conclusions Although no association was found between corticosteroid dosage and IRR when considering multiple factors, dexamethasone may be a better option than hydrocortisone or methylprednisolone for preventing IRR. Additionally, second-generation H1-receptor antagonists may be a better option than first-generation drugs. Certain combinations of premedications may influence infusion reaction incidence. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1478-6362 28 1 2026 Real-world comparative effectiveness of sarilumab versus Janus kinase inhibitors as monotherapy in rheumatoid arthritis 32 EN Yuji Nozaki Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Kazuya Kishimoto Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Tetsu Itami Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Daisuke Tomita Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Yumiko Wada Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University Takuya Kotani Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University Tohru Takeuchi Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University Toshihiko Hidaka Rheumatology Center, Miyazaki Zenjinkai Hospital Shoichi Hino Department of Rheumatology and Clinical Immunology, Izumi City General Medical Center Toshiaki Miyamoto Miyamoto Internal Medicine and Rheumatology Clinic Hirofumi Miyake Department of General Internal Medicine, Tenri Hospital Kazunari Hatta Department of General Internal Medicine, Tenri Hospital Kenji Mamoto Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka Metropolitan University Yutaro Yamada Center for Senile Degenerative Disorders (CSDD), Osaka Metropolitan University Graduate School of Medicine Tadashi Okano Center for Senile Degenerative Disorders (CSDD), Osaka Metropolitan University Graduate School of Medicine Takaichi Okano Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine Jun Saegusa Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine Masahiro Horita Department of Orthopaedic Surgery, Faculty of Medical Development Field, Okayama University Keiichiro Nishida Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Koji Kinoshita Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Shinya Rai Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Background: Sarilumab (SAR), an interleukin-6 receptor inhibitor (IL-6Ri), and Janus kinase inhibitors (JAKi) are approved options for rheumatoid arthritis (RA) when methotrexate (MTX) cannot be used. Real-world evidence for MTX-free monotherapy remains limited.<br> Methods: We conducted a multicenter retrospective cohort study of RA patients receiving SAR or JAKi as MTX-free monotherapy. To reduce confounding, 1:1 propensity score matching was performed in the overall cohort (n = 252, 126 per group) and separately within treatment-line strata: Phase 2 first-line biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs: 45 per group), Phase 3 second-line b/tsDMARDs (53 per group), and Phase 3 ≥ third-line b/tsDMARDs (47 per group). Outcomes over 12 months included drug retention, change in Clinical Disease Activity Index (CDAI), glucocorticoid (GC) tapering and discontinuation, low disease activity (LDA, CDAI ≤ 10), and safety profiles. Predictors of LDA were evaluated with logistic regression. This multicenter real-world.<br> Results: Across matched strata by prior b/tsDMARDs, retention and CDAI change did not differ significantly between SAR and JAKi through 12 months. When classified by cause, adverse events (AEs)-related discontinuation was higher with JAKi, yielding lower AE-specific retention. Both groups demonstrated GC sparing overtime, with a greater increase in GC discontinuation for SAR than for JAKi in Phase 2. Baseline predictors of achieving LDA at 12 months included higher C-reactive protein (CRP) and platelet count (Plt) in both groups, with additional associations of younger age and lower hemoglobin (Hb) in the SAR. In safety analyses, overall AEs were less frequent with SAR than with JAKi, driven by lower risks of infection including herpes zoster, while other categories were similarly infrequent.<br> Conclusion: SAR and JAKi showed no statistically significant differences in 12-month retention or disease control in MTX-free monotherapy settings. Higher CRP and Plt with lower Hb, particularly in younger patients, identified better response to SAR and support biomarker guided selection between IL-6Ri and JAKi. In Phase 2, GC discontinuation with SAR suggests a practical strategy to reduce AEs while maintaining efficacy. Prospective studies should validate these findings and define actionable thresholds. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2056-5933 12 1 2026 Dental infection is associated with early relapse in patients with ANCA-associated vasculitis e006392 EN Shoichi Nawachi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshia Miyawaki Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Moe Sakamoto-Tokunaga Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Natsuki Kubota Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuya Terajima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Hirose Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takato Nakadoi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manami Hirata-Watanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yu Katayama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keigo Hayashi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruki Watanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eri Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mariko Takano-Narazaki Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shigetomo Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-Ei Sada 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 Objectives Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic autoimmune disease where infections can trigger relapses. Dental infections, being common and associated with systemic inflammation, may play a role in AAV relapse, though their impact remains unclear. We aimed to evaluate the association between severe dental infections and early relapse in patients with AAV.<br> Methods This retrospective cohort study included patients newly diagnosed with AAV between January 2011 and July 2022. Patients with severe dental infections requiring tooth extraction were placed in the dental infection group, while the remaining patients were assigned to the control group. The primary outcome was defined as either vasculitis relapse or all-cause mortality within 1 year of treatment initiation. Adjusted HRs (aHRs) and 95% CIs were estimated using Cox proportional hazards models.<br> Results A total of 93 patients were enrolled with a median age of 74 years. 41 patients (44.1%) had severe dental infections in this cohort. Over the 1-year follow-up period, 13 patients experienced a relapse and two died, resulting in a composite event rate of 20.9 per 100 person-years. Dental infection was independently associated with the composite outcome (aHR, 3.78 (95% CI 1.13 to 12.66); p=0.031). Exploratory analysis indicated that composite outcome rates were similar regardless of tooth extraction among patients with dental infections.<br> Conclusions Severe dental infections were associated with increased risk of early relapse or mortality in AAV. These findings highlight the importance of early dental evaluation in AAV management. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0732-8893 115 3 2026 Investigation of the cefazolin inoculum effect in blood culture-isolated methicillin-susceptible Staphylococcus aureus strains: A Japanese multicenter study 117345 EN Shinnosuke Fukushima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuma Tsuji Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Sakura Ogawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihito Koyanagi Department of Clinical Laboratory, Chutoen General Medical Center Yuji Ito Department of General Internal Medicine, Chutoen General Medical Center Hiroshi Koganemaru Department of Infectious Diseases, Tokyo Metropolitan Institute for Geriatrics and Gerontology Atsushi Yoshida Department of Infectious Diseases, Tokyo Metropolitan Institute for Geriatrics and Gerontology Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background: Cefazolin inoculum effect (CInE) is a microbiological phenomenon where the MIC of cefazolin against methicillin-susceptible Staphylococcus aureus (MSSA) strains increases with higher bacterial volumes.<br> Method: We retrospectively investigated the prevalence and characteristics of the CInE among MSSA strains isolated from blood cultures at three Japanese hospitals. The collected isolates were screened for blaZ using PCR, and the cefazolin minimum inhibitory concentration (MIC) for the blaZ-positive MSSA isolates was measured at standard and high inoculum volumes. CInE-positive MSSA strains were defined as those with a cefazolin MIC ≥16 μg/mL at 107 CFU/mL and ≤8 μg/mL at 105 CFU/mL. In these blaZ-positive strains, we performed blaZ typing and tested a modified nitrocefin-based rapid examination to detect the CInE.<br> Results: We collected 329 MSSA strains isolated from blood cultures. Of these, 96 (29.2%) were positive for the blaZ gene, with the following genotypes: type A (15, 15.6%), type B (3, 3.1%), type C (77, 80.2%), type D (0, 0.0%), and non-type (1, 1.0%). Among 96 blaZ-positive MSSA isolates, 11 exhibited the CInE, all of which harbored blaZ type A. The rapid nitrocefin test detected CInE positivity with high sensitivity (100%), specificity (94.1%), and diagnostic accuracy (94.8%).<br> Conclusion: This study highlighted the low prevalence of CInE-presenting MSSA isolates in Japan. When the cefazolin MIC is ≥1 μg/mL or the penicillin G MIC is ≥0.25 μg/mL, the rapid nitrocefin test may be useful for considering the CInE in patients with high bacterial volume MSSA infections. No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 2041-4889 16 1 2025 TRPV2 in muscle satellite cells is crucial for skeletal muscle remodelling 888 EN Yanzhu Chen Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kimiaki Katanosaka Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University Makoto Shibuya Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yubing Dong Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Lidan Zhang Laboratory of Stem Cell Regeneration and Adaptation, Graduate School of Pharmaceutical Sciences, The University of Osaka Motoi Kanagawa Department of Cell Biology and Molecular Medicine, Ehime University Graduate School of Medicine So-ichiro Fukada Laboratory of Stem Cell Regeneration and Adaptation, Graduate School of Pharmaceutical Sciences, The University of Osaka Keiji Naruse Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Katanosaka Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Skeletal muscle remodelling relies on muscle stem cells (MuSCs) for regeneration after injury and hypertrophy in response to mechanical loading. However, the mechanisms that trigger MuSC activation and proliferation remain unclear. Transient receptor potential vanilloid 2 (TRPV2) ion channels respond to insulin-like growth factor-1 and mechanical stimuli to regulate the biological characteristics of various cells. Using a temporally inducible MuSC-specific conditional knockout (cKO) mouse, we show that TRPV2 regulates MuSC function and is essential for muscle remodelling. In cultured myofibre, MuSCs express TRPV2 and exhibit Ca2+ responses to the TRPV2 agonists 2-aminoethoxydiphenyl borate and probenecid, which are abolished upon TRPV2 deletion. TRPV2-deficient MuSCs exhibit reduced paired box 7 (Pax7) expression and impaired proliferation, suggesting TRPV2 is a factor that regulates the early stage of MuSC function. Myotube formation in MuSCs was enhanced by overexpression of TRPV2 and suppressed by TRPV2 deficiency, suggesting that TRPV2 is a factor that promotes myogenesis. Muscle-administered cardiotoxin promoted muscle regeneration and resulted in the appearance of numerous Pax7-positive MuSCs between myofibres. MuSC-specific TRPV2 cKO mice exhibit substantially impaired muscle regeneration after cardiotoxin-induced injury, drastically reducing Pax7-positive MuSCs between myofibres. In floxed mice, mechanical loading via synergist ablation induces hypertrophy and greatly increases the number of myonuclei per myofibre. In contrast, MuSC-specific TRPV2 cKO mice show no changes in myofibre thickness or nuclear number, either at baseline or after mechanical loading. Mechanical loading of floxed mice increased TRPV2+/Pax7+ double-positive MuSCs, but MuSC-specific TRPV2 cKO mice showed no change. Additionally, MuSCs exhibit Ca2+ responses to hypo-osmotic stimuli, which are suppressed by TRPV2 inhibitors and TRPV2 deletion, suggesting that MuSCs exhibit TRPV2-dependent mechanical responses. These results establish TRPV2 as a critical regulator of MuSC-mediated muscle remodelling, an important finding that may lead to therapeutic strategies for muscle repair and adaptation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1435-2451 411 1 2025 The impact of liver transection depth on surgical difficulty in robotic versus laparoscopic limited liver resection (TAKUMI-5) 22 EN Tomokazu Fuji Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kosei Takagi Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kazuya Yasui Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Atene Ito Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takeyoshi Nishiyama Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuo Nagai Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shohei Yokoyama Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Purpose Although robotic liver resection (RLR) has gained popularity worldwide, limited liver resection remains the mainstay of RLR. This study aimed to investigate the effect of parameters, including liver transection depth (LTD), on surgical difficulty in limited RLR compared with limited laparoscopic liver resection (LLR).<br> Methods This retrospective study included 105 patients who underwent limited RLR (n = 56) or LLR (n = 49) at our institution between January 2018 and December 2024. After comparing outcomes of RLR and LLR, multivariate analyses were performed to examine effect of LTD on surgical difficulty (defined as prolonged operative time). Moreover, outcomes stratified by LTD cut-off values were compared between the groups.<br> Results Median LTD was similar between groups (RLR vs. LLR: 2.6 vs. 2.6 cm, P = 0.77). LTD was significantly correlated with operative time for both procedures (RLR, R² = 0.07, P = 0.042; LLR, R² = 0.08, P = 0.046). Multivariate analyses demonstrated that LLR (odds ratio, 6.9; P < 0.001) and LTD (odds ratio, 2.0; P = 0.004) were significant risk factors of surgical difficulty. Among patients with deeper LTD (> 2.5 cm), the RLR group had significantly shorter operative time (145 vs. 231 min, P < 0.001), less blood loss (nil vs. 100 mL, P = 0.006), and a higher rate of textbook outcomes (76.7% vs. 42.3%, P = 0.01).<br> Conclusion This study investigated impact of LTD on surgical outcomes in patients who underwent limited RLR compared to those who underwent limited LLR. LTD may be a useful parameter for estimating surgical difficulty in limited RLR. Moreover, robotic surgery may be favorable for deeper and limited liver resections. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1435-2451 411 1 2025 Surgical outcomes and patient selection in nonagenarians with colon cancer: a comparative multi-institutional study of laparoscopic and open approaches 21 EN Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoe Takanaga Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Ryo Inada Department of Surgery, Kochi Health Sciences Center Toshiaki Toshima Department of Surgery, Kagawa Rosai Hospital Tsuyoshi Ohtani Department of Surgery, Saiseikai Okayama Hospital Ryosuke Yoshida Department of Surgery, Okayama Rosai Hospital Naoto Hori Department of Surgery, Tottori Municipal Hospital Kaoru Shigemitsu Department of Surgery, Tsuyama Chuo Hospital Sumiharu Yamamoto Department of Surgery, Okayama City Hospital Tetsushi Kubota Department of Surgery, Kobe Red Cross Hospital Yuka Okano Department of Surgery, Onomichi City Hospital Tetsuji Nobuhisa Department of Surgery, Himeji Red Cross Hospital Fumitaka Taniguchi Department of Surgery, National Hospital Organization Iwakuni Clinical Center Wataru Ishikawa Department of Surgery, Fukuyama City Hospital Tatsuo Matsuda Department of Surgery, Matsuda Hospital Tatsuo Umeoka Department of Surgery, Matsuyama City Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Setouchi Colorectal Neoplasm Registration study group collaborators Purpose The appropriate surgical approach for colon cancer (CC) in nonagenarian patients remains a subject of clinical debate. This study aimed to compare the short-term outcomes of laparoscopic (Lap) versus open (Open) surgery in patients aged ≥ 90 years with resectable colon cancer.<br> Methods This multi-institutional retrospective cohort study included oldest-old patientswith pathological Stage II/III CC who underwent elective surgery at 15 hospitals between 2011 and 2022. Patients with rectal cancer, Stage 0/I/IV disease, or emergency surgery were excluded. To address selection bias, inverse-probability-weighted regression adjustment and stabilized inverse probability of treatment weighting (sIPTW) were applied. The primary outcome was postoperative complications; secondary outcomes included overall survival (OS).<br> Results Median age was 92 years in both groups. Before adjustment, the Lap group had a higher proportion of female patients (p = 0.038) and lower ASA scores (p = 0.01). Laparoscopic surgery was associated with a significantly longer operative time (220 vs. 171 min, p = 0.046) but less intraoperative blood loss (10 vs. 78 mL, p < 0.01). Postoperative complication rates were comparable (Lap: 31.8%, Open: 33.8%), while the Lap group had a significantly shorter hospital stay (13 vs. 17 days, p < 0.01). D3 lymph node dissection was more frequently performed in the Lap group (p < 0.01). After sIPTW, overall survival did not differ significantly between groups (p = 0.61).<br> Conclusion Both laparoscopic and open surgery are feasible options for selected nonagenarians with colon cancer. Laparoscopic surgery may offer benefits in terms of reduced blood loss and shorter hospitalization, despite longer operative times. Careful patient selection considering frailty and comorbidities is essential in determining the most appropriate surgical approach. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2038-131X 2025 Early C-reactive protein as a predictive biomarker for postoperative complications following robot-assisted surgery for rectal cancer EN Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryusei Takahashi Department of Surgery, NHO Fukuyama Medical Center Hiroki Okabayashi Department of Surgery, NHO Fukuyama Medical Center Masashi Utsumi Department of Surgery, NHO Fukuyama Medical Center Hideaki Miyaso Department of Surgery, NHO Fukuyama Medical Center Ryohei Shoji 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 Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Masaru Inagaki Department of Surgery, NHO Fukuyama Medical Center This retrospective cohort study aimed to assess the predictive value of early postoperative C-reactive protein (CRP) levels for complications following robot-assisted rectal surgery (RARS) for rectal cancer. We analyzed data from 117 consecutive patients who underwent elective RARS at Okayama University Hospital between September 2020 and January 2025. Serum CRP levels were routinely measured preoperatively and on postoperative days (POD) 1 and 4. The primary outcome was the occurrence of any postoperative complication within 30 days, classified according to the Clavien–Dindo grading system. Postoperative complications were observed in 26 patients, representing 22.2% of the cohort. Univariate analysis revealed that several factors were significantly associated with complications, including older age, higher ASA score, neoadjuvant therapy, stoma creation, prolonged operative time, and elevated CRP levels on POD1 and POD4. Notably, multivariate logistic regression analysis identified POD1 CRP as a robust independent predictor of overall postoperative complications (adjusted odds ratio 0.77, 95% confidence interval (CI) [0.63–0.93], p < 0.01). In the ROC analysis, the AUC was 0.735 (bootstrap bias-corrected 95% CI 0.544–0.848). The optimal cutoff value of POD1 CRP was 5.63 mg/dl, at which Youden’s index, yielding a sensitivity of 0.615 and specificity of 0.868. In conclusion, early postoperative measurement of CRP on POD1 serves as a valuable and independent biomarker for predicting complications following RARS for rectal cancer. Incorporating POD1 CRP into postoperative surveillance may facilitate the early identification of high-risk patients, thereby facilitating timely interventions and ultimately improving surgical outcomes in this patient population. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Comparative efficacy of immune checkpoint inhibitor combination therapies by metastatic site in metastatic renal cell carcinoma 3303 EN Shingo Toyoda Department of Urology, Faculty of Medicine, Kindai University Lan Inoki Department of Urology, Faculty of Medicine, Kindai University Mamoru Hashimoto Department of Urology, Faculty of Medicine, Kindai University Wataru Fukuokaya Department of Urology, The Jikei University School of Medicine Keiichiro Mori Department of Urology, The Jikei University School of Medicine Shingo Nishimura Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ryoichi Maenosono Department of Urology, Osaka Medical and Pharmaceutical University Takehiro Iwata Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kensuke Bekku Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takuhisa Nukaya Department of Urology, Fujita-Health University School of Medicine Takafumi Yanagisawa Department of Urology, The Jikei University School of Medicine Takuya Tsujino Department of Urology, Osaka Medical and Pharmaceutical University Kazumasa Komura Department of Urology, Kawasaki University School of Medicine Kiyoshi Takahara Department of Urology, Fujita-Health University School of Medicine Teruo Inamoto Department of Urology, Hamamatsu University School of Medicine Haruhito Azuma Department of Urology, Osaka Medical and Pharmaceutical University Kazutoshi Fujita Department of Urology, Faculty of Medicine, Kindai University JK-FOOT study group Few studies have investigated the efficacy of immuno-oncology (IO) combinations at different metastatic sites in renal cell carcinoma (RCC). We evaluated the differential efficacy of IO–IO and IO–tyrosine kinase inhibitor (TKI) combinations by metastatic site in metastatic RCC (mRCC). This retrospective multicenter study by the JK-FOOT Study Group included 579 patients with intermediate- or poor-risk mRCC (per International Metastatic RCC Database Consortium criteria) treated with first-line IO combinations between September 2018 and December 2024. Metastatic sites were lymph nodes, lungs, bones, liver, brain, and others. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoint was objective response rate. Efficacy was compared between IO–IO and IO–TKI for each site. For lymph node (n = 36), lung (n = 132), or brain (n = 16) metastases, OS or PFS was not significantly different between IO–IO and IO–TKI. In bone metastases (n = 80), OS tended to favor IO–TKI (P = 0.053). In liver metastases (n = 22), OS was significantly longer with IO–TKI (P = 0.011). IO–TKI may be a more appropriate first-line option than IO–IO for mRCC with bone or liver metastases, while efficacy is similar for other sites. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Objective assessment of cesarean section suturing techniques using a uterine simulator 7456 EN Hikari Nakato Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Jota Maki 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 Keiichi Oishi 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 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 Masakazu Kato 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 Satoe Kirino 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 Cesarean wound healing is influenced by surgeon experience, suture type, and technique. This study utilized a simulation model to quantify these effects. Obstetricians–gynecologists and junior residents performed two-layer continuous suturing on uterine models, forming eight groups based on experience level (expert, novice), suture type (conventional, barbed), and technique (Albert–Lembert, layer-to-layer). The ideal wound condition was defined as that achieved by an expert using barbed sutures and the layer-to-layer technique. Wound characteristics were quantified and compared to this ideal. Experts using barbed sutures in Albert–Lembert suturing showed higher wound density but greater deformation and larger endometrial openings (both P < 0.01). Novices using barbed sutures in Albert–Lembert suturing showed similar wound density but significantly greater deformation and opening (both P < 0.01). Novices using conventional sutures in layer-to-layer suturing showed the lowest wound density and longest suturing time (both P < 0.01). Notably, novices using barbed sutures achieved wound characteristics comparable to experts using conventional sutures in Albert–Lembert suturing and results closer to the ideal in layer-to-layer suturing. These findings establish a quantifiable standard for cesarean suturing and suggest that optimizing suture types and techniques may help compensate for differences in surgical expertise. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1863-9941 52 1 2026 Preferential sacral fracture sites in fragility fractures of the pelvis type IVb and comparison of internal fixation methods: CT-based morphological mapping and finite element analysis 72 EN Shuichi Naniwa Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masanori Yorimitsu Department of Musculoskeletal Traumatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Tsubasa Hasegawa Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teruhiko Ando Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuichiro Okuda Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shiro Fukuoka Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital Yusuke Mochizuki Department of Emergency Health Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuaki Yamakawa Department of Orthopaedic Surgery, Kochi Health Sciences Center Ryuichi Nakahara Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shiro Hanakawa Department of Orthopaedic Surgery, Okayama Saidaiji Hospital Toshifumi Ozaki Department of Orthopedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose Fragility fractures of the pelvis (FFP) classified as Rommens-Hoffman type IVb are associated with spinopelvic dissociation and are generally considered to require surgical intervention. This study aimed to clarify the localization patterns of FFP type IVb and compare the biomechanical stability of different internal fixation techniques.<br> Methods In this retrospective study, morphologic mapping of sacral fracture lines was performed in 36 patients with FFP type IVb. Based on the mapping results, a finite element (FE) model of FFP type IVb was developed to evaluate the biomechanical stability of ilio-sacral screw (ISS) fixation, trans-sacral screw (TSS) fixation, spinopelvic fixation (SPF; On each side, L5 pedicle screw was connected to two iliac screws with a rod, and the bilateral constructs were linked using a cross-connector.), and bilateral triangular fixation (one TSS at S1 combined with SPF mentioned above) using finite element analysis (FEA).<br> Results Morphologic mapping showed that the sacrum fracture transverse line tended to pass between the S1-2 transverse lines. Although bilateral triangular fixation and SPF provided the highest stability in both U-type and H-type fractures, a TSS for U-type and two TSSs for H-type also demonstrated comparable levels of stability. ISS-based methods showed greater displacements.<br> Conclusion TSS-based fixation may provide stability comparable to bilateral triangular fixation and SPF in FFP type IVb, with less invasiveness when anatomy permits. Further studies are needed to optimize treatment strategies for this complex injury. 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.<br> 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.<br> 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).<br> 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.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2261 25 1 2025 Prognostic value of right atrial strain in patients with chronic heart failure 908 EN Rie Nakayama Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Yoichi Takaya Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Mitsutaka Nakashima Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Takahiro Nishihara Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Norihisa Toh Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Miyoshi Toru Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Kazufumi Nakamura Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Shinsuke Yuasa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Aims Right ventricular dysfunction is a well-established prognostic marker in patients with heart failure (HF). However, the prognostic significance of right atrial (RA) function remains unclear. Given its sensitivity to systemic congestion, RA function may provide additional insights into HF disease progression and management. This study aimed to investigate whether RA reservoir function serves as an independent prognostic indicator in patients with chronic HF.<br> Methods A total of 613 patients with chronic HF and a left ventricular (LV) ejection fraction of less than 50% who underwent echocardiographic assessment at Okayama University Hospital between January 2018 and March 2023 were included (median age: 68 (58–76) years; 69% male). RA reservoir function was quantified using two-dimensional speckle-tracking echocardiography. The primary endpoint was cardiovascular death or HF-related hospitalization. Kaplan–Meier survival analysis was performed to examine the association between RA reservoir function and clinical outcomes.<br> Results During a median follow-up period of 41 months (range: 12–91 months), 119 patients experienced cardiac events. Compared with event-free patients, those with cardiac events exhibited a significantly larger RA maximum volume index (38 mL/m2 vs. 31 mL/m2, P < 0.001) and a significantly lower RA reservoir longitudinal strain (RASr) (17% vs. 22%, P < 0.001). Kaplan–Meier analysis demonstrated that patients with RASr ≤ 20% had significantly poorer event-free survival than those with RASr > 20%, even without RA volume enlargement (log-rank test, P < 0.001). Multivariate Cox regression analysis identified RASr as an independent predictor of cardiac events (hazard ratio: 0.95, 95% confidence interval: 0.93 to 0.97, P < 0.001).<br> Conclusions In patients who experienced adverse cardiac events, a reduced RASr and an increased RA maximum volume were observed. Furthermore, a reduced RASr was independently associated with an increased risk of cardiovascular death and HF-related hospitalization in patients with chronic HF and LV dysfunction. These findings indicate that RASr may serve as a valuable prognostic marker for the risk stratification and management of chronic HF. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1364-6753 27 1 2026 Compound heterozygosity of a novel missense variant and exonic deletion in hypomyelinating leukodystrophy 15 16 EN Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology Kenta Orimo Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology Kunihiro Ueda Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology Tomonari Seki Department of Neurology, Tokyo Teishin Hospital Yasushi Shiio Department of Neurology, Tokyo Teishin Hospital Jun Mitsui Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Harushi Mori Department of Radiology, School of Medicine, Jichi Medical University, 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, Tokyo, Japan Department of Neurology Hypomyelinating leukodystrophy 15 (HLD15) results from biallelic pathogenic variants in EPRS1, but exonic deletions have not been reported. We describe a 40-year-old woman with mild intellectual disability, ataxia, dystonia, and MRI showing hypomyelination. Whole-exome sequencing identified a heterozygous missense variant in the prolyl-tRNA synthetase domain of EPRS1 (c.3430 C > G; p.Leu1144Val, NM_004446.3), without second variant. Whole-genome sequencing revealed a heterozygous 220-bp deletion spanning exon 15 (c.1743-30_1932del), and segregation analysis confirmed compound heterozygosity. RT-PCR from lymphoblastoid cells demonstrated exon-15 skipping leading to a frameshift (p.Asn582Serfs*10) and nonsense-mediated decay, leaving predominant expression of the paternally inherited missense allele. These findings support loss-of-function for the deletion and classify c.3430 C > G as likely pathogenic under ACMG/AMP criteria (PM1, PM2, PM3, PP3). This case represents the first exonic deletion reported in EPRS1. The relatively mild, adult-onset phenotype broadens both mutational and clinical spectra of HLD15 and highlights the importance of structural-variant anal 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.

Springer Science and Business Media LLC Acta Medica Okayama 1546-0096 23 1 2025 Comparison of clinical practices during the transitional and young adult phases between patients with oligoarticular/polyarticular juvenile idiopathic arthritis and those with rheumatoid arthritis in Japan 120 EN Sho Mori Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine Kosuke Shabana Department of Pediatrics, Osaka Medical and Pharmaceutical University Toshihiro Matsui Department of Rheumatology Research, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital Tomo Nozawa Department of Pediatrics, Graduate School of Medicine, Yokohama City University Yuko Sugita Department of Pediatrics, Osaka Medical and Pharmaceutical University Minako Tomiita Department of Allergy and Rheumatology, Chiba Children’s Hospital Yasuo Nakagishi Department of Pediatric Rheumatology, Hyogo Prefectural Kobe Children’s Hospital Yuichi Yamasaki Department of Pediatrics, Kagoshima University Hospital Hiroaki Umebayashi Department of General Pediatrics, Miyagi Children’s Hospital Masato Yashiro Department of Pediatrics, Okayama University Hospital Naomi Iwata Department of Infection and Immunology, Allergy and Immunology Center, Aichi Children’s Health and Medical Center Junko Yasumura Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences Hiroyuki Wakiguchi Department of Pediatrics, Yamaguchi University Graduate School of Medicine Takeshi Yamamoto Department of Pediatrics, Chiba University Graduate School of Medicine Shunichiro Takezaki Department of Pediatrics, Faculty of Medicinea and Graduate School of Medicine, Hokkaido University Yuka Okura Center for Pediatric Allergy and Rheumatology, KKR Sapporo Medical Center Tadafumi Yokoyama Department of Pediatrics, Kanazawa University Masaki Shimizu Department of Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Masahiro Hirayama Department of Pediatrics, Mie University Graduate School of Medicine Shigeto Tohma Department of Rheumatology, National Hospital Organization Tokyo National Hospital Nami Okamoto Department of Pediatrics, Osaka Medical and Pharmaceutical University Masaaki Mori Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine Background Juvenile idiopathic arthritis (JIA) is a chronic inflammatory condition that frequently persists into adulthood, posing long-term challenges in disease control and quality of life. However, clinical management during the transitional and young adult phases remains insufficiently characterized, especially in comparison with adult-onset rheumatoid arthritis (RA). This study aimed to compare disease activity, medication use, and treatment practices between patients with oligoarticular/polyarticular JIA and those with RA, focusing on individuals aged 16–30 years.<br> Methods Data were derived from two nationwide multicenter databases in Japan―NinJa (National Database of Rheumatic Diseases in Japan) for RA and CoNinJa (a pediatric counterpart of NinJa) for JIA. A total of 176 JIA and 152 RA patients, all aged 16–30 years, were analyzed. Clinical parameters, disease activity indices, and medication profiles were compared using the Mann–Whitney U test and Fisher’s exact test.<br> Results Compared to RA patients, JIA patients demonstrated significantly lower disease activity (median SDAI 0.6 vs. 2.4) and higher remission rates, particularly Boolean remission (70% vs. 44%) (p < 0.001). MTX usage was less frequent in JIA (49% vs. 68%, p < 0.001), whereas biologic use was notably more common (69% vs. 38%, p < 0.001), with 31% involving off-label prescriptions. Among patients in CDAI remission, biologic monotherapy was observed more frequently in JIA (29% vs. 7%, p < 0.001). Discontinuation of MTX was most commonly attributed to disease improvement (58%) or gastrointestinal intolerance (nausea, 29%). Subcutaneous tocilizumab, though unapproved for JIA in Japan, had the lowest discontinuation rate (4%), suggesting favorable tolerability.<br> Conclusions Despite an overlap in age, patients with JIA and RA exhibit distinct disease characteristics and therapeutic patterns. These differences underscore the need to expand approved treatment options for JIA, promote equitable access to biologics, and strengthen transitional care frameworks. Further research is warranted to explore long-term outcomes, reproductive health considerations, and socioeconomic barriers that influence treatment continuity in young adults with childhood-onset arthritis. 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.<br> 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.<br> 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).<br> 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.

岡山大学文学部 Acta Medica Okayama 0285-4864 78 2025 広島市方言におけるアクセントの継承と変容（1）─ 1 拍・2 拍・3 拍名詞のアクセントの世代的動態 ─ 39 50 EN Yasue NAKATO 10.18926/okadai-bun-kiyou/70219 No potential conflict of interest relevant to this article was reported.

岡山大学文学部 Acta Medica Okayama 0285-4864 78 2025 非大都市圏小規模自治体の持続的発展と地域的対応の特徴 1 11 EN Hirofumi KITAGAWA 10.18926/okadai-bun-kiyou/70216 No potential conflict of interest relevant to this article was reported.

岡山大学文学部 Acta Medica Okayama 0285-4864 78 2025 表紙・目次 EN No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1556-0864 20 12 2025 Final Analysis Results and Patient-Reported Outcomes From DESTINY-Lung02―A Dose-Blinded, Randomized, Phase 2 Study of Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic NSCLC 1814 1828 EN Pasi A. Jänne Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute Yasushi Goto Department of Thoracic Oncology, National Cancer Central Hospital Toshio Kubo Center for Clinical Oncology, Okayama University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Sang-We Kim Oncology Department, Asan Medical Center, Seoul, and University of Ulsan College of Medicine, Ulsan David Planchard Department of Medical Oncology, Thoracic Cancer Group, Gustave Roussy, and Faculty of Medicine, Paris-Saclay University Myung-Ju Ahn Department of Hematology and Oncology, Samsung Medical Center Sungkyunkwan, and University School of Medicine Egbert Smit Department of Pulmonary Diseases, Leiden University Medical Center Adrianus Johannes de Langen Department of Thoracic Oncology, Netherlands Cancer Institute Maurice Pérol Department of Medical Oncology, Léon Berard Centre Elvire Pons-Tostivint Centre Hospitalier Universitaire Nantes, Nantes University Silvia Novello Department of Oncology, University of Turin, Turin, and Azienda Ospedaliero-Universitaria San Luigi Gonzaga Hidetoshi Hayashi Department of Medical Oncology, Kindai University Hospital Junichi Shimizu Department of Thoracic Oncology, Aichi Cancer Center Hospital Dong-Wan Kim Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital Kaline Pereira Daiichi Sankyo Fu-Chih Cheng Daiichi Sankyo Ayumi Taguchi Daiichi Sankyo Yingkai Cheng Daiichi Sankyo Kyle Dunton Daiichi Sankyo UK Ahmed Ali Daiichi Sankyo Europe GmbH Koichi Goto Department of Thoracic Oncology, National Cancer Center Hospital East Introduction: Trastuzumab deruxtecan (T-DXd) demonstrated strong and durable responses in patients with previously treated HER2 (ERBB2) mutant (HER2m) metastatic NSCLC (mNSCLC) in the DESTINY-Lung02 primary analysis (December 23, 2022, data cutoff). This final analysis evaluated T-DXd efficacy and safety after 8 additional months of follow-up, including clinically relevant subgroups and patient-reported outcomes.<br> Methods: DESTINY-Lung02 was a randomized, dose-blinded, multicenter, phase 2 trial. Patients with previously treated HER2m mNSCLC were randomized 2:1 to receive T-DXd 5.4 or 6.4 mg/kg once every 3 weeks. Primary end point was confirmed objective response rate by blinded independent central review.<br> Results: As of August 25, 2023, 102 and 50 patients had received T-DXd 5.4 or 6.4 mg/kg, respectively. Median follow-up (Q1–Q3) was 15.8 (8.2–20.7) months and 16.5 (9.4–20.8) months, respectively. Confirmed objective response rate (95% confidence interval) was 50.0% (51/102; 39.9%–60.1%) and 56.0% (28/50; 41.3%–70.0%), respectively. Safety profile was acceptable and generally manageable. Accordingly, median treatment duration (Q1–Q3) was 7.7 (3.7–14.4) months and 8.3 (2.8–13.1) months; drug-related grade 3 or higher treatment-emergent adverse events occurred in 39.6% (40/101) and 60.0% (30/50), with nausea most common (67.3% [68/101], 82.0% [41/50]). Adjudicated drug-related interstitial lung disease occurred in 14.9% (15/101) and 32.0% (16/50), mostly grade 1 or 2 with one grade 5 in each arm. Health-related quality of life was preserved for the duration of T-DXd treatment while sample size was sufficient for analysis, with no adverse effects on health-related quality of life observed at either dose.<br> Conclusions: T-DXd demonstrated strong and durable responses at both doses, with no clinically significant changes in toxicity. The approved 5.4-mg/kg dose demonstrated a more favorable benefit-risk profile, including lower adjudicated drug-related interstitial lung disease incidence.<br> ClinicalTrials.gov identifier: NCT04644237 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 &amp; Pharmaceutical Science, Okayama University Takehiro Tanaka Department of Pathology and Oncology, Graduate School of Medicine, Dentistry &amp; Pharmaceutical Science, Okayama University Riri Mishima Department of Pathology and Oncology, Graduate School of Medicine, Dentistry &amp; 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 &amp; 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.<br> 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.<br> 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.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 191 2026 青年の肯定的自己理解を促す強み介入の実践報告 ― 発達支持的教育相談によるアプローチを通して ― 187 196 EN Tsuguyuki IZUMI Faculty of Education, Okayama University 10.18926/bgeou/70207 　本研究は，発達支持的教育相談として実施した強み認識授業が，青年の自己の強み選択の難易度に及ぼす影響を探索的に検討したものである。研究１では中国地方の公立中学校423名を対象にオンラインで，研究２では専門学校学生86名，大学生93名を対象に対面で，強み認識授業を実施し，授業後に，自己の強み選択の難易度を測定した。その結果，すべての群の強み選択の難易度の評価は，平野(2019)と比較して「容易である」との回答傾向を示した(Mdn = ７)。また，３群の強み選択の難易度の分布に統計的な有意差は認められなかった(p = .222)。この知見は，本授業が対象者の発達段階や実施形式(オンライン・対面)に関わらず，普遍的に強み特定を支援する機能を持つ可能性を示唆する。最後に，この知見をもとに，学校現場での教育相談の新たな展開を提言した。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 191 2026 デジタルメディア・デジタルデバイスの自律的な使用に向けて（１） ― 自己制御能力とインターネット依存傾向に関する研究の概観から ― 169 175 EN Motoko MIYAKE Faculty of Education, Okayama University 10.18926/bgeou/70205 　デジタルメディア・デジタルデバイスの使用において，使用開始年齢の低年齢化・長時間利用の実態が指摘され，低年齢の子どもについても依存等の問題が注目されつつある。本報告では，子ども自身に，デジタルメディア・デジタルデバイスと適切に付き合う力を育てることの必要性を重視する立場から，インターネット依存傾向の抑制要因の１つに挙げられる自己制御能力に着目し，両者の関連についての本邦における研究を概観する。そして，子どもの自己制御の発達過程，自己制御の発達における促進要因・抑制要因を整理した上で，インターネット依存の予防のために子どもの自己制御の発達の観点から得られる示唆について検討した。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 191 2026 Character Education の動向と児童の特性を生かした教育的介入の可能性について ― Character Education と Character Strengths Education を区別して ― 63 77 EN Minglu LI The Joint Graduate School in Science of School Education, Hyogo University of Teacher Education Tazuko AOKI Faculty of Education, Okayama University 10.18926/bgeou/70196 　児童の幸福や心理的 well-being を高める研究の1つが，よい character の育成を目指す教育研究である。Lavy（2020）は，これには2つの流れがあるとする。１つが character education，もう１つは character strengths education である。本稿では，まずこの2つの特徴について解説して世界の流れを示し，次にポジティブ心理学に基づく character strengths education の限界点を指摘した。具体的には，その原典となるVIA-IS（Peterson & Seligman, 2004）について，東アジアにおける強みと well-being の関連研究がほとんど成されていないこと，加えて児童期の教育的介入の成果がほとんど見られないことを指摘した。これらの検討を通して，児童期の認知特性や発達段階に応じた，児童の負荷の少ない身体活動量，習慣形成の視点で character の育成を目指す教育的介入の可能性について議論した。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 191 2026 教職員研修の高度化に果たす大学の役割と課題 ― NITS 岡山大学センターの活動を通して ― 1 16 EN Atsushi TAKASE Faculty of Education, Okayama University Akiko TSURUMI Okayama University Kindergarten Chiyo KUROSUMI Okayama University Kindergarten Tetsuo KIYOTA Faculty of Education, Okayama University Yoshihiko INADA Faculty of Education, Okayama University Ai MATSUURA Faculty of Education, Okayama University Kouji MIYAMOTO Faculty of Education, Okayama University Mutsumi MATSUEDA Faculty of Education, Okayama University Aiko TSUSHIMA Faculty of Education, Okayama University Yoshio MIYAZAKI Faculty of Education, Okayama University Toshiya TAKEMOTO Okayama University School for Special Needs Education Yoko SAWATANI Okayama University School for Special Needs Education Kazuaki KAJII Faculty of Education, Okayama University Makiko KANAGAWA Faculty of Education, Okayama University 10.18926/bgeou/70192 　本論文では，専門職としての教職員の学びを保障する研修のあり方を検討し，とくに大学が果たす役割と課題について考察する。教職員の学びは教育委員会での研修，勤務校園での研修，教職大学院での学修，研究団体での研修などにおいて展開される。大学が開発・実施する研修はこれらとどう関連し，どのような特色をもつか。独立行政法人教職員支援機構（以下，NITS）岡山大学センターの活動を通して検討する。そして，大学は教職員の学びのニーズに応える側にあるだけでなく，教職員の学びを再構成し，自律的協働的な学びを支援・促進していく側としての役割を果たすものであることを考察する。また，大学おけるアウトカム重視の研修開発の必要性を指摘し，今後の取組の課題として示す。 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 191 2026 表紙・目次 EN No potential conflict of interest relevant to this article was reported.

American Association for Cancer Research (AACR) Acta Medica Okayama 2767-9764 6 2 2026 Clinical Characteristics and Spatial Transcriptome Analysis of Non–Small Cell Lung Cancers Exhibiting Early Alectinib Resistance: A Retrospective OLCSG Study 284 293 EN Tadahiro Kuribayashi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Go Makimoto Department of Respiratory Medicine, Okayama University Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Hirofumi Inoue Center for Comprehensive Genomic Medicine, Okayama University Hospital Toshihide Yokoyama Department of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital Shoichi Kuyama Department of Respiratory Medicine, NHO Iwakuni Clinical Center Yuka Kato Department of Thoracic Oncology and Medicine, National Hospital Organization, Shikoku Cancer Center Kenichiro Kudo Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center Naokatsu Horita Department of Respiratory Medicine, Kure Kyosai Hospital Hiroe Kayatani Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Masaaki Inoue Department of Chest Surgery, Shimonoseki City Hospital Keisuke Sugimoto Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Togashi Department of Respiratory Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Some anaplastic lymphoma kinase (ALK) gene rearrangement–positive lung cancers show early resistance, within 3 months, to alectinib. This study investigated the clinical and molecular characteristics of these patients. We analyzed patients with unresectable stage III/IV disease without indications for radical radiotherapy and recurrent ALK-positive lung cancer who received alectinib as the primary ALK tyrosine kinase inhibitor between 2013 and 2021 at nine hospitals. In total, 103 patients were included. The median age was 65 years; 44 were male and 22 had brain metastases. The median progression-free survival and overall survival (OS) were 28.7 and 80.6 months. Nineteen patients treated for ≤3 months and 84 treated for >3 months were categorized into the early resistance and responder groups, respectively. The early resistance group had significantly shorter OS (8.4 months vs. not estimable, P < 0.001) and was significantly more likely to have brain metastases (42% vs. 17%, P = 0.027). They also showed elevated inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR). Univariate analysis identified brain metastases and high NLR as significant predictors of early resistance. Spatial transcriptome analysis and immunohistochemical staining revealed upregulation of annexin A1 (ANXA1), a calcium-dependent phospholipid-binding protein involved in inflammation and cancer progression, in the early resistance group. Interleukin 6 stimulation, prompted by elevated inflammatory markers, increased ANXA1 expression and reduced alectinib sensitivity. Knockdown of ANXA1 improved alectinib sensitivity in alectinib-resistant cells. In conclusion, brain metastases and high NLR are associated with early resistance. ANXA1 may play an important role in mediating early resistance. New treatment options for the early resistance group are required. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1345-2630 2026 Tabtoxin biosynthetic gene cluster in Pseudomonas syringae pv. tabaci 6605 genomic island 1 (GI-1Pta6605) is required for severe disease symptoms EN Kotomi Kunishi The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Norika Fujisawa The Graduate School of Environmental, Life, Natural Science and Technology, 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 One of the genomic islands in Pseudomonas syringae pv. tabaci 6605 (GI-1Pta6605) has been identified as a pathogenicity island required for virulence because the deletion almost completely eliminated disease symptoms in inoculation tests at 4 × 105 CFU/ml. GI-1Pta6605 contains four cargo regions (CRs) named CR-1 to CR-4. The ∆CR-4 mutant did not produce tabtoxin like ∆GI-1 and disease symptoms did not develop in tobacco. However, it grew, although to a lesser extent than the wild-type strain. These results indicate that the tabtoxin biosynthetic gene cluster in GI-1 is required for virulence but not for establishment of compatibility. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0956-7135 183 2026 Monitoring postharvest water loss in eggplants (Solanum melongena L.) using UV-induced fluorescence imaging and multivariate analysis 111902 EN Vincent Rotich Laboratory of Biosensing Engineering, Graduate School of Agriculture, Kyoto University Tianqi Gao Laboratory of Biosensing Engineering, Graduate School of Agriculture, Kyoto University Panintorn Prempree Laboratory of Biosensing Engineering, Graduate School of Agriculture, Kyoto University Takahiro Hayashi Laboratory of Biosensing Engineering, Graduate School of Agriculture, Kyoto University Kazuhiko Namba Faculty of Environmental, Life, Natural Science and Technology, Okayama University Mitsuji Monta Faculty of Environmental, Life, Natural Science and Technology, Okayama University Motomi Nishimoto Technology and Innovation Center, Daikin Industries, Ltd. Naoshi Kondo Laboratory of Biosensing Engineering, Graduate School of Agriculture, Kyoto University Eggplant (Solanum melongena L.) is susceptible to significant postharvest losses primarily due to water loss during storage, which affects market quality by causing texture and glossiness degradation. We investigated whether UV-induced fluorescence imaging and EEM (Excitation-Emission Matrix) fluorescence spectroscopy can non-destructively monitor WL under four storage regimes (10 °C/95 % RH, 20 °C/95 % RH, 20 °C/75 % RH, 10 °C/75 % RH). EEMs exhibited three regions; a 365/420 nm blue emission increased most under warm, low-humidity storage and is consistent with phenolic/lignin-related fluorescence. Side-view fluorescence (FL) images showed progressive blue-white emission and surface textural changes that tracked gravimetric water loss (WL). A PLSR model using combined color and texture features from FL and reflectance (CL) images achieved R2CV = 0.88 (RMSECV = 3.47 %) with only six features. To test a minimal predictor, we fit an Analysis of Covariance (ANCOVA) using Day-1 FL MeanBlue as a covariate and storage category as a factor with Leave One Out Cross-validation (LOOCV); this forecasted cumulative WL with R2LOOCV = 0.92 and MAE = 1.88 %. Importantly, this ANCOVA model using Day-1 blue-band fluorescence as a covariate was predictive only under 20 °C/75 % RH; under the other conditions, its contribution was weak. Linear Discriminant Analysis (LDA) and Support Vector Machine (SVM) models achieved accuracies of 94.4 % and 85.2 %, respectively, in differentiating storage conditions. These results support low-cost FL imaging as a practical tool to monitor WL and storage stress. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2752-6542 5 1 2025 Chloroplast heat shock protein cpHsc70-1 interacts with thylakoid membrane remodeling protein VIPP1 C-terminal tail and controls VIPP1 oligomer assembly pgaf393 EN Di Li Institute of Plant Science and Resources, Okayama University Sarah Wanjiru Gachie Institute of Plant Science and Resources, Okayama University Shin-ichiro Ozawa Institute of Plant Science and Resources, Okayama University Martin Scholz Institute of Plant Biology and Biotechnology, University of Münster Michael Hippler Institute of Plant Science and Resources, Okayama University Wataru Sakamoto Institute of Plant Science and Resources, Okayama University Oxygenic photosynthetic organisms depend on the thylakoid membranes (TMs) for light-driven energy conversion. Recent studies on TM homeostasis (thylakostasis) have highlighted the essential role of the TM remodeling protein vesicle-inducing protein in plastid 1 (VIPP1). As a member of the endosomal sorting complexes required for transport-III (ESCRT-III)/phage shock protein A (PspA)/VIPP1 superfamily, VIPP1 forms large ring- and filament-like homo-oligomeric structures that exhibit a membrane remodeling activity. The oligomerization status was proposed to be modulated by the intrinsically disordered C-terminal tail (Vc), whereas its functional role remained unclear. Notably, this Vc region is conserved not only in photosynthetic VIPP1 but also in the PspA proteins of extremophilic species, implicating its role in membrane stress responses. To investigate the role of the Vc region in VIPP1 assembly, we performed coimmunoprecipitation assays in Arabidopsis chloroplasts and identified chloroplast-localized HSP70 proteins (cpHsc70) as major interactors. Among the two isoforms, cpHsc70-1 was found to be specifically required for modulating VIPP1 oligomeric assembly and dynamics in response to heat stress. Genetic analyses revealed that cpHsc70-1 facilitates the disassembly of VIPP1 oligomers, similarly to Vps4 ATPase in ESCRT-III; loss of either the Vc region or cpHsc70-1-impaired VIPP1 disassembly, resulting in more static oligomeric structures. Furthermore, cpHsc70-1 exhibited a broader role in chloroplast proteostasis, as the cphsc70-1 mutant showed impaired accumulation of green fluorescent protein (GFP)-fusion proteins. Together, our findings uncover a crucial crosstalk between proteostasis and thylakostasis in chloroplasts, coordinated by cpHsc70-1 and VIPP1 in response to membrane stress. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Calcium ions play a critical role in calcification of Corynebacterium matruchotii 4591 EN Naoko Ohara Department of Operative Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Midori Ogawa Department of Microbiology, School of Medicine, University of Occupational and Environmental Health 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 Serina Ono Department of Operative Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mitsumasa Saito Department of Microbiology, School of Medicine, University of Occupational and Environmental Health Naoya Ohara Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Dental calculus is a hardened deposit composed of calcium phosphate precipitated within dental plaque. While the involvement of dental calculus in the progression of periodontal disease is well established, many aspects of its formation process remain poorly understood. In this study, we focused on Corynebacterium matruchotii, a key bacterium involved in dental calculus formation, and investigated the role of calcium ions in calcification, as well as the associated internal and external changes in the bacterium through long-term observation. In the absence of calcium ions, no intracellular calcification was observed, and the lipid bilayer with the formation of holes in bacterial body was evident. In contrast, in the presence of calcium ions, lipid bilayer remained intact, and intracellular needle- and plate- like crystals were formed. Furthermore, calcified C. matruchotii showed increased flocculation compared to non-calcified C. matruchotii. These results indicate that the influx of calcium ions is essential for intracellular calcification. Calcium ions entry appears to reinforce the integrity of the lipid bilayer, providing a stable intracellular environment conductive to calcification. Moreover, calcified C. matruchotii may contribute to the nucleation of dental calculus by forming aggregates composed of both bacterial components and calcified material. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1123-6337 29 1 2025 Safety and feasibility of D3 lymph node dissection in oldest-old patients undergoing colorectal cancer surgery: a multi-institutional, retrospective analysis 146 EN R. Inada Department of Surgery, Kochi Health Sciences Center F. Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences T. Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital S. Takanaga Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences T. Toshima Department of Surgery, Kagawa Rosai Hospital T. Ohtani Department of Surgery, Saiseikai Okayama Hospital R. Yoshida Department of Surgery, Okayama Rosai Hospital N. Hori Department of Surgery, Tottori Municipal Hospital K. Shigemitsu Department of Surgery, Tsuyama Chuo Hospital S. Yamamoto Department of Surgery, Okayama City Hospital T. Kubota Department of Surgery, Kobe Red Cross Hospital Y. Okano Department of Surgery, Onomichi City Hospital T. Nobuhisa Department of Surgery, Himeji Red Cross Hospital F. Taniguchi Department of Surgery, National Hospital Organization Iwakuni Clinical Center W. Ishikawa Department of Surgery, Fukuyama City Hospital R. Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences T. Matsuda Department of Surgery, Matsuda Hospital T. Umeoka Department of Surgery, Matsuyama City Hospital T. Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Setouchi Colorectal Neoplasm Registration Study Group Collaborators Background Colorectal cancer (CRC) is a significant health burden, with lymph node dissection (LND) playing a critical role in staging and guiding treatment. However, the optimal extent of LND for the oldest-old population (aged ≥ 90 years) remains undefined because of insufficient targeted clinical data. This study aimed to compare the short-term outcomes of D3 versus non-D3 LND in Stage II–III CRC in oldest-old patients.<br> Methods This retrospective cohort study utilized data from the Setouchi Colorectal Neoplasm Registration database, including 282 oldest-old patients with CRC treated between 2011 and 2022. Patients were stratified into D3 and non-D3 LND groups, with inverse-probability-weighted regression adjustment implemented to address potential confounding factors. Postoperative complications and hospital stays were analyzed using regression models and descriptive statistics.<br> Results D3 LND resulted in significantly higher lymph node harvests in both Stage II and Stage III patients (p < 0.01). There were no significant differences in overall or major postoperative complications between D3 and non-D3 groups. Hospital stays were comparable for Stage II patients but shorter for Stage III patients in the D3 group (p < 0.01). Complication rates ranged from 28% to 47.7%, with surgical site infections and pneumonia being the most common.<br> Conclusions D3 LND can be safely performed in oldest-old patients with CRC without increasing postoperative complications or extending hospital stays. These findings support the feasibility of extensive LND in this age gr No potential conflict of interest relevant to this article was reported.

Japanese Society for Horticultural Science Acta Medica Okayama 2189-0102 95 1 2026 Comparison of Fruit Development, Ripening, and Transcriptome Dynamics in Taiwanese and Japanese Cultivars of Japanese Apricot (Prunus mume Sieb. et Zucc.) 10 20 EN Tomoaki Kashiwamoto Graduate School of Environmental and Life Science, Okayama University Takashi Kawai Graduate School of Environmental and Life Science, Okayama University Takaaki Oe Japanese Apricot Laboratory, Wakayama Fruit Tree Experiment Station Koji Numaguchi Japanese Apricot Laboratory, Wakayama Fruit Tree Experiment Station Yuto Kitamura Faculty of Agriculture, Setsunan University Yasutaka Kubo Graduate School of Environmental and Life Science, Okayama University Fumio Fukuda Graduate School of Environmental and Life Science, Okayama University Koichiro Ushijima Graduate School of Environmental and Life Science, Okayama University In this study, we compared changes in traits associated with fruit development and ripening in Taiwanese and Japanese cultivars of Japanese apricot (Prunus mume Sieb. et Zucc.). We also analyzed transcriptome profiles to comprehensively examine different fruit development and ripening patterns between the two groups in terms of fruit characteristics and gene expression. Early fruit development in Taiwanese cultivars ‘ST’ and ‘Ellching’ and the Japanese cultivar ‘Hakuo’ was ahead of that in other three Japanese cultivars (P1). From late April to early May, around the stone-hardening stage, the developmental differences decreased to the same level. Thereafter, Japanese cultivars showed rapid growth, whereas Taiwanese cultivars showed slower growth, reversing the developmental differences between these lines (P2). Ethylene production was not detected until the full ripening stage and was detected for the first time at this stage in five cultivars, except for ‘Ellching’ (P3). In contrast, no ethylene production was observed during the entire duration of fruit development in ‘Ellching’. A multidimensional scaling plot showed that the overall transcriptome profile changed according to the three stages (P1–P3) of fruit development and ripening. At P1, gene ontologies (GOs) related to cell division, such as the cell cycle and regulation of cyclin-dependent protein serine/threonine kinase activity, were enriched for differentially expressed genes downregulated in Taiwanese cultivars as compared with their expression in Japanese cultivars. At P2, GOs related to fruit development were not enriched, but some genes related to phytohormones, such as auxin, abscisic acid, and cytokinin, which are associated with fruit development and ripening, were differentially expressed. At P3, the expression of genes such as ACS, ACO, and PG, which are involved in ethylene biosynthesis, increased in response to increased ethylene production, but not in ‘Ellching’, which showed no ethylene production. Expression analysis of 115 NAC (NAM-ATAF1/2-CUC2) family genes, which are related to fruit ripening and ripening date in other fruit species, in the ‘Ellching’ genome revealed changes in expression of NAC056 and NAC073 corresponding to fruit development and ripening in Taiwanese and Japanese cultivars. We discuss the differences in fruit development and ripening behaviors between Taiwanese and Japanese cultivars in terms of physiological and transcriptome changes. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1746-6148 22 1 2026 Genetic and phenotypic identities of Staphylococcus coagulans isolated from pustules of dogs with superficial bacterial folliculitis 98 EN Takafumi Osumi Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology Yuuki Shinomiya Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology Thamonwan Wanganuttara Department of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ichiro Imanishi Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai Yotaro Shimazaki Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology Keita Iyori 1sec Co. Ltd. Yoichi Toyoda 1sec Co. Ltd. Kaori Ide Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Nishifuji Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology Background Staphylococcus coagulans, formerly called Staphylococcus schleiferi subsp. coagulans is the second most common isolate from skin lesions of dogs with superficial bacterial folliculitis (SBF). However, the clinical significance of S. coagulans in pustules of canine SBF remains uncertain. This study aimed to investigate the prevalence and genotypic and phenotypic diversity of S. coagulans isolated from pustules in two dogs with SBF.<br> Results Two dogs with SBF were included in this study. S. schleiferi/coagulans was isolated as the sole organism from three pustules in case #1, whereas it coexisted with S. pseudintermedius in two of seven pustules in case #2. S. pseudintermedius was the sole organism in the remaining five pustules in case #2. Whole genome sequences revealed that all isolates tested were annotated as S. coagulans. The isolates from the same pustules exhibited identical genotypic and phenotypic profiles, indicating clonal multiplication. S. coagulans isolated from different pustules exhibited similar yet distinct genotypic and phenotypic profiles.<br> Conclusions S. coagulans with identical genetic and phenotypic profiles can be identified as the sole pathogen or coexist with S. pseudintermedius in the pustules of the same dogs with SBF. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1999-4923 18 1 2026 Streamlined Radiosynthesis of [18F]Fluproxadine (AF78): An Unprotected Guanidine Precursor Enables Efficient One-Step, Automation-Ready Labeling for Clinical Use 123 EN Xinyu Chen Nuclear Medicine, Faculty of Medicine, University of Augsburg Kaito Ohta Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Kimura Agency for Health, Safety and Environment, Kyoto University Yusuke Yagi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takanori Sasaki Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoko Nose Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaru Akehi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiko Yamane Department of Molecular Imaging Research, Kobe City Medical Center General Hospital Rudolf A. Werner Department of Nuclear Medicine, LMU Hospital, and German Cancer Consortium (DKTK), Partner Site Munich, Ludwig-Maximilians-University of Munich Takahiro Higuchi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: [18F]Fluproxadine (formerly [18F]AF78) is a PET radiotracer targeting the norepinephrine transporter (NET) with potential applications in cardiac, neurological, and oncological imaging. Its guanidine moiety, while essential for NET binding, presents major radiosynthetic challenges due to high basicity and the harsh deprotection conditions required for protected precursors. Previous methods relied on multistep procedures, strong acids, and complex purification, limiting clinical translation. This study aimed to develop a practical one-step radiosynthesis suitable for routine and automated production. Methods: A direct SN2-type nucleophilic [18F]fluorination was performed using an unprotected guanidine precursor to eliminate deprotection steps. Reaction parameters, including the base system, solvent composition, precursor concentration, and temperature, were optimized under conventional and microwave heating. Radiochemical conversion (RCC) and operational robustness were evaluated, and purification strategies were assessed for automation compatibility. Results: Direct [18F]fluorination using the unprotected precursor reduced the total synthesis time to 60–70 min. Optimal conditions employed a tert-butanol/acetonitrile (4:1) solvent system with K2CO3/Kryptofix222, affording RCC up to 33% under conventional heating. Microwave irradiation further improved efficiency, achieving RCC of up to 64% within 1.5 min at 140 °C. The method showed broad tolerance to variations in the base molar ratio and precursor concentration and enabled isocratic HPLC purification. Conclusions: This one-step radiosynthesis overcomes longstanding challenges in [18F]fluproxadine production by eliminating harsh deprotection and enabling high-yield, automation-ready synthesis, thereby improving clinical feasibility. No potential conflict of interest relevant to this article was reported.

Institute of Electrical and Electronics Engineers (IEEE) Acta Medica Okayama 2169-3536 14 2026 FEM-Based Design and Characterization of a Millimeter-Scale Piezoelectric Resonance Force Sensor 17960 17970 EN Aoto Yamazaki Department of Mechanical Engineering, Toyohashi University of Technology Takuma Akiduki Department of Mechanical Engineering, Toyohashi University of Technology Atsuo Honna Riccoh Company Ltd. Michiteru Kitazaki Department of Computer Science and Engineering, Toyohashi University of Technology Tomoaki Mashimo Graduate School of Natural Science and Technology, Okayama University This paper presents a millimeter-scale piezoelectric effect-based force sensor that uses the change in its resonant frequency as the detection principle for high sensitivity and a wide measurement range. Such characteristics are suited for robot hand applications that not only detect small forces but also handle large payloads. We develop a methodology to estimate the relationship between applied force and resonant frequency shift by combining classical contact theory and finite element method (FEM) analysis. Although this relationship is non-linear, the designability of sensitivity and measurement range is demonstrated by the simulation. The simulation results based on the method are verified, showing good agreement with the experimental results. The static characteristics, including sensitivity, standard deviation, and resolution, are evaluated using prototype sensors with characteristic lengths ranging from 1 mm to 4 mm. The 4-mm model has a measurement range of 77 mN to 300 N, and the smallest model, which is one of the smallest force sensors suitable for practical implementation, has a measurement range of 9 mN to 20 N. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1757-2215 19 1 2025 Pan-cancer profiling links C1orf50 to DNA repair and immune modulation in ovarian cancer 13 EN Anna Rogachevskaya Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School Yusuke Otani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Akira Ohtsu Harvard Medical School Vanessa D. Chin UMass Chan Medical School, UMass Memorial Medical Center Tirso Peña Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School Seiji Arai Department of Urology, Gunma University Graduate School of Medicine Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Atsushi Fujimura Department of Molecular Physiology, Faculty of Medicine, Graduate School of Medicine, Kagawa University Atsushi Tanaka Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School Background C1orf50 encodes a small, evolutionarily conserved protein, the function of which remains unclear. Its significance across various human cancers, particularly its specific role in ovarian cancer within an immunogenomic context, is not yet fully understood. Utilizing The Cancer Genome Atlas and single-cell RNA sequencing (scRNA-seq) public datasets, we conducted a comprehensive profiling of C1orf50 across multiple cancer types, with a particular focus on ovarian cancer, to investigate its associations with copy-number status, genomic instability, tumor programs, and the immune microenvironment.<br> Results Across cancer types, copy-number gain or amplification of C1orf50 was most frequent in ovarian cancer and closely tracked with higher messenger RNA levels. Higher C1orf50 expression was associated with a greater tumor mutational burden and homologous recombination deficiency, as indicated by gene-set patterns that suggested heightened cell-cycle and cellular stress responses accompanied by reduced oxidative phosphorylation, enrichment of regulatory T cells, and depletion of resting memory CD4 T cells. In ovarian cancer, focal events at chromosome 1p34.2 were accompanied by stepwise increases in C1orf50 expression by clinical stage and were linked to higher tumor mutational burden, homologous recombination deficiency, and greater loss of heterozygosity, together with more frequent gene alterations in BRCA1 or BRCA2. Immune composition clustered into profiles consistent with an immunosuppressive context in tumors with higher C1orf50 expression. The scRNA-seq data further revealed that cancer cells enhanced immune-suppressive interactions with various immune cell populations and diminished antigen-presentation signals. Analyses of genomic instability in ovarian cancer suggested mutational processes compatible with base-substitution patterns associated with cytidine deaminase activity and with insertion-deletion patterns characteristic of homologous recombination failure, while transcript-level patterns pointed to a broad downshift of canonical DNA repair activity with apparent compensatory adjustments in related pathways rather than a uniform change in any single pathway.<br> Conclusions The overexpression of C1orf50 characterizes an aggressive immunogenomic phenotype in ovarian cancer, distinguished by genomic instability, impaired DNA repair mechanisms, and extensive immunosuppression. These findings indicate that C1orf50 warrants consideration as a potential biomarker and a prospective target for therapeutic investigation. Furthermore, they advocate for the progression to prospective validation and functional studies to ascertain its clinical significance. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 1880-6546 76 1 2026 Effects of systemic ventricular assist combined with fenestration in failing Fontan: A theoretical analysis 100065 EN Shuji Shimizu Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Yasuhiro Kotani Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Naohiro Horio Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Eiri Kisamori Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Yoshinori Miyahara Pediatric Heart Disease and Adult Congenital Heart Disease Center, Showa Medical University Hospital Koji Uemura Department of Research Promotion and Management, National Cerebral and Cardiovascular Center Toshiaki Shishido Department of Research Promotion and Management, National Cerebral and Cardiovascular Center Shingo Kasahara Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Biventricular assist for failing Fontan circulation remains challenging. Because fenestration effectively reduces stressed blood volume and central venous pressure in Fontan patients with increased pulmonary vascular resistance (PVR), systemic ventricular assist device (VAD) combined with fenestration may improve hemodynamics in failing Fontan patients with increased PVR who would require biventricular assist. To validate this hypothesis, we performed a computational hemodynamic simulation of the failing Fontan circulation using a lumped parameter model. We compared hemodynamic variables between the models with and without fenestration while the PVR index was increased sequentially from 3.01 to 6.81 Wood Units m2. Following VAD initiation and stressed blood volume reduction, central venous pressure was maintained at a lower level in the fenestration models. This positive effect was greater in the model with larger fenestration diameter. However, excessive fenestration caused significant desaturation. In failing Fontan circulation with elevated PVR, systemic VAD combined with fenestration significantly improved hemodynamics. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2589-0042 28 9 2025 Extensive urine production in euryhaline red stingray for adaptation to hypoosmotic environments 113274 EN Naotaka Aburatani Atmosphere and Ocean Research Institute, The University of Tokyo Wataru Takagi Atmosphere and Ocean Research Institute, The University of Tokyo Marty Kwok-Shing Wong Atmosphere and Ocean Research Institute, The University of Tokyo Nobuhiro Ogawa Atmosphere and Ocean Research Institute, The University of Tokyo Shigehiro Kuraku Department of Genomics and Evolutionary Biology, National Institute of Genetics Mana Sato Department of Genomics and Evolutionary Biology, National Institute of Genetics Kazuhiro Saito Ushimado Marine Institute, Faculty of Science, Okayama University Waichiro Godo Ushimado Marine Institute, Faculty of Science, Okayama University Tatsuya Sakamoto Ushimado Marine Institute, Faculty of Science, Okayama University Susumu Hyodo Atmosphere and Ocean Research Institute, The University of Tokyo Maintaining water balance is a prerequisite for all organisms. Euryhaline elasmobranchs face the severest water-influx potential in fresh water (FW), as they retain high concentrations of urea even in hypotonic environments. To elucidate how they overcome this osmotic challenge, we assessed urine output in conscious euryhaline red stingrays (Hemitrygon akajei). Following acclimation to 5% diluted seawater, the stingrays increased urinary output by 87-fold―the greatest change observed in vertebrates―partly due to 6.8-fold increase in glomerular filtration rate (GFR). In the nephron, expressions of Aquaporin-1 (Aqp1), Aqp3, and Aqp15 were strongly downregulated in FW, indicating that tubular diuresis bridges the gap between GFR and final urine volume. Meanwhile, FW-acclimation upregulated Aqp1 and Aqp4 in the distinct bundle structure, which promotes urea reabsorption. Euryhaline elasmobranchs resolve the huge osmotic challenge of FW by excreting massive amounts of water and retaining osmolytes including urea through coordinated regulation of GFR and Aqp expressions. No potential conflict of interest relevant to this article was reported.

岡山大学大学院法務研究科 Acta Medica Okayama 1881-1485 27 2026 成年後見制度　〜中核機関の現状と課題〜 1 51 EN Kazuhiro NISHIDA Mika NISHIYAMA Okayama City Adult Gurdianship Center Case Ayaka NAGASHIO Okayama City Adult Gurdianship Center Case Kyosuke YOSHIOKA Soja City Case Tomono IMAI Chita Area Avocacy Center Case Yuji MIZUTA Oda City Case Daisuke UCHIDA Oda City Case 10.18926/OLR/70154 No potential conflict of interest relevant to this article was reported.

岡山大学大学院法務研究科 Acta Medica Okayama 1881-1485 27 2026 表紙・目次 EN No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1435-2451 410 1 2025 Robotic distal pancreatectomy using two-surgeon technique (TAKUMI-4): a technical note and initial outcomes 171 EN Kosei Takagi 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 Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Purpose With the increasing use of minimally invasive distal pancreatectomy, the use of robotic distal pancreatectomy (RDP) is also increasing worldwide. Standardized surgical protocols are essential for safe implementation of RDP. In this study, we present our surgical protocol and initial outcomes of RDP using “two-surgeon technique”.<br> Methods Our standard RDP protocol included a two-surgeon technique for cooperation, rationality, and education. Short-term outcomes of RDP were also investigated. This retrospective study included 77 consecutive patients who underwent RDP at our institution between April 2021 and January 2025.<br> Results The median operative time, estimated blood loss, and postoperative hospital stay were 214 min (interquartile range [IQR], 176–253), 10 mL (IQR, 0–50), and 9 days (IQR, 8–10), respectively. A textbook outcome was achieved in 84.4% of patients. Moreover, superior outcomes of RDP (n = 77) compared with those of laparoscopic distal pancreatectomy (n = 62) were confirmed in this study.<br> Conclusion Using the two-surgeon technique, we successfully standardized and introduced the RDP program. The two-surgeon technique can contribute to the safe introduction of RDP and expansion of the program. 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.

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

Springer Science and Business Media LLC Acta Medica Okayama 1865-7257 18 2 2025 Microsatellite-high intrahepatic cholangiocarcinoma with favorable treatment outcome using pembrolizumab 363 368 EN Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Hospital Kosaku Morimoto Department of Gastroenterology and Hepatology, Okayama University Hospital Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Hiroyuki Terasawa Department of Gastroenterology and Hepatology, Okayama University Hospital Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Takehiro Tanaka Department of Pathology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Intrahepatic cholangiocarcinoma has a poor prognosis. In unresectable cases, the survival period is short despite combination therapy with cytotoxic anticancer agents and immune checkpoint inhibitors. The usefulness of immune checkpoint inhibitors against malignant tumors with microsatellite instability-high (MSI-H) mutations was shown in the KEYNOTE158 study; however, data for intrahepatic cholangiocarcinoma are insufficient. In the present case, a 65-year-old man with intrahepatic cholangiocarcinoma and lymph node metastasis could not be treated with a combination of gemcitabine, CDDP, and S-1. A comprehensive cancer genomic profiling (CGP) test showed MLH1 pathogenic mutation and MSI-H. When pembrolizumab was administered, the tumor shrinkage effect was rapidly observed, which was sustained even after 30 months. No pathogenic mutations were observed in the germline test, and MSI-high was considered to be due to the MLH1 pathogenic mutation occurring sporadically in somatic cells. MSI-H intrahepatic cholangiocarcinoma is extremely rare. However, because pembrolizumab is expected to be effective, CGP testing should be actively performed. No potential conflict of interest relevant to this article was reported.

IOP Publishing Acta Medica Okayama 1742-6588 3027 1 2025 LES analysis to investigate a random-phase forcing scheme for steadying anisotropic turbulence fields 012009 EN Koki Minami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroki Suzuki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Toshinori Kouchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kento Tanaka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The aim of this study is to investigate the effect of phase randomization on forcing mechanisms that stabilize localized turbulence. A trigonometric forcing based on vector potential is combined with uniform random numbers to create a spatially homogeneous forcing field. The analysis is performed using large-eddy simulation (LES) with the Smagorinsky model as the subgrid scale model. The results demonstrate that steady flows are generated regardless of the presence of phase randomization, successfully forming isotropic turbulence. In contrast, for anisotropic turbulent fields, the addition of phase randomization reduces the degree of anisotropy, indicating a smoothing effect on the anisotropy of the flow. No potential conflict of interest relevant to this article was reported.

IOP Publishing Acta Medica Okayama 1742-6588 3027 1 2025 Fundamental examination of coherent structure model prediction using vortex cores in a two-dimensional Taylor’s analytical solution 012008 EN Xuanyou Gong Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroki Suzuki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Toshinori Kouchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kento Tanaka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University This study focuses on the possibility that flow around vortex tubes in turbulence may resemble laminar flow, and aims to describe the characteristics of turbulent fields using analytical solutions to the governing equations. In the two-dimensional analytical Taylor solution, the velocity and pressure fields are expressed by trigonometric functions, and a structure in which counter-rotating vortices are arranged in a grid pattern is demonstrated. This solution is used to verify the accuracy of numerical analyses and is expected to contribute to a simple yet unambiguous description of turbulent fields based on vortex structures. Predictions of sub-grid scale components and validation of a coherent structure model using invariants of the velocity gradient tensor are also performed. No potential conflict of interest relevant to this article was reported.

岡山大学農学部 Acta Medica Okayama 2186-7755 115 2026 Evaluation of Branching Characteristics and Their Contribution to Yield in Everbearing Strawberry Cultivars under Forced Cultivation 1 8 EN Minori Hikawa-Endo Kyushu Okinawa Region Agricultural Research Center, NARO Kazuyoshi Sone Kyushu Okinawa Region Agricultural Research Center, NARO Masami Morishita Kyushu Okinawa Region Agricultural Research Center, NARO 　Enhancing continuous flowering in cultivated strawberries may result in insufficient photosynthetic products due to the lower limit of leaf number on each lateral shoot, leading to reduced yield and fruit quality. If strawberries could differentiate an appropriate number of tillers and allow each tiller to grow autonomously with sufficient leaf number on each lateral shoot, rather than flowering continuously on the main bud alone, plants could achieve high yields while preventing plant weakening and fruit quality deterioration. Therefore, this study evaluated branching characteristics of everbearing strawberry cultivars under forcing cultivation to identify cultivars with moderate tillering and moderately low continuous flowering. Pot experiments revealed that the number of tillers was high in ‘Summer Princess’ and ‘Miyazaki-natsuharuka’ but low in ‘Summer Berry’ and ‘Suzuakane’. This trend was independent of total number of lateral shoots, nodal position of first inflorescence, and the number of leaves on each lateral shoot, which serve as indicators of continuous flowering ability. Among seven tested cultivars, ‘DT17’ and ‘Miyazaki-natsuharuka’ showed intermediate values with 2.1 - 2.5 tillers per plant and 6.7 - 7.7 leaves on each lateral shoots. These cultivars showed yields of 747.0 - 1,028.5 g per plant under forcing cultivation, which were higher than other cultivars, along with consistent fruit quality. These results suggest that improving branching characteristics is a practical approach to enhancing fruit productivity in strawberries. No potential conflict of interest relevant to this article was reported.

岡山大学農学部 Acta Medica Okayama 2186-7755 115 2026 表紙 EN No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構 Acta Medica Okayama 1881-5952 3 2026 近代韓国の読本教科書『初等小学』の底本に関する再考 74 90 EN Ankoo LEE Institute for Promotion of Education and Campus Life, Okayama University 10.18926/70113 　本稿では、近代韓国の読本教科書『初等小学』（1906）の編纂において参照されたと思われる日本の明治期読本教科書について比較・考察を行った。まず、文部省編纂の検定『尋常小学読本』（1887）と第1期国定『尋常小学読本』（1903）、さらに金港堂出版の『尋常国語読本』（1900）及び『高等国語読本』（1900）との関連性について、先行研究の議論を再検討した。そのうえで、新たに金港堂の『新体読本 尋常小学用』（1894）と普及舎の『尋常小学新読本』（1893）の2種を底本として確認することができた。『初等小学』において最も多く参照された明治期読本教科書は金港堂の『尋常国語読本』（1900）であり、『初等小学』は、金港堂と文部省の比較的新しい尋常小学用読本教科書を優先的に参照したと思われる。 No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構 Acta Medica Okayama 1881-5952 3 2026 オンラインによるボランティア日本語教室における参加者間のインターアクションの分析 ―地域型日本語教育の実現に向けて― 31 40 EN Miwa SUESHIGE Institute for Promotion of Education and Campus Life, Okayama University 10.18926/70110 本研究では，地域型日本語教育のモデル構築に向け，地域型の特徴を有する教室内での支援者および参加者の発話や教授行動の傾向を明らかにすべく，外国語相互作用分析システムを用い，オンラインによるボランティア教室におけるインターアクションの分析を行った。分析の結果，（1）支援者の平均発話数が学習者より多いこと，（2）支援者の発話における間接的行動の割合が直接的行動よりもやや高いことが示された。「おしゃべり型の教育」では，学習者が伝えたいことを言語化していくプロセスの中で，間接的行動の下位分類の「質問」「学習者の意図の利用」「学習者の回答の繰り返し」等を支援者が積極的に使用し支援していることが分かった。 No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構 Acta Medica Okayama 1881-5952 3 2026 心理臨床家同士のグループ体験における反省的実践 12 30 EN Ryosuke KOBASHI Institute for Promotion of Education and Campus Life, Okayama University Masashi TANAKA Tokai University Rin MURASE Graduate School of Education and Human Development, Nagoya University 10.18926/70109 　心理臨床家にとって反省的実践は重要であり，多様な形態のグループに参加をすることによって反省的実践を行っている。本研究では，全般的な心理臨床家同士のグループにおける体験（研究1）および継続的なグループにおける体験（研究2）を探索することを目的として，数名の心理臨床家による話し合いをKJ法を援用して分析した。その結果，心理臨床家同士のグループ体験における反省的実践には，【グループ体験が内省につながるかどうか】などの4つ側面が重要であることが示された。また，継続的なグループにおける体験では，《本来の人としての感覚や欲求》や《自分を不自由にしている要因》などの【会における気づき】が得られることが反省的実践として有意義であることが明らかになった。 No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構 Acta Medica Okayama 1881-5952 3 2026 セクシュアリティのゆらぎと発達障害のADHDとの関連 1 11 EN Megumi MATSUI Institute for Promotion of Education and Campus Life, Okayama University 10.18926/70108 　セクシュアリティのゆらぎと発達障害のADHDとの関連を明らかにするため，WEBによる縦断調査を行った。18歳以上の成人を対象とし，第1回目の調査は11,018人，1年後の第2回目の調査では5,474人から回答を得た。性自認，性的指向，性表現の様々なセクシュアリティについて，2回の調査での該当・非該当で4群に分け，ADHD得点について1要因の被験者間分散分析を行った。「デミロマンティック」「デミセクシュアル」以外で群の主効果が有意であり，「異性愛」「ゲイ」を除くセクシュアリティで，2回とも「非該当」群よりも「該当→非該当」群のADHD得点が有意に高かった。これによりセクシュアリティのゆらぎとADHDとの関連が示唆された。 No potential conflict of interest relevant to this article was reported.

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

岡山大学教育推進機構 Acta Medica Okayama 1881-5952 3 2026 表紙・目次 EN No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1865-1380 19 1 2026 Association of Wet-Bulb Globe Temperature with heat-related illness hospitalizations in Japan: a time-stratified, case-crossover study 11 EN Yuka Yamamura Department of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Fumiya Sasai Department of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Kohei Tokioka Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Jun Kanda Emergency and Critical Care Medicine, Nippon Medical School Musashikosugi Hospital Shoji Yokobori Department of Emergency and Critical Care Medicine, Nippon Medical School Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Takashi Yorifuji Department of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Background Heat-related illnesses are a serious public health concern and are exacerbated by global warming. Wet-Bulb Globe Temperature (WBGT) is widely used as a heat stress indicator, but its clinical impact remains unclear. This study aimed to investigate the association between hourly variations in WBGT and the incidence of hospitalizations for heat-related illness in Japan using a nationwide database. By incorporating individual-level clinical data and performing stratified analyses, we sought to provide a more granular understanding of how heat exposure affects the risk of heat-related illness requiring hospitalization.<br> Methods We conducted a time-stratified, case-crossover study using data collected from July to September in 2020 and 2021 in the Heatstroke STUDY registry. The inclusion criteria were patients registered in the Heatstroke STUDY registry, specifically hospitalized patients with heat-related illness who were transported to participating hospitals during the study period. Hourly WBGT values were assigned based on the nearest monitoring station to each hospital. Conditional logistic regression and distributed lag models were used to estimate associations between WBGT and the risk of hospitalization.<br> Results A total of 1,653 heat-related illness hospitalizations were analyzed. The mean patient age was 67.9 years; 67.6% were male. Each 1 °C increase in WBGT at onset (hospital arrival) was associated with a significantly increased risk of hospitalization (OR 1.10, 95% CI: 1.05–1.15). The cumulative effect over the prior six hours was also significant (OR 1.56, 95% CI: 1.50–1.62). Compared with WBGT < 25 °C, adjusted ORs were 3.39 (25–27 °C), 8.81 (28–30 °C), and 22.10 (≥ 31 °C). Stratified analyses suggested stronger associations among several subgroups; however, only patients with mental disorders showed statistically significant effect modification, whereas elevated WBGT posed a risk across all groups.<br> Conclusions Higher WBGT levels were associated with an increased risk of heat-related hospitalization. Although the effect appeared greater in some subgroups, only patients with mental disorders demonstrated statistically significant effect modification, suggesting elevated WBGT confers risk broadly. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 11 2025 Association of Carboxyhemoglobin With Severity and Outcomes in Hypothermic Patients: A Retrospective Cohort Study e97962 EN Yuya Miyoshi 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 Takashi Hongo 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 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 Introduction<br> Carboxyhemoglobin (COHb), an endogenous marker of carbon monoxide production mediated by heme oxygenase-1, may reflect physiological stress responses in critically ill patients. However, its clinical relevance in accidental hypothermia remains unclear.<br> <br> Methods<br> We conducted a single-center retrospective cohort study of adult patients admitted to the emergency ICU with accidental hypothermia between January 1, 2019, and March 31, 2025. Patients were categorized into low- and high-COHb groups based on median COHb levels upon emergency department arrival. Associations between COHb levels, disease severity (Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores), and 28-day mortality were analyzed using regression models adjusted for clinical confounders.<br> <br> Results<br> Among the 88 patients, who had a median admission temperature of 28.7°C, 45 were classified into the low-COHb group and 43 into the high-COHb group, based on a median COHb level of 0.3%. Lower COHb levels on admission were significantly associated with higher APACHE II scores (β = −4.20; 95% CI, −7.56 to −0.85), but not with SOFA scores. Admission and minimum COHb levels were not associated with 28-day mortality. However, higher maximum COHb levels within the first 24 hours were independently associated with lower 28-day mortality (adjusted OR, 0.17; 95% CI, 0.023 to 0.93).<br> <br> Conclusions<br> Lower COHb levels were associated with greater disease severity, and higher maximum COHb levels were associated with lower 28-day mortality. COHb may reflect systemic stress in accidental hypothermia, but its prognostic value appears limited. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 18 4 2026 Antigen Remodeling in Colorectal Cancer: How Radiotherapy and Chemotherapy Enhance Immunotherapy Responsiveness 715 EN 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 Toshiaki Takahashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Moriwake Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masashi Kayano Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Colorectal cancer (CRC) is traditionally considered a “cold tumor” characterized by low immunogenicity and limited responsiveness to immune checkpoint inhibitors (ICIs). However, recent findings reveal that cytotoxic modalities can reprogram this immunologically inert landscape. This review integrates these evolving concepts to guide the optimization of future treatments. Radiotherapy induces extensive DNA double-strand breaks, which may generate de novo mutations through error-prone repair while simultaneously exposing cryptic antigens via increased transcriptional instability, alternative splicing, and enhanced proteasomal processing. Chemoradiation also amplifies epigenetic and epitranscriptomic sources of neoepitope diversity, including RNA editing and stress-induced splicing alterations, expanding the immunopeptidome beyond canonical mutation-driven neoantigens. These changes collectively enhance antigen presentation and facilitate T-cell priming. Chemotherapy further reduces immunosuppressive cell populations and promotes dendritic cell activation, creating a permissive milieu for subsequent immune engagement. Clinically, the VOLTAGE studies demonstrated that long-course chemoradiotherapy can sensitize even mismatch repair–proficient rectal cancers to PD-1 blockade, yielding clinically meaningful pathological responses. In contrast, mismatch repair–deficient rectal tumors may respond completely to ICIs alone. Short-course radiotherapy combined with chemotherapy and ICIs has also shown encouraging activity in the setting of total neoadjuvant therapy. Collectively, these findings support a paradigm in which radiotherapy, chemotherapy, and epigenetic/epitranscriptomic alterations―including RNA editing―act as potent modulators of tumor antigenicity. By expanding the neoantigen repertoire and reshaping the tumor microenvironment, these strategies can transform CRC from a cold tumor into one that is increasingly responsive to immunotherapy. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2730-664X 6 1 2026 Effects of an oral exercise intervention on pre-frailty or frailty in older people: a randomized clinical trial 96 EN Noriko Takeuchi Department of Preventive Dentistry, Division of Dentistry, Medical Development Field, Okayama University Nanami Sawada Section of Preventive and Public Health Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University Sakura Inada Division of Health Promotion, Okayama-City Health Center Manabu Morita Department of Oral Health Sciences, Faculty of Health Care Sciences, Takarazuka University of Medical and Health Care Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Frailty is often experienced by older adults, which can lead to long-term health problems. We aimed to examine associations with improvements in nutritional status, sarcopenia (age-related loss of skeletal muscle mass and strength), and frailty in four groups with different oral exercise frequencies.<br> Methods: We conducted a prospective, parallel multi-arm randomized controlled trial (Japan Registry of Clinical Trials (jRCT) 1062210063) to test the effects of oral exercise on frailty in older adults. Each intervention consisted of a standardized oral exercise protocol including neck exercises, lip exercises, and tongue movements, designed to improve oral function and reduce frailty. The primary outcome was the change in the number of frailty criteria from baseline to follow-up. Individuals aged ≥60 years were screened for frailty status using standardized criteria at the Department of Preventive Dentistry at Okayama University Hospital between October 2022 and December 2023. Those identified as pre-frailty or frailty were eligible and enrolled in the study. After screening 60 individuals, 58 eligible participants were randomly assigned using block randomization to one of four oral exercise frequency groups: 3 times/day & everyday, 3 times/day & 3 days/week, once/day & everyday, and once/day & 3 days/week. A two-way repeated measures analysis of variance was used to evaluate the impact of the four frequencies of oral exercise methods on frailty in older adults. Outcome assessors were blinded; participants were not.<br> Results: Here we show the results of the 58 participants. Group sizes are: 3 times/day & everyday (n = 14), 3 times/day & 3 days/week (n = 15), once/day & everyday (n = 14), once/day & 3 days/week (n = 15). The trial is completed as planned, and all randomized participants are analyzed. The main effect of time is significant for the number of frailty criteria (F = 14.803, p < 0.001, partial eta squared = 0.215). The mean changes from baseline to follow-up are −0.357 (95% Confidence Interval −0.787 to 0.073) in the 3 times/day & everyday group, −0.600 (95% Confidence Interval −1.255 to 0.055) in the 3 times/day & 3 days/week group, −0.571 (95% Confidence Interval −1.379 to 0.236) in the once/day & everyday group, and −0.600 (95% Confidence Interval −1.008 to −0.192) in the once/day & 3 days/week group. The main effect of time is also significant for the number of oral hypofunction criteria (F = 16.456, p < 0.001, partial eta squared = 0.234). No important adverse events or side effects related to the intervention were observed.<br> Conclusions: After conducting oral exercises for 3 months on older adults with pre-frailty or frailty, improvements in frailty are observed. Overall, these exercises could be a simple, low-cost way to support healthy aging in the community. No potential conflict of interest relevant to this article was reported.

Cambridge University Press (CUP) Acta Medica Okayama 1460-3969 25 2026 Effects of sagging correction calibration error on radiation therapy equipment using image analysis e5 EN Yasushi Fujii Department of Radiology, Chugoku Central Hospital of the Mutual Aid Association of Public School Teachers Takahiro Nakayama Department of Radiology, Chugoku Central Hospital of the Mutual Aid Association of Public School Teachers Junki Oshita Department of Radiology, Chugoku Central Hospital of the Mutual Aid Association of Public School Teachers Ayaka Tsunoda Department of Radiology, Graduate School of Health Sciences, Okayama University Yusuke Saeki Department of Radiological Technology, Kawasaki Medical School Hospital Yoshinori Tanabe Faculty of Medicine, Graduate School of Health Sciences, Okayama University Purpose: This study investigates the effect of sagging correction errors on image quality and geometric coordinate accuracy.<br> Methods: This study utilised the Elekta radiotherapy system, ball bearing (BB), Catphan phantom and MultiMet-WL phantom. Ten distinct flex maps (FMs) were acquired by positioning the BB at the accuracy isocentre and introducing shifts of 0.2, 0.4 and 0.6 mm in the left, table and up directions, respectively. Cone-beam computed tomography images of the Catphan phantom were acquired using 10 FMs. The images were analysed for modulation transfer function (MTF) values and geometric coordinates. Additionally, the Winston–Lutz (W-L) test was conducted under reference couch positions and with a 0.3 mm couch shift.<br> Results: For the Catphan phantom analysis, the standard deviations of MTF10% across FMs were 0.19. The centre-of-gravity coordinates of the insert exhibited shifts of approximately 0.2, 0.4 and 0.6 mm when comparing reference images to those acquired with the shifted FMs. The results of the W-L test with a 0.3 mm couch shift showed radiation isocentre deviations exceeding 1 mm compared to the reference couch positions.<br> Conclusions: Minor sagging correction calibration errors did not remarkably impact image quality; however, they altered the geometric coordinates of the image isocentre. These calibration errors decreased the accuracy of off-isocentre positioning. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 18 1 2026 Saliva as a Reliable and Non-invasive Sample for Detecting Influenza A in Severe Acute Respiratory Infection Cases e100872 EN Junko S Takeuchi Department of Academic-Industrial Partnerships Promotion, Center for Clinical Sciences, Japan Institute for Health Security Nobuaki Matsunaga Antimicrobial Resistance (AMR) Clinical Reference Center, Japan Institute for Health Security Ai Tsukada Antimicrobial Resistance (AMR) Clinical Reference Center, Japan Institute for Health Security Noriko Iwamoto Disease Control and Prevention Center, Japan Institute for Health Security Noriko Fuwa Disease Control and Prevention Center, Japan Institute for Health Security Takahiro Ichikawa Department of Infectious Diseases, Sapporo City General Hospital Yasuyuki Kato Department of Infectious Diseases, International University of Health and Welfare (IUHW) Narita Hospital Yuka Tomita Department of Infectious Diseases, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital Hiroki Kitagawa Department of Infectious Diseases, Hiroshima University Hospital Masaya Yamato Department of General Internal Medicine and Infectious Diseases, Rinku General Medical Center Tetsuji Aoyagi Department of Clinical Infectious Diseases, Tohoku University Graduate School of Medicine Hideharu Hagiya Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryota Hase Department of Infectious Diseases, Japanese Red Cross Narita Hospital Shuji Hatakeyama Division of Infectious Diseases, Jichi Medical University Hospital Tohru Inaba Department of Infection Control and Laboratory Medicine, Kyoto Prefectural University of Medicine Koichi Izumikawa Yoshio Takesue Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences Moto Kimura Department of Academic-Industrial Partnerships Promotion, Center for Clinical Sciences, Japan Institute for Health Security Norio Ohmagari Disease Control and Prevention Center, Japan Institute for Health Security Background<br> Nasopharyngeal swab sampling remains the gold standard for influenza diagnosis; however, it has several limitations, including dependence on medical staff, invasiveness, potential for nosocomial transmission, and occupational exposure risk. Non-invasive alternatives, such as saliva and nasal vestibular swabs, may improve patient comfort and participation in clinical studies. In addition, diagnosis with reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) is often delayed because it requires trained laboratory technicians and facilities with appropriate laboratory settings. Although rapid diagnostic devices such as the GenPad® offer potential alternatives to RT-qPCR, their performance with non-invasive samples remains insufficiently explored. This study addresses the two key questions for influenza detection in severe acute respiratory infection (SARI) cases: (i) whether saliva or nasal vestibular swab samples serve as suitable alternatives to nasopharyngeal swab samples, and (ii) whether the GenPad® provides a reliable option for detecting influenza using saliva samples.<br> Methodology<br> A prospective observational study was conducted with 16 inpatients classified as having SARIs and diagnosed with influenza between December 2024 and March 2025 in Japan. Paired saliva and nasal vestibular swab samples were collected 1-9 (median = 3.5) days after symptom onset. RT-qPCR testing was performed according to the National Institute of Infectious Diseases protocol. Saliva samples were also tested using the GenPad® system. Comparisons between sample types and diagnostic methods were analyzed using the exact McNemar's test.<br> Results<br> Among the 16 influenza-positive patients, saliva samples demonstrated higher sensitivity (87.5%) than nasal vestibular swabs (31.3%) in RT-qPCR when compared with the diagnostic results obtained from nasopharyngeal swabs. A comparison of RT-qPCR results between saliva and nasal vestibular swabs revealed a total agreement of 43.8%, with exact McNemar's test showing a significant difference (p = 0.0039). While nasal vestibular swabs showed inconsistent results, saliva samples consistently tested positive, particularly within seven days of symptom onset (100% positive agreement). The GenPad®, a rapid diagnostic device, showed promising performance (92.9%) using saliva samples compared to RT-qPCR.<br> Conclusions<br> Saliva is a reliable non-invasive alternative to nasopharyngeal swabs for influenza detection in SARI cases, particularly within seven days of symptom onset, whereas nasal vestibular swabs show lower sensitivity. Additionally, the GenPad® provides comparable performance to RT-qPCR using saliva samples, offering a rapid, portable diagnostic option. These approaches may mitigate discomfort, minimize infection risk for healthcare workers, and improve testing capacity. However, the absence of influenza-negative controls and the small sample size (n = 16) substantially limit the assessment of diagnostic accuracy and specificity. As a result, the broader applicability of our findings should be interpreted with caution, and further studies are required to validate these observations. 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.<br> 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.<br> 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.<br> 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.

MDPI AG Acta Medica Okayama 2078-2489 17 1 2026 An SQL Query Description Problem with AI Assistance for an SQL Programming Learning Assistant System 65 EN Ni Wayan Wardani Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Htoo Htoo Sandi Kyaw Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Zihao Zhu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University I Nyoman Darma Kotama Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Putu Sugiartawan Graduate School of Environmental, Life, Natural Science and Technology, Okayama University I Nyoman Agus Suarya Putra Faculty of Business and Creative Design, Indonesian Institute of Business and Technology Today, relational databases are widely used in information systems. SQL (structured query language) is taught extensively in universities and professional schools across the globe as a programming language for its data management and accesses. Previously, we have studied a web-based programming learning assistant system (PLAS) to help novice students learn popular programming languages by themselves through solving various types of exercises. For SQL programming, we have implemented the grammar-concept understanding problem (GUP) and the comment insertion problem (CIP) for its initial studies. In this paper, we propose an SQL Query Description Problem (SDP) as a new exercise type for describing the SQL query to a specified request in a MySQL database system. To reduce teachers’ preparation workloads, we integrate a generative AI-assisted SQL query generator to automatically generate a new SDP instance with a given dataset. An SDP instance consists of a table, a set of questions and corresponding queries. Answer correctness is determined by enhanced string matching against an answer module that includes multiple semantically equivalent canonical queries. For evaluation, we generated 11 SDP instances on basic topics using the generator, where we found that Gemini 3.0 Pro exhibited higher pedagogical consistency compared to ChatGPT-5.0, achieving perfect scores in Sensibleness, Topicality, and Readiness metrics. Then, we assigned the generated instances to 32 undergraduate students at the Indonesian Institute of Business and Technology (INSTIKI). The results showed an average correct answer rate of 95.2% and a mean SUS score of 78, which demonstrates strong initial student performance and system acceptance. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2813-2203 5 1 2025 A Threshold Selection Method in Code Plagiarism Checking Function for Code Writing Problem in Java Programming Learning Assistant System Considering AI-Generated Codes 2 EN Perwira Annissa Dyah Permatasari Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mustika Mentari Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Safira Adine Kinari Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Soe Thandar Aung Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Htoo Htoo Sandi Kyaw Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Khaing Hsu Wai Graduate School of Engineering Science, Akita University To support novice learners, the Java programming learning assistant system (JPLAS) has been developed with various features. Among them, code writing problem (CWP) assigns writing an answer code that passes a given test code. The correctness of an answer code is validated by running it on JUnit. In previous works, we implemented a code plagiarism checking function that calculates the similarity score for each pair of answer codes based on the Levenshtein distance. When the score is higher than a given threshold, this pair is regarded as plagiarism. However, a method for finding the proper threshold has not been studied. In addition, AI-generated codes have become threats in plagiarism, as AI has grown in popularity, which should be investigated. In this paper, we propose a threshold selection method based on Tukey’s IQR fences. It uses a custom upper threshold derived from the statistical distribution of similarity scores for each assignment. To better accommodate skewed similarity distributions, the method introduces a simple percentile-based adjustment for determining the upper threshold. We also design prompts to generate answer codes using generative AI and apply them to four AI models. For evaluation, we used a total of 745 source codes of two datasets. The first dataset consists of 420 answer codes across 12 CWP instances from 35 first-year undergraduate students in the State Polytechnic of Malang, Indonesia (POLINEMA). The second dataset includes 325 answer codes across five CWP assignments from 65 third-year undergraduate students at Okayama University, Japan. The applications of our proposals found the following: (1) any pair of student codes whose score is higher than the selected threshold has some evidence of plagiarism, (2) some student codes have a higher similarity than the threshold with AI-generated codes, indicating the use of generative AI, and (3) multiple AI models can generate code that resembles student-written code, despite adopting different implementations. The validity of our proposal is confirmed. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Metastatic Intraocular Tumor Likely from Hepatocellular Carcinoma Mimicking Panuveitis 63 67 EN Eri Takasu Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Shiode Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroya Kindo Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Kimura Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mio Hosokawa Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Kanzaki Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuro Morita Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Adachi 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 Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/70074 A 77-year-old man undergoing treatment for hepatocellular carcinoma (HCC) presented with blurred vision in his right eye, persisting for 2 months. Slit-lamp microscopy and fundus examination revealed inflammatory cells in the anterior chamber, severe vitreous opacities, and retinal vasculitis in the right eye. The patient underwent vitreous surgery with biopsy, and vitreous cytology confirmed a metastatic intraocular tumor originating from the HCC. Radiotherapy was administered to the right eye, with no recurrence of intraocular inflammation observed at 10 months post-irradiation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Changes in Prescribing Patterns of Antiviral Drugs before and after Public Coverage Termination among Hospitalized COVID-19 Patients in Regional Hospitals in Japan: A Retrospective, Multicenter Study 55 62 EN Hidemasa Akazawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Shohei Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Yasuhiro Nakano 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, Original Article 10.18926/AMO/70073 In Japan, antiviral agents for COVID-19 were freely available until September 2023 as part of national policy. This study evaluated changes in these agents’ prescribing patterns and the patient outcomes following the policy shift. We conducted a multicenter retrospective study at four hospitals in Japan’s Okayama and Kagawa prefectures from January 2022 to March 2024. The study period was divided into the public-expenditure phase (January 2022 to September 2023) and the post-expenditure phase (October 2023 to March 2024). We extracted the hospitalized patients’ clinical data from the electronic database. The study’s primary outcome was the antiviral prescription rate; the secondary outcome was in-hospital mortality. Among the 302 hospitalized patients (median age 85 years), 52.0% were classified as having a mild condition. Of the patients with mild conditions, 37.7% were diagnosed in outpatient settings prior to hospitalization. During the public-expenditure phase, 47.4% of the patients received antivirals as outpatients, mainly molnupiravir (80.9%). In the post-expenditure period, 80.0% of the patients were prescribed antivirals, mostly molnupiravir (91.7%). The antiviral prescription rate was significantly higher after the policy change. The overall in-hospital mortality was 15.8%, with no significant difference between the two periods (17.0% vs. 10.5%). Despite the termination of government funding, antiviral prescriptions remained frequent at community hospitals located in highly aging regions of western Japan such as Okayama and Kagawa prefectures. Mortality remains high among the elderly, highlighting the need for continued antiviral therapy and booster vaccinations. 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.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Kinesiophobia Is Associated with Disability, Poor Quality of Life, Psychological Morbidity, and Surgery Dissatisfaction in Patients with Lumbar Microdiscetomy: A Cross-Sectional Controlled Study 39 46 EN Nihal Tezel Department of Physical and Rehabilitation Medicine, Health Sciences University Aslı Gençay Can Department of Physical and Rehabilitation Medicine, Faculty of Medicine, Ankara Yıldırım Beyazıt University Original Article 10.18926/AMO/70071 The study aimed to determine the prevalence of kinesiophobia in patients who had undergone lumbar microdiscectomy and to examine its associations with pain intensity, disability, quality of life, depression, anxiety, and satisfaction with surgery. Forty-eight patients with microdiscectomy and 48 healthy controls were enrolled. The Tampa Scale for Kinesiophobia (TSK), Roland-Morris Disability Index (RMDI), Hospital Anxiety and Depression Scale (HADS-A and HADS-D, respectively), and Short Form-36 Health Survey (SF-36) were administered to both groups. The scores of TSK, RMDI, HADS-A, and HADS-D were significantly higher and SF-36 scores were significantly lower in the microdiscectomy than the control group (p<0.001 for all). In the microdiscectomy group, median (min-max) RMDI, HADS-A, and HADS-D scores were 19 (4-34), 10 (0-18), and 9 (0-18), respectively, in kinesiophobic patients, and were significantly higher than 6 (2-20), 3 (0-11), 2.5 (0-11) in non-kinesiophobic patients (all p<0.001). The median (min-max) SF-36 PCS, SF-36 MCS, and VAS scores for surgery satisfaction were 36.5 (8.7-75), 52.1 (11-95), 5, 5 (0-10), respectively, in kinesiophobic patients and were significantly lower than 71 (28-95), 85.5 (9-93), 8.5 (3-10) in non-kinesiophobic patients (all p<0.05). TSK scores were significantly correlated with RMDI, HADS-A, HADS-D, SF-36, and surgery satisfaction scores (all p<0.05). Kinesiophobic patients with lumbar microdiscectomy therefore showed greater disability and psychological morbidity, poorer quality of life, and lower satisfaction with surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 The Preoperative Anterior Pelvic Plane Angle Predicts Cup Anteversion Changes at 1 Year after Total Hip Arthroplasty 31 37 EN Kyota Ishibashi Department of Orthopedic Surgery, Hachinohe City Hospital Hirotaka Oishi Department of Orthopedic Surgery, Hachinohe City Hospital Ryo Araki Department of Orthopedic Surgery, Hachinohe City Hospital Kosuke Kawamura Department of Orthopedic Surgery, Hachinohe City Hospital Isamu Sasaki Department of Orthopedic Surgery, Hachinohe City Hospital Eiji Sasaki Department of Orthopedic Surgery, Hirosaki University Graduate School of Medicine Hikaru Kamada Department of Orthopedic Surgery, Hachinohe City Hospital Masakazu Kogawa Department of Orthopedic Surgery, Hachinohe City Hospital Sunao Tanaka Department of Orthopedic Surgery, Hachinohe City Hospital Takuya Numasawa Department of Orthopedic Surgery, Hachinohe City Hospital Yasuyuki Ishibashi Department of Orthopedic Surgery, Hirosaki University Graduate School of Medicine Original Article 10.18926/AMO/70070 We investigated global alignment changes following total hip arthroplasty (THA) and predictive alignment parameters for increased cup anteversion (CA) by retrospectively analyzing the primary THA data of 75 patients treated at our hospital (49 women, 26 men; age 65.1±5.7 years, BMI 28.3±3.4 kg/m2). Global alignment parameters, i.e., the anterior pelvic plane angle (APPa) and proximal femoral shaft angle (PFSa) and other alignment parameters were measured. CA was evaluated based on the patients’ standing coronal radiographs. ΔCA was defined as the difference in CA from 2 weeks before to 1 year after each THA. We classified the cases as stable (S) (CA < 10°; n=63) and pelvic retroversion (R) (CA ≥ 10°; n=12) groups. Associations between ΔCA and alignment parameters were evaluated by linear regression and a receiver operating characteristic (ROC) analysis. A significant decrease in the PFSa occurred between the 2-week and 1-year post-THA timepoints (7.8±4.3° vs. 4.2±3.6°, p<0.001), with no notable change in other alignment parameters. At 1-year post-THA, the CA of 12 (16%) patients had increased to 4.5±4.4°. Only the preoperative APPa was positively associated with ΔCA (β=0.165, p=0.020). The ROC analysis revealed that the optimal cut-off value for increased CA in the APPa is 2.1° (area under the curve, 0.700; p=0.020; odds ratio, 4.80). The APPa change predicted increased CA, which emphasizes the importance of the use of preoperative standing radiography for identifying the optimal cup positioning for post-THA changes in CA. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Development of a Stroke Discharge Support Evaluation Scale for Ward Nurses in Acute Care Hospitals 17 30 EN Hideki Yano Department of Nursing, Faculty of Human Health Sciences, Niimi University Yoko Takahata Graduate School of Health Sciences, Okayama University Takeshi Yamaguchi Faculty of Nursing, Shikoku University Shinya Saito Graduate School of Health Sciences, Okayama University Original Article 10.18926/AMO/70069 This study aimed to develop a scale enabling nurses to objectively evaluate their own stroke discharge support, as a basis for enhancing its overall effectiveness. A draft scale was created based on a literature review, and consisted of a 51-item, 5-point Likert-type questionnaire administered to ward nurses engaged in stroke discharge support at acute care hospitals. Factor analysis was performed to refine the scale. Construct validity was assessed using the known-groups method, and reliability was evaluated through internal consistency analysis. The resulting Stroke Discharge Support Evaluation Scale comprises 29 items across 5 factors, each rated on a 5-point Likert scale. Analysis of the data collected from 237 valid responses demonstrated good internal consistency and supported the scale’s construct validity. The Stroke Discharge Support Evaluation Scale is a reliable and valid tool enabling ward nurses in acute care hospitals to evaluate their own stroke discharge support. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 A Novel Nomogram that Predicts Chronic Hemodialysis Patients’ Survival Based on Their Sedentary Behavior 9 16 EN Kentaro Sugahara Department of Hygiene, Faculty of Medicine, Kagawa University Takashi Kondo Innoshima General Hospital Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Hiroyuki Nishi Innoshima General Hospital Kazuhiro Ujike Innoshima General Hospital Kiichi Koumoto Innoshima General Hospital Keiichi Namio Department of Hygiene, Faculty of Medicine, Kagawa University Shuhei Hishii Department of Hygiene, Faculty of Medicine, Kagawa University Akihiko Katayama Faculty of Social Studies, Shikokugakuin University Hiromi Suzuki Department of Hygiene, Faculty of Medicine, Kagawa University Yorimasa Yamamoto Innoshima General Hospital Original Article 10.18926/AMO/70068 Appropriate treatments for chronic hemodialysis patients are a public health challenge in Japan. Sedentary behavior appears to be closely associated with these patients’ survival. We thus sought to develop a nomogram that predicts survival based on the duration of chronic hemodialysis patients’ sedentary behavior. One hundred twenty-four patients under chronic hemodialysis (73 men, 51 women, age 71.7±11.1 years) were enrolled in this cohort study. The patients wore a triaxial accelerometer that measured both their sedentary behavior, i.e., total sedentary behavior (minutes) and their maximum sedentary bouts (min) on non-hemodialysis days. We obtained the Kaplan-Meier curve and used the log-rank test and a Cox proportional hazards model to evaluate the relationship between the patients’ sedentary behavior and their survival. We also used a Cox proportional hazards model to develop a nomogram for the patients’ 5-year survival rate. Forty-six patients died during the follow-up period. When we stratified the patients by the medians of total sedentary behavior and maximum sedentary bouts, we observed significant between-group differences. After adjustment for confounding factors in a Cox proportional hazards model, total sedentary behavior and maximum sedentary bouts were identified as critical survival factors, and we generated a nomogram using an index of sedentary behavior. Our analysis results demonstrated that sedentary behavior on non-dialysis days was closely associated with the survival of the chronic hemodialysis patients, suggesting that a decrease in sedentary behavior would prolong their survival. The nomogram developed herein based on sedentary behavior may be useful for predicting the outcomes of chronic hemodialysis patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Usefulness of D-dimer Assay to Confirm the Course of Overt Venous Thromboembolism (VTE) in Cancer Patients 1 7 EN Hidenaru Yamaoka Department of Cardiovascular Medicine, IMS Tokyo Katsushika General Hospital Masashi Yoshida Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshihiro Sarashina Seisukai Kuroda Clinic Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuru Munemasa Department of Cardiovascular Medicine, Okayama Rosai Hospital Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ito Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/70067 Venous thromboembolism (VTE) is a serious complication in patients with cancer. In this population, the presence of thrombi is often assessed at cancer diagnosis by measuring D-dimer levels, which have high sensitivity but low specificity for identifying VTE at this clinical time point. However, the usefulness of D-dimer measurement during anticoagulation therapy has not been fully established, despite its widespread use. In this retrospective observational study, we investigated whether D-dimer measurement during anticoagulation therapy in cancer patients could predict overt VTE at follow-up. The study included patients who underwent D-dimer testing and contrast-enhanced computed tomography between 30 and 100 days after initiation of anticoagulation therapy. Eighty-two patients were included: 60 with cancer and 22 without. The diagnostic performance of D-dimer for overt VTE was as follows: sensitivity, 85.7%; specificity, 87.2%; positive predictive value, 78.3%; and negative predictive value, 89.2%. These findings suggest that D-dimer measurement at follow-up has high sensitivity and specificity for overt VTE in cancer patients and may aid in assessing thrombotic status. Clinically, if anticoagulation therapy is continued until D-dimer levels become negative, the absence of overt VTE could be inferred without additional invasive testing. No potential conflict of interest relevant to this article was reported.

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

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.<br> 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.<br> 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.

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

MDPI AG Acta Medica Okayama 2221-3759 14 1 2026 The Influence of Fluidic Flow Stress on the Development of the Secondary Palate 9 EN Masayo Nagata Department of Orthodontics, Okayama University Hospital Satoru Hayano Department of Orthodontics, Okayama University Hospital Ziyi Wang Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takahiro Kosami Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Kamioka Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Craniofacial development is orchestrated by a finely regulated interplay of numerous genes and signaling pathways. Palatogenesis proceeds through a complex, stepwise process, in which endogenous mechanical stresses within tissues have been implicated. However, the impact of exogenous fluidic flow mechanical stress derived from maternal movement on palatal development remains unclear. In this study, we investigated the effect of exogenous fluidic flow mechanical stress on palatal morphogenesis, focusing on the horizontal outgrowth of palatal shelves after elevation. Palatal tissues dissected from mouse embryos were subjected to organ culture with or without mechanical loading (loaded and unloaded groups, respectively). Stress magnitude was quantified by calculating wave energy, and morphometric and molecular analyses were performed. Compared with the unloaded group, palatal shelves in the loaded group showed significant increases in thickness and volume, accompanied by enhanced cell proliferation, nuclear translocation of YAP and β-catenin, and upregulation of the osteogenic markers Osterix and Osteocalcin. No significant difference in apoptosis was observed. These findings indicate that exogenous mechanical stress promotes cell proliferation and osteogenic differentiation through the Hippo and WNT/β-catenin pathways in palate explants. Our results suggest that moderate maternal movement-induced mechanical stress contributes to normal palatogenesis, providing new insights into the mechanisms underlying cleft palate. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1349-0079 68 1 2026 Insights into the taste of organic acids via TAS1Rs 100731 EN Yuko Yamase Department of Dental Anesthesiology and Special Care Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Katsuki Takebe Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kengo Horie Department of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihiro Mitoh Department of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsuko Yamashita Institute for Protein Research, The University of Osaka Ryusuke Yoshida Department of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: Organic acids contribute significantly to the flavor of fermented foods by imparting sourness. Although mice generally avoid sour taste, previous studies have reported greater consumption of l-lactic acid than its d-enantiomer, suggesting enantiomer-specific recognition. This behavior is hypothesized to involve TAS1Rs, which consists of sweet/umami receptors. However, it remains unclear whether TAS1Rs additionally contribute to the recognition of other chiral organic acids. This study aimed to evaluate the role of TAS1Rs, particularly TAS1R3, in the modulation of enantiomer-dependent behavioral responses to organic acids in mice.<br> Methods: Behavioral responses were evaluated using 48-h and 1-h 2-bottle tests. Binding of organic acids to TAS1Rs was investigated by differential scanning fluorimetry (DSF) with the ligand-binding domain (LBD) of medaka Tas1r2a/Tas1r3.<br> Results: Wild-type mice consumed more d-malic acid than l-malic acid in the 48-h test, whereas Tas1r3-KO mice showed no such difference. This pattern was not observed in the short-term 1-h test, which minimized the contribution of post-ingestion and learned effects. DSF analysis revealed no binding of any of the tested organic acids to the LBD of medaka Tas1r2a/Tas1r3.<br> Conclusions: Organic acids may elicit TAS1R3-dependent post-ingestion signals that contribute to enantiomer-selective consumption in mice. Electrostatic interactions and hydrogen-bonding networks within the orthosteric pocket of TAS1Rs may account for the differences in binding affinity to the LBD of medaka Tas1r2a/Tas1r3 between organic acids and L-alanine, a known ligand. 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.

Springer Science and Business Media LLC Acta Medica Okayama 1757-4749 18 1 2026 Sodium butyrate augments the antibacterial activity of tetracycline against clinical isolates of multidrug-resistant Vibrio cholerae 9 EN Sushmita Kundu Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections Sourin Alu Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections Abhishek Singh Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections Animesh Gope Division of General Medicine, ICMR- National Institute for Research in Bacterial Infections Ranjan Kumar Nandy Division of Bacteriology, ICMR- National Institute for Research in Bacterial Infections Asish K. Mukhopadhyay Division of Bacteriology, ICMR- National Institute for Research in Bacterial Infections Shin-ichi Miyoshi Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nabendu Sekhar Chatterjee Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections Sushmita Bhattacharya Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections Background Antibiotic resistance poses a major challenge in treating Vibrio cholerae infections. One promising method to counter resistance is the co-administration of antibiotics with non-antibiotic adjuvants to enhance their efficacy. This study investigated the combined action of sodium butyrate (SB) and tetracycline on tetracycline-resistant V. cholerae strains.<br> Results The combined activity of SB and antibiotics was assessed on eight V. cholerae clinical isolates using the Fractional Inhibitory Concentration Index (FICI), with SB-Tetracycline showing strong synergy (FICI: 0.09–0.5). Functional and mechanistic studies, including time-kill kinetics, live/dead staining, SEM-based morphological analysis, and fluorometric assays, demonstrated a synergistic antibacterial effect of SB and Tetracycline. This effect was associated with increased membrane permeability, disruption of membrane integrity, dissipation of the proton motive force, and suppression of efflux activity. These changes collectively led to membrane damage, enhanced intracellular accumulation of Tetracycline, decreased intracellular ATP levels, and ultimately, bacterial cell death. Moreover, GM1-CT ELISA and fluorescence microscopy revealed the synergistic anti-virulence activity of the SB- Tetracycline combination. Finally, the combination of SB and Tetracycline showed enhanced efficacy in animal models compared with monotherapy.<br> Conclusion: The observed SB-Tetracycline synergy provides a promising therapeutic approach to overcome tetracycline resistance in V. cholerae, offering a potential adjunct strategy for the management of antibiotic-resistant cholera infections. No potential conflict of interest relevant to this article was reported.

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

MDPI AG Acta Medica Okayama 1422-0067 26 12 2025 Specific Heat-Killed Lactic Acid Bacteria Enhance Mucosal Aminopeptidase N Activity in the Small Intestine of Aged Mice 5742 EN Takeshi Tsuruta Faculty of Environmental, Life, Natural Science and Technology, Okayama University Mami Wakisaka Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takumi Watanabe Bio-Lab Co., Ltd. Aoi Nishijima Faculty of Environmental, Life, Natural Science and Technology, Okayama University Akihito Ikeda Faculty of Environmental, Life, Natural Science and Technology, Okayama University Mao Teraoka Faculty of Environmental, Life, Natural Science and Technology, Okayama University Tianyang Wang Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kuiyi Chen Faculty of Environmental, Life, Natural Science and Technology, Okayama University Naoki Nishino Faculty of Environmental, Life, Natural Science and Technology, Okayama University Aminopeptidase N (APN), an enzyme expressed in the small intestinal mucosa, is involved in dietary protein digestion. Previous studies have shown that oral administration of fermented milk containing lactic acid bacteria (LAB) enhances mucosal APN activity in young mice. This study aimed to investigate whether LAB strains stimulate mucosal APN activity in aged mice and to evaluate its relevance to age-related changes in body composition. The underlying molecular mechanisms were also explored in vitro. Experiment 1: Aged C57BL/6J mice were fed diets supplemented with heat-killed LAB strains―Enterococcus faecalis OU-23 (EF), Leuconostoc mesenteroides OU-03 (LM), or Lactiplantibacillus plantarum SNK12 (LP). Compared to the aged Control group, the ileal APN activity was significantly higher in the LP group. LP administration also elevated serum Gla-osteocalcin levels and decreased serum CTX-1 levels. Experiment 2: IEC-6 cells were co-cultured with LP that had been treated with RNase, DNase, or lysozyme. APN activity was significantly lower in cells co-cultured with DNase- or lysozyme-treated LP compared to those co-cultured with untreated LP. A specific LAB strain may enhance mucosal APN activity in the aged intestine, potentially contributing to improved bone metabolism. This effect may be mediated by bacterial DNA and peptidoglycan. No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 『論語集注』訳注（子罕第九　（一）） (1) (20) EN Luyi SUN 10.18926/70032 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 大田植の分布と種類に関する検討（3）―岡山県・広島県の自治体史等における記述・資料― 1 18 EN Hiroshi TAKANO 10.18926/70017 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 表紙 EN No potential conflict of interest relevant to this article was reported.

Proceedings of the National Academy of Sciences Acta Medica Okayama 0027-8424 123 6 2026 A nuclear CobW/WW-domain factor represses the CO2-concentrating mechanism in the green alga Chlamydomonas reinhardtii e2518136123 EN Daisuke Shimamura Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Junko Yasuda Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Yosuke Yamahara Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Hirobumi Nakano Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Shin-Ichiro Ozawa Institute of Plant Science and Resources, Okayama University Ryutaro Tokutsu Graduate School of Science, Division of Biological Sciences, Kyoto University Ayumi Yamagami Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Tomonao Matsushita Graduate School of Science, Division of Biological Sciences, Kyoto University Yuichiro Takahashi Research Institute for Interdisciplinary Science, Okayama University Takeshi Nakano Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Hideya Fukuzawa Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Takashi Yamano Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Microalgae induce a CO2-concentrating mechanism (CCM) to maintain photosynthesis when CO2 is limited. Because this system consumes a substantial portion of photosynthetically generated ATP, its suppression when CO2 levels rise is critical for energy balance, yet the underlying mechanism remains unclear. Here, we identify a nuclear repressor of the CCM in the green alga Chlamydomonas reinhardtii. A pull-down screen for interacting partners of the master activator CCM1/CIA5 revealed an uncharacterized protein that tightly associates with CCM1. This protein, CCM1-binding protein 1 (CBP1), combines a CobW/CobW_C GTP-binding metallochaperone module with a WW-domain characteristic of protein–protein interactions. CBP1 colocalizes and interacts with CCM1 in the nucleus regardless of CO2 conditions. Disruption of CBP1 does not affect growth or CCM induction under CO2 limitation but derepresses 27 of 41 CCM1-dependent low-CO2 inducible genes under high-CO2 conditions. These include the periplasmic and intracellular carbonic anhydrases (CAH1 and LCIB) and inorganic carbon transporters/channels (LCIA, LCI1, BST1, and BST3). Consistently, cbp1 mutants accumulate CAH1 and LCIB proteins and exhibit 40% higher inorganic carbon affinity under high-CO2 conditions; this phenotype is rescued by CBP1 complementation or by acetazolamide treatment. Crucially, cbp1 mutants exhibit significant growth delays under high-CO2 conditions, especially when light is limiting, providing direct evidence that CBP1-mediated repression is essential for energy conservation. Thus, CBP1 prevents unnecessary CCM activity when CO2 is abundant, acting upstream of both transporter/channel and carbonic anhydrase modules. Our findings suggest a regulatory mechanism potentially linking zinc-dependent protein chemistry to CCM gene repression, providing insights into energy-efficient CO2 sensing in aquatic photosynthetic organisms. No potential conflict of interest relevant to this article was reported.

The Japan Institute of Heterocyclic Chemistry Acta Medica Okayama 0385-5414 70 1 2006 Synthesis of 6- and 7-(1,2,3-Trihydroxy-1,2-O-isopropylidenepropyl)pteridines and Deoxygenation of Their 3’-Hydroxy Groups 355 365 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Daisuke Takayama Department of Chemistry, Faculty of Science, Okayama University Hiroshi Yamamoto Department of Chemistry, Faculty of Science, Okayama University Treatment of 3,4-O-isopropylidene-L-threo-pentos-2-ulose (7) with 5,6-diamino-1,3-dimethyluracil (8) afforded 1,3-dimethyl-6-[(1R,2S)-1,2,3-trihydroxy-1,2-O-isopropylidenepropyl]lumazine (9a) and its 7-substituted isomer (9b). Deoxygenation of 3’-hydroxy groups of 9a,b was investigated in connection with a practical transformation of neopterin into biopterin. No potential conflict of interest relevant to this article was reported.

The Japan Institute of Heterocyclic Chemistry Acta Medica Okayama 0385-5414 69 1 2006 Synthesis of Functionalized Phospholane Oxides and Phosphorinane Oxides from 1,4- and 1,5-Di-O-Mesyloxy Compounds 283 294 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Karsten Schürrle Department of Chemistry, Faculty of Science, Okayama University Hiroshi Yamamoto Department of Chemistry, Faculty of Science, Okayama University Treatment of 1,4-di-O-mesyl-2,3-di-O-methyl-L-threitol (8b) with phenylphosphine in the presence of sodium hydride in DMSO, followed by the action of hydrogen peroxide, afforded 3,4-dimethoxy-1-phenylphospholane 1- oxide (7), while the same treatment of 1,5-di-O-mesyl-2,3,4-tri-O-methyl-meso- xylitol (11b) provided 2,3,4-trimethoxy-1-phenylphosphorinane 1-oxide (14). 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.

Springer Science and Business Media LLC Acta Medica Okayama 1349-4147 54 1 2026 Mycobacterium mageritense-associated refractory cutaneous infection and lymphadenitis in an immunocompetent adult: insights from genomic sequencing 19 EN Shinnosuke Fukushima Department of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Jumpei Uchiyama Department of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yoshio Kawakami Department of Dermatology, Okayama University Hospital Yoshiko Matsuura Konohana Dermatology Clinic Satoru Sugihara Department of Dermatology, Okayama University Hospital Shin Morizane Department of Dermatology, Okayama University Hospital Poowadon Muenraya Department of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background Nontuberculous mycobacteria are increasingly recognized as causes of chronic and refractory skin and soft tissue infections, even in individuals without immunodeficiency. Among them, Mycobacterium mageritense is a rare, rapidly growing species that can lead to persistent lesions requiring prolonged antimicrobial therapy. Reports of M. mageritense infections involving both the skin and regional lymph nodes are limited, and this case adds new clinical and genomic insights.<br> Case presentation A 48-year-old previously healthy man presented with a slowly enlarging cutaneous lesion on his lower leg and ipsilateral inguinal lymphadenitis. Empirical antibacterial therapy with β-lactams and macrolides was ineffective. Wound cultures subsequently grew M. mageritense, confirmed by whole-genome sequencing. Several antimicrobial regimens were attempted, and the final successful therapy consisted of oral levofloxacin and minocycline for 4 months, leading to complete clinical resolution. Genomic analysis identified resistance-related genes, including erm(40), aac(2′)-Ib, tet(V), and RbpA, although in vitro minimum inhibitory concentrations showed variable susceptibility. Phylogenetic comparison revealed that the isolate was closely related to previously reported M. mageritense strains from Japan.<br> Conclusions This case demonstrates that M. mageritense can cause cutaneous infection with secondary lymphadenitis in an immunocompetent host. Accurate species identification using molecular or genomic methods and selection of appropriate combination antibiotic therapy based on susceptibility testing are crucial for successful management of such infections. 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.<br> 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.<br> 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.<br> 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.<br> 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.

Springer Science and Business Media LLC Acta Medica Okayama 2059-3635 11 1 2026 Osimertinib inhibits the MYLK4-mediated phosphorylation of CDKAL1 to suppress stemness and chemoresistance in rhabdomyosarcoma 26 EN Takuto Itano Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rongsheng Huang Department of Cellular Physiology, 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 Eiji Nakata Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Fujimura Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 18 1 2026 Central Serous Chorioretinopathy in Parallel With Onset and Relapses of Minimal Change Nephrotic Syndrome: A 28-Year Case Follow-Up e102426 EN Toshihiko Matsuo Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Central serous chorioretinopathy is an idiopathic disease that manifests as one or several localized, small, dome-shaped serous retinal detachments on fundus examination. The pathophysiology involves fluid leakage from the choroidal capillaries, known as the choriocapillaris, into the subretinal space through sites of damage in the retinal pigment epithelium. This case report discusses the underlying causes of central serous chorioretinopathy-like findings in minimal change nephrotic syndrome.<br> <br> The patient was a 33-year-old woman who developed nephrotic syndrome that was confirmed to be minimal change disease by renal biopsy. She experienced two major relapses of nephrotic syndrome at the ages of 36 and 41 years. She also had a minor relapse at the age of 37 years, five months after the first major relapse at the age of 36 years, as well as four additional minor relapses at the ages of 44, 46, 50, and 51 years. The onset of central serous chorioretinopathy-like manifestations, which were localized to the left eye, occurred three months after the initial onset of nephrotic syndrome at the age of 33 years. Two subsequent episodes of relapse of central serous chorioretinopathy-like manifestations were observed in both eyes at intervals of five months and one month, respectively, after major relapses of nephrotic syndrome at the ages of 36 and 41 years. Thereafter, she did not develop further central serous chorioretinopathy-like manifestations.<br> <br> She discontinued oral prednisolone at the age of 54 years and experienced no further relapses of nephrotic syndrome through her latest visit at the age of 61 years. She maintained normal renal function and good visual acuity in both eyes. The long-term, consistent temporal association between episodes of central serous chorioretinopathy and the onset and relapses of minimal change nephrotic syndrome is strongly supported by longitudinal clinical observations spanning 28 years. This parallel course suggests a possible shared pathophysiological mechanism or common triggering factors underlying both diseases. 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).<br> 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.<br> 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.<br> 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.

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

BMJ Acta Medica Okayama 2044-6055 15 12 2025 Effectiveness of education programme to increase competency of health cadres in Indonesia: a cluster non-randomised controlled trial e095428 EN Dewie Sulistyorini Graduate School of Biomedical and Health Sciences, Hiroshima University K A T M Ehsanul Huq Graduate School of Biomedical and Health Sciences, Hiroshima University Abdulfatai Olamilekan Babaita Graduate School of Biomedical and Health Sciences, Hiroshima University Sadia A Aivey Graduate School of Biomedical and Health Sciences, Hiroshima University Gao Huiying Graduate School of Biomedical and Health Sciences, Hiroshima University Kana Kazawa Faculty of Health Sciences, Okayama University Yasuko Fukushima Graduate School of Biomedical and Health Sciences, Hiroshima University Mayumi Kako Graduate School of Biomedical and Health Sciences, Hiroshima University Michiko Moriyama Graduate School of Biomedical and Health Sciences, Hiroshima University Objectives Health cadres, who assist midwives in supporting pregnant women in community settings, need to enhance their competencies in identifying risk factors and referring high-risk pregnant women to midwives for further care. Since the capabilities of these health cadres are influenced by maternal complications, an educational programme was implemented to strengthen their skills. Therefore, this study aimed to evaluate the competency of health cadres by providing a researcher-developed educational programme.<br> Design An open-label, cluster non-randomised controlled trial.<br> Setting and participants Health cadres with at least 1 year of work experience were recruited at six public health centres (PHCs) in Banjarnegara Regency, Indonesia.<br> Interventions Six PHCs were selected and allocated into intervention group (IG=3 PHCs) and control group (CG=3 PHCs) groups. A total of 133 female health cadres were enrolled across the selected PHCs. At each PHC, a systematic random sampling method was used to select the participants. The researchers and health professionals provided a 3-week period of theoretical and scenario-based simulations to the IG, while the CG received no education.<br> Outcome measures Researcher-developed questionnaires and checklists were used to assess the knowledge, skills (health assessment, communication, attitude) and confidence. The primary endpoint was competency, a total score of knowledge and skills. The outcome domains were compared between the two groups, and a linear mixed-effect model was used to account for cluster-level variation.<br> Results A total of 130 (97.7%) completed the study (IG:64, CG:66). The competency score showed significant improvement at endline (CG=49.5 and IG=52.5; p=0.002). The median scores for health assessment skills (CG=12 vs IG=14; p<0.001) and communication skills (CG=7 vs IG=8; p<0.001) were increased in the IG compared with the CG. Mixed-effect model indicated that groups (β (95% CI) 2.49 (0.57 to 4.41), p=0.012), baseline knowledge (β(95% CI) 0.73 (0.54 to 0.92), p<0.001) and midline health assessment skills (β (95% CI) 0.54 (0.25 to 0.82), p<0.001) were significant positive predictors, while age was negatively associated with competency (β (95% CI) −0.20 (−0.30 to −0.10), p<0.001)).<br> Conclusion Education effectively increased the competency of health cadres. A well-structured education programme is necessary for health cadres to improve and maintain their competencies in monitoring high-risk pregnant women.<br> Trial registration number NCT06134518. No potential conflict of interest relevant to this article was reported.

The Japanese Society of Interventional Radiology Acta Medica Okayama 2432-0935 10 2025 Is Saline Sealing of Needle Tract Effective to Prevent Pneumothorax after Computed Tomography-guided Lung Biopsy? e2025-0068 EN Soichiro Okamoto Department of Radiology, Okayama University Hospital Yusuke Matsui Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Tomita Department of Radiology, Okayama University Hospital Kazuaki Munetomo Department of Radiology, Okayama University Hospital Noriyuki Umakoshi Department of Radiology, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose: To evaluate the efficacy of needle tract sealing using normal saline instillation for decreasing the risk of pneumothorax after computed tomography-guided lung biopsy.<br> Material and Methods: This retrospective, single-institution study included 391 computed tomography-guided lung biopsies performed by 12 operators between January 2022 and October 2024. After exclusion, 298 biopsies were analyzed by comparing the saline seal (n = 138) and control (n = 160) groups. A 17/18-gauge or 19/20-gauge coaxial biopsy system was used, and tract sealing was performed by instilling 1-5 mL of normal saline during the withdrawal of the introducer needle in the saline seal group; tract sealing was not performed in the control group. After 1:1 propensity score matching was performed to balance baseline characteristics, the incidences of pneumothorax and chest tube placement were compared between the two groups using Fisher's exact test.<br> Results: After propensity score matching, 108 pairs (mean lesion size: 17 mm) were well balanced. The incidence of pneumothorax did not differ significantly between the control and saline seal groups (50.0% vs. 60.2%, respectively; p = 0.171). Similarly, the incidence of chest tube placement was not significantly different between the two groups (7.4% vs. 13.0%, respectively; p = 0.260).<br> Conclusions: According to the propensity score-matched analysis, normal saline instillation for tract sealing did not significantly reduce the incidence of pneumothorax or chest tube placement. In our cohort, which had a high prevalence of small lesions, saline sealing alone may be insufficient to reduce post-biopsy pneumothorax risk. Hence, combined strategies require further investigation. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2211-1247 45 1 2026 Immunopeptidomics combined with full-length transcriptomics uncovers diverse neoantigens 116781 EN Takamasa Ishino Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences Tomofumi Watanabe Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences Serina Tokita Division of Cancer Immunology, Graduate School of Medical and Dental Sciences, Niigata University Youki Ueda Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences Katsushige Kawase Division of Cell Therapy, Chiba Cancer Center Research Institute Yuka Takano Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences Yin Min Thu Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences Yuta Suzuki Department of Computational Biology and Medical Sciences, The University of Tokyo Chie Owa Department of Computational Biology and Medical Sciences, The University of Tokyo Takashi Inozume Department of Dermatology, Chiba University Graduate School of Medicine Wenhao Zhou Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences Joji Nagasaki Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences Vitaly Kochin Department of Immunology, Nagoya University Graduate School of Medicine Toshihide Ueno Division of Cellular Signaling, National Cancer Center Research Institute Shinya Kojima Division of Cellular Signaling, National Cancer Center Research Institute Akiko Honobe-Tabuchi Department of Dermatology, University of Yamanashi Tatsuyoshi Kawamura Department of Dermatology, University of Yamanashi Takehiro Ohnuma Department of Dermatology, Kumamoto Kenhoku Hospital Takamitsu Matsuzawa Department of Dermatology, Chiba University Graduate School of Medicine Yu Kawahara Department of Dermatology, Chiba University Graduate School of Medicine Kazuo Yamashita KOTAI Biotechnologies, Inc Jason Lin Division of Cell Therapy, Chiba Cancer Center Research Institute Jun Koseki Division of Systems Biology, Nagoya University Graduate School of Medicine Hiroyoshi Nishikawa Department of Immunology, Nagoya University Graduate School of Medicine Motoo Araki Department of Urology, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences Naoya Kato Department of Gastroenterology, Graduate School of Medicine, Chiba University Teppei Shimamura Division of Systems Biology, Nagoya University Graduate School of Medicine Shinichi Morishita Department of Computational Biology and Medical Sciences, The University of Tokyo Yutaka Suzuki Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo Hiroyuki Mano Division of Cellular Signaling, National Cancer Center Research Institute Toshihiko Torigoe Takayuki Kanaseki Division of Cancer Immunology, Graduate School of Medical and Dental Sciences, Niigata University Masahito Kawazu Division of Cell Therapy, Chiba Cancer Center Research Institute Yosuke Togashi Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences Neoantigens are crucial for antitumor immunity and immune checkpoint inhibitor (ICI) efficacy by triggering strong immune responses. However, conventional methods for identifying neoantigens, such as whole-exon sequencing and short-read RNA sequencing (RNA-seq), appear to be insufficient, and the tumor mutational burden cannot sufficiently predict ICI efficacy. In this study, we employed a proteogenomic approach using long-read RNA-seq with Pacific Biosciences Single-Molecule Real-Time Sequencing technology to analyze full-length transcripts in combination with the human leukocyte antigen ligandome. As a result, many neoantigen candidates were identified, which were unregistered in a comprehensive database, including those from non-coding regions. Additionally, we validated the responses of specific T cell receptors (TCRs) to these candidates and identified several pairs of TCRs and neoantigens. These findings highlight the presence of more diverse neoantigens than expected that cannot be identified by conventional methods. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2025 Salivary short chain fatty acids serve as biomarkers of periodontal inflammatory burden 1786 EN Kazu Takeuchi-Hatanaka Division of Periodontics and Endodontics, Department of Dentistry, Okayama University Hospital Yasushi Shirahase Sysmex Corporation Toshiyuki Yoshida Sysmex Corporation Mari Kono Sysmex Corporation Naoki Toya Sysmex Corporation Kenji Konishi Present address: Diagnostics Division, IVD Enzyme Department, Nagase Diagnostics Kazuhiro Omori Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Takashiba Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Periodontitis is a chronic inflammatory condition associated with systemic diseases. Early detection and intervention are crucial; however, conventional diagnostic methods require specialized dental procedures. Therefore, we aimed to develop a noninvasive saliva-based screening method that can be easily performed outside dental clinics. This cross-sectional pilot study evaluated three periodontal indices―probing depth, Periodontal Inflamed Surface Area (PISA), and periodontal epithelial surface area―in relation to short-chain fatty acids (SCFAs) and bacterial profiles in the saliva. Saliva samples collected during the day exhibited stronger correlations with periodontal indices than waking time samples, demonstrating a significant association with periodontal pathogens, protease activity, and elevated levels of butyric acid. The diagnostic thresholds for PISA were 300 mm2 and 600 mm2. Multivariate logistic regression and likelihood ratio analyses identified the combination of enzymatic SCFA markers and dipstick-based occult blood or leukocyte detection as a promising biomarker pair. Combining enzymatic SCFA markers with occult blood demonstrated a positive likelihood ratio of 3.4 and a negative likelihood ratio of 0.19 for PISA ≥ 600 mm2, with a post-test probability of 77%, sensitivity of 86%, and specificity of 75%. These findings suggest that combining salivary enzymatic and dipstick-based biomarkers provides a simple, cost-effective, and moderately informative screening strategy for periodontitis. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2328-8957 13 1 2025 Impact of Candida Care Bundle Compliance on the Prognosis of Patients With Candidemia: A Multicenter Retrospective Cohort Study With Propensity Score Matching Analysis (2016–2023) ofaf790 EN Hidemasa Akazawa Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Toshie Higuchi Department of General Internal Medicine, Okayama Red Cross Hospital Tomoko Miyoshi Center for Medical Education and Internationalization, Kyoto University Graduate School of Medicine Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Yukinobu Akamatsu Department of General Medicine, Tottori Municipal Hospital Yuto Haruki Department of Pharmacy, Tsuyama Chuo Hospital Yoshitaka Iwamoto Department of General Medicine, NHO Okayama Medical Center Shuichi Tanaka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shun Fujisato Department of Pharmacy, Okayama Rousai Hospital Soichiro Ako Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background. Candidemia is a life-threatening infection with high mortality, and appropriate management is essential to improve patient outcomes. The Candida Care Bundle aims to standardize hospital management for patients with candidemia and reduce mortality.<br> Methods. This retrospective multicenter cohort study included candidemia cases from 9 hospitals in Japan between 2016 and 2023. Compliance to the Candida Care Bundle was evaluated based on 5 elements: central venous catheter removal within 24 hours, appropriate antifungal therapy, ophthalmologic examination, follow-up blood cultures, and antifungal treatment for ≥2 weeks after clearance. Patients were categorized into high (4–5 items) and low (0–3 items) compliance groups. The primary and secondary outcomes were defined as 30-day survival and the development of endophthalmitis, with propensity score matching used to adjust for potential confounders.<br> Results. Among 230 patients, 160 (69.5%) were classified into the high compliance group, which exhibited significantly lower 30-day mortality than the low compliance group (8.8% vs 57.1%, P < .01). Even after matching, the high compliance group remained independently associated with improved survival (hazard ratio [HR]: 0.15; 95% confidence interval [CI]: .08–.30). C. albicans (HR: 1.95; 95% CI: 1.01–3.52) and central line-associated bloodstream infection (HR: 2.63; 95% CI: 1.35–5.12) were associated with the fatal outcome. Endophthalmitis involved 23.6% of the patients, being associated with C. albicans (odds ratio [OR]: 8.18; 4.46–19.30) and central line-associated bloodstream infection (OR: 2.69; 1.08–6.70).<br> Conclusions. Strict compliance to the Candida Care Bundle significantly improves survival, underscoring its importance in candidemia management. No potential conflict of interest relevant to this article was reported.

Open Library of the Humanities Acta Medica Okayama 2056-6700 12 1 2026 Racialized Contagion and Defensive Biopolitics in The Last of Us EN Robert Yeates Faculty of Humanities and Social Sciences, Okayama University In the opening moments of the video game The Last of Us Part I, players are introduced to an emerging pandemic via Austin’s Texas Herald newspaper. Below a headline warning of mass hospitalizations from a 'mysterious infection', players read of a recall of imported crops 'potentially tainted with mold': 'Initial lists distributed to vendors nationwide warned against crops imported from South America. However now the scope has extended to include Central America and Mexico'. This scene immediately suggests the racialization of the franchise’s Cordyceps brain infection (CBI), with the contagion germinating in the global South, invading the US via its southern border, and spreading fastest in the nation’s diverse urban centres. By highlighting tainted crops as the vector of dispersal in the US, however, rather than infected humans, the franchise resists making this a simple invasion-scare narrative and instead suggests that the spread of the infection is in part a result of the capitalist exploitation of cheap land and labour in the global South. Despite its inconsistent record on racial representation and the near-absence of discussion of race across the franchise, the structures reflecting the racialization of contagion and the perpetuation of racialized hierarchies through defensive biopolitics remain present. Drawing connections with the discourse around immigration and the southern border and contemporary pandemics and epidemics, this article makes the case for reading the franchise in terms of racialized contagion and defensive biopolitics, a reading that highlights how the games and their television adaptation reflect urgent contemporary issues around race in America. No potential conflict of interest relevant to this article was reported.

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 49 1 2026 Exploratory Analysis for Development Predictive Models of Immune Checkpoint Inhibitor-Induced Myocarditis Using a Nationwide Claims Database 66 73 EN Reina Yamamoto Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Koki Nakagomi Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Miyu Uchiyama Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Ayana Michihara Department of Pharmacy, Okayama University Hospital Aya F. Ozaki Department of Clinical Pharmacy Practice, School of Pharmacy &amp; Pharmaceutical Sciences, University of California Pranav M. Patel Division of Cardiology, School of Medicine, University of California Maki Tanioka Medical AI Project, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Yoshito Zamami Department of Pharmacy, Okayama University Hospital Takashi Uehara Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Immune checkpoint inhibitors (ICIs), essential in cancer therapy, can cause severe immune-related adverse events (irAEs), including myocarditis with a high fatality rate. Currently, the pathogenesis, biomarkers, and risk factors of ICI-induced myocarditis (ICIM) are not fully understood. This exploratory study aimed to develop machine learning-based models to predict the onset of ICIM within 3 months of starting ICI therapy, using a large health insurance database. The models were constructed using the Light Gradient Boosting Machine (LightGBM) and Random Forest algorithms, incorporating clinical variables such as comorbidities and prior medication classifications. In this study, a strategy combining undersampling and bagging was used to minimize the impact of highly imbalanced datasets. The Random Forest model demonstrated superior performance compared with the LightGBM model, and the SHapley Additive exPlanations (SHAP) analysis for the Random Forest model revealed that the concurrent use of ICIs was the most important variable for predictions. Although predictive performance remains limited (AUROC ≈ 0.63), this exploratory framework demonstrates the feasibility of developing data-driven risk prediction models for ICIM. Future studies with expanded datasets and integration of laboratory parameters are warranted to improve predictive accuracy and potential clinical applicability. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0014-4800 145 2026 Assessing the role of folate syntrophy and folate cross-feeding in the pathobiology of infectious-inflamed milieu caused by Fusobacterium nucleatum 105021 EN Darab Ghadimi Department of Microbiology and Biotechnology, Max Rubner-Institut Sophia Blömer Faculty of Medicine, Christian-Albrechts-University of Kiel Aysel Şahin Kaya Department of Nutrition and Dietetics, Faculty of Health Sciences, Antalya Bilim University Sandra Krüger Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein Christoph Röcken Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein Heiner Schäfer Laboratory of Molecular Gastroenterology & Hepatology, Christian-Albrechts-University & UKSH Campus Kiel Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Shigenobu Matsuzaki Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University Wilhelm Bockelmann Department of Microbiology and Biotechnology, Max Rubner-Institut Diet and nutrition affect almost every biological process, including multiple chronic diseases, diabetes, and some cancers. However, there are still significant gaps in our understanding of the importance of nutrition and healthy diets in syntrophy with respect to cross-feeding of the microbe-microbe and the microbe-host in the pathobiology of the infectious-inflamed intestinal milieu caused by anaerobic opportunistic bacteria such as Fusobacterium nucleatum (F. nucleatum). We examined the immune outcomes of three-member folate syntrophy and cross-feeding between F. nucleatum bacteria, endogenous folate-producing gut bacteria, and host cells at the host-pathogen interface using a triple co-culture model. T84, THP-1, and Huh7 cells were inoculated with F. nucleatum for 6 h in regular DMEM, DMEM with 9.5 μM folic acid, or with/without a mixture of Bifidobacterium longum subsp. infantis (B. infantis) and Escherichia coli Nissle 1917 (EcN). Cytokine secretion, cometabolite levels (ammonia, indoles), cell viability, and barrier integrity were assessed. F. nucleatum-induced folate depletion was associated with increased IL-1β and IL-6 and decreased IL-22, along with reduced transepithelial electrical resistance (TEER) and cell viability in T84 cells. Folate supplementation mitigated these effects. The mixture of B. infantis and EcN reduced F. nucleatum-induced pro-inflammatory cytokines, increased IL-22, and improved TEER and cell viability. These protective effects were enhanced by the addition of folate. F. nucleatum also elevated ammonia and reduced indoles, effects reversed by B. infantis and EcN. In addition to the intrinsic pathogenicity of harmful bacteria, folate deprivation, microbe–microbe folate syntrophy, and microbe–host folate cross-feeding contribute to the pathobiology of anaerobic opportunistic bacteria and influence the physiological fate of host cells. A combination of B. infantis and EcN modulates the infectious-inflamed interface through a cytoprotective effect and mechanical competitive extrusion of pathogenic F. nucleatum. These results provide potential insights into the mechanisms of early-onset colorectal cancer, and evidently, require future studies using patient-derived organoids and in vivo systems to improve clinical relevance. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 18 1 2026 Endoscopic Topical Application (ETA) Therapy for Refractory Overactive Bladder: A First-in-Human Report e101143 EN Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Sugihara Department of Surgery, Nishi Fukuyama Hospital Yosuke Mitsui Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toyohiko Watanabe 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 Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Refractory overactive bladder (OAB) remains a clinical challenge despite established therapies, such as anticholinergics, β3-agonists, and intradetrusor botulinum toxin (BTX). Emerging evidence suggests that sensory mechanisms within the bladder, including those involving the trigone where superficial afferent networks are present, may contribute to persistent urinary urgency and frequency in some patients. Although intradetrusor BTX injection is effective in selected patients, its impact on these superficial pathways may be limited because the injected drug predominantly distributes within the detrusor. Endoscopic topical application (ETA) therapy delivers BTX directly to the trigone under air cystoscopy, potentially providing targeted modulation of sensory hyperexcitability. We report a 72-year-old woman with long-standing refractory OAB who experienced only partial improvement with repeated intradetrusor BTX injections but achieved clinically meaningful symptom relief after ETA therapy. Nocturia, urgency, urgency urinary incontinence, and voided volume were improved, with no complications other than transient postoperative urethral pain. This case suggests that ETA therapy may represent a promising sensory-focused option for refractory OAB. 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.<br> 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.<br> 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.<br> 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.<br> 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.

Japan Oil Chemists' Society Acta Medica Okayama 1345-8957 74 11 2025 Bioconversion and Metabolic Fate of the n-1 Polyunsaturated Fatty Acids, 6,9,12,15- Hexadecatetraenoic (C16:4 n-1) and 8,11,14,17- Octadecatetraenoic (C18:4 n-1) Acids, in HepG2 Cells 1023 1032 EN Koki Sugimoto Faculty of Food and Nutritional Sciences, Toyo University Hideto Nishiguchi Faculty of Chemistry, Materials, and Bioengineering, Kansai University Ryota Hosomi Faculty of Chemistry, Materials, and Bioengineering, Kansai University Toshifumi Tanizaki Bizen Chemical Co., Ltd. Tadahiro Tsushima Bizen Chemical Co., Ltd. Naomichi Baba Bizen Chemical Co., Ltd. Yoshihisa Misawa Bizen Chemical Co., Ltd. Ziyi Wang Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuaki Ono Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Murakami Department of Hygiene and Public Health, Kansai Medical University Seiji Kanda Department of Hygiene and Public Health, Kansai Medical University Kenji Fukunaga Faculty of Chemistry, Materials, and Bioengineering, Kansai University Fish oil contains not only major fatty acids with double bonds at the n-3, n-6, n-7, and n-9 positions but also those with a double bond at the n-1 position, such as 6,9,12,15-hexadecatetraenoic acid (C16:4 n-1; HDTA). However, intracellular bioconversion and metabolic fate of n-1 polyunsaturated fatty acids (PUFA) remain unclear. Therefore, in this study, we aimed to assess the intracellular bioconversion and metabolic fate of HDTA and its metabolite, 8,11,14,17- octadecatetraenoic acid (C18:4 n-1; ODTA), using HepG2 cells. Based on the results of cell viability and cytotoxicity assays for HDTA and ODTA, the concentration of each fatty acid supplemented in the experiments was set at 10 μM. HepG2 cell culture with HDTA revealed C20:4 n-1 as a new HDTA metabolite, along with previously reported ODTA. Our findings suggest that the HDTA taken up by HepG2 cells undergoes elongation to form ODTA and C20:4 n-1. Following supplementation with HDTA, ODTA, and 5,8,11,14,17-eicosapentaenoic acid (C20:5 n-3; EPA), fatty acids disappeared from the culture medium within 24 h. Notably, the total relative level of HDTA and its metabolites, including ODTA and C20:4 n-1 in HDTA- and ODTA-supplemented cells were significantly lower than the total relative level of EPA and its metabolites, including 7,10,13,16,19-docosapentaenoic acid (C22:5 n-3), C24:6 n-3, and 4,7,10,13,16,19-docosahexaenoic acid (C22:6 n-3) in the EPA-supplemented cells. Except for a portion that was intracellularly elongated, most HDTA was taken up by HepG2 cells and may undergo rapid fatty acid β-oxidation. However, RNA-sequencing and real-time polymerase chain reaction analysis revealed no significant changes in fatty acid β-oxidation–related gene expression levels in HDTA-supplemented cells. Collectively, these results provide novel insights into the intracellular bioconversion mechanisms and metabolic fate of HDTA and ODTA in HepG2 cells, suggesting that the metabolic fate of n-1 PUFA is distinct from that of common PUFA. No potential conflict of interest relevant to this article was reported.

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

MDPI AG Acta Medica Okayama 2313-433X 12 1 2025 FluoNeRF: Fluorescent Novel-View Synthesis Under Novel Light Source Colors and Spectra 16 EN Lin Shi Department of Artificial Intelligence, Kyushu Institute of Technology Kengo Matsufuji Department of Artificial Intelligence, Kyushu Institute of Technology Michitaka Yoshida Department of Computer Science, Okayama University Ryo Kawahara Graduate School of Informatics, Kyoto University Takahiro Okabe Department of Computer Science, Okayama University Synthesizing photo-realistic images of a scene from arbitrary viewpoints and under arbitrary lighting environments is one of the important research topics in computer vision and graphics. In this paper, we propose a method for synthesizing photo-realistic images of a scene with fluorescent objects from novel viewpoints and under novel lighting colors and spectra. In general, fluorescent materials absorb light with certain wavelengths and then emit light with longer wavelengths than the absorbed ones, in contrast to reflective materials, which preserve wavelengths of light. Therefore, we cannot reproduce the colors of fluorescent objects under arbitrary lighting colors by combining conventional view synthesis techniques with the white balance adjustment of the RGB channels. Accordingly, we extend the novel-view synthesis based on the neural radiance fields by incorporating the superposition principle of light; our proposed method captures a sparse set of images of a scene from varying viewpoints and under varying lighting colors or spectra with active lighting systems such as a color display or a multi-spectral light stage and then synthesizes photo-realistic images of the scene without explicitly modeling its geometric and photometric models. We conducted a number of experiments using real images captured with an LCD and confirmed that our method works better than the existing methods. Moreover, we showed that the extension of our method using more than three primary colors with a light stage enables us to reproduce the colors of fluorescent objects under common light sources. 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.

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

Spandidos Publications Acta Medica Okayama 2049-9450 23 5 2025 Prolonged exposure to axitinib alters the molecular profile of Caki‑2 renal cell carcinoma cells 101 EN Yuko Nakayama Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University Aya Ino Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University Kazuhiro Yamamoto Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohji Takara Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University Axitinib, an oral second‑generation multitargeted tyrosine kinase inhibitor, is used as a second‑line treatment for metastatic renal cell carcinoma (RCC). However, patients often develop resistance after initial responsiveness, necessitating the elucidation of the underlying resistance mechanisms. Therefore, the present study aimed to investigate the mechanisms underlying axitinib resistance using the Caki‑2 human papillary RCC model cells. Cells tolerating 0.1 µM axitinib were designated as Caki/AX cells. Cell viability was assessed using the water‑soluble tetrazolium salt assay. Notably, the 50% inhibitory concentration (IC50) values of axitinib and sunitinib were significantly higher in Caki/AX cells than those in Caki‑2 cells, indicating 2.83‑ and 1.2‑fold resistance, respectively. By contrast, the IC50 values of sorafenib and erlotinib were decreased in Caki/AX cells. Moreover, Caki/AX cells showed resistance to everolimus, temsirolimus and rapamycin, and decreased sensitivity to vinblastine, vincristine, paclitaxel, doxorubicin and SN‑38 compared with Caki‑2 cells. Notably, etoposide, 5‑fluorouracil, cisplatin and carboplatin sensitivities were comparable in both cell types. Reverse transcription‑quantitative polymerase chain reaction (PCR) analysis revealed that the mRNA levels of the ATP‑binding cassette subfamily B member 1 and subfamily G member 2 were significantly higher in Caki/AX cells than those in Caki‑2 cells. A PCR array related to vascular endothelial growth factor signalling showed that the mRNA levels of FIGF (also known as vascular endothelial growth factor D) and sphingosine kinase 1 were upregulated, whereas those of Rac family small GTPase 2 were downregulated in Caki/AX cells. Overall, these findings suggested that the upregulation of the ATP‑binding cassette subfamily B member 1, FIGF and sphingosine kinase 1 mRNA levels, and downregulation of the Rac family small GTPase 2 mRNA levels may contribute to acquired resistance in Caki/AX cells. No potential conflict of interest relevant to this article was reported.

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

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

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

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.<br> 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.<br> 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.<br> 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.

Springer Science and Business Media LLC Acta Medica Okayama 0300-8126 2025 Hospital-acquired pneumonia caused by multidrug-resistant Streptococcus pneumoniae serotype 15A EN Hidemasa Akazawa 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 Madoka Shimbe Department of Infectious Diseases, Okayama University Hospital Bin Chang Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security Yukihiro Akeda Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background Streptococcus pneumoniae remains a common cause of community-acquired pneumonia but is an infrequent pathogen in hospital-acquired pneumonia (HAP). Non-vaccine serotypes of multidrug-resistant (MDR) S. pneumoniae strains have been emerging globally, posing an increased risk of nosocomial infection.<br> Case A 71 year-old man developed pneumonia on postoperative day 4 following spinal fusion surgery. Despite initial treatment with ampicillin/sulbactam, his condition deteriorated, requiring ICU admission and mechanical ventilation. Microbiological testing confirmed S. pneumoniae as a causative pathogen, and ceftriaxone was empirically administered based on the local antibiogram. However, antimicrobial susceptibility testing revealed resistant profiles to penicillin (minimum inhibitory concentration [MIC], 8 µg/mL), ceftriaxone (MIC, 16 µg/mL), meropenem (MIC, 1 µg/mL), macrolides, and clindamycin, while demonstrating susceptibility to levofloxacin and vancomycin. The therapeutic regimen was subsequently adjusted to levofloxacin, resulting in clinical improvement. The isolate was later identified as serotype 15A, sequence type 63 (ST63).<br> Conclusion This case highlights that MDR S. pneumoniae can cause early-onset HAP and may not be covered by standard empiric therapies, emphasizing the need for careful evaluation of treatment response. Continued surveillance of infections caused by vaccine-escape clones like MDR serotype 15A is essential, given their increasing clinical relevance. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0301-486X 190 6 2025 Prognostic Value of Serum (1→3)-β-D-Glucan Levels in Patients with Candidemia Stratified by Compliance with Candida Bundle: A Multicenter Retrospective Cohort Study (2016–2023) 90 EN Hidemasa Akazawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Toshie Higuchi Department of General Internal Medicine, Okayama Red Cross Hospital Tomoko Miyoshi Center for Medical Education and Internationalization, Kyoto University Graduate School of Medicine Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Yukinobu Akamatsu Department of General Medicine, Tottori Municipal Hospital Yuto Haruki Department of Pharmacy, Tsuyama Chuo Hospital Yoshitaka Iwamoto Department of General Medicine, NHO Okayama Medical Center Shuichi Tanaka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shun Fujisato Department of Pharmacy, Okayama Rousai Hospital Soichiro Ako Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background Candidemia is a severe systemic infection with a high mortality risk. While β-D-glucan (BDG) serves as a diagnostic biomarker, its prognostic value in candidemia, particularly in association with Candida bundle compliance, remains unclear.<br> Methods In this retrospective multicenter cohort study, we evaluated 96 patients with candidemia across nine Japanese hospitals between 2016 and 2023. Candida bundle compliance was assessed using five key components: central venous catheter removal within 24 h of diagnosis, appropriate initial antifungal therapy, ophthalmologic examination, follow-up blood cultures until clearance, and antifungal therapy for at least two weeks post-clearance. Analyses stratified patients by serum BDG status (positive/negative) and compliance with the Candida bundle (high: 4–5 points; low: 0–3 points). The primary outcome was 30-day mortality, and the secondary outcome was defined as endophthalmitis incidence.<br> Results Of 96 eligible patients with candidemia, 70 (72.9%) were BDG-positive and 26 (27.1%) were BDG-negative. The overall 30-day mortality was 17.7%. Among BDG-positive patients, 15 (21.4%) died, while 2 (7.7%) died in BDG-negative cohorts (p = 0.09). Serum BDG positivity demonstrated a statistically significant association with decreased survival rates in the low bundle adherence group (p = 0.02), whereas this correlation was not observed among patients in the high-compliance cohort (p = 0.66). Endophthalmitis occurred in 25.0% of patients, without significant correlation to serum BDG status. C. albicans was associated with a significantly higher incidence of endophthalmitis compared with non-albicans species (45.7% vs. 8.9%).<br> Conclusions Serum BDG positivity potentially correlates with worse survival in candidemia, particularly in patients with low bundle compliance. This emphasizes the importance of adherence to standardized Candida management protocols for optimizing patient outcomes. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2688-1152 6 1 2025 Severe Intracranial Infection 100026 EN Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Takumi Fujimori Microbiology Division, Clinical Laboratory, Okayama University Hospital Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 15 1 2026 Oral Health-Related Quality of Life and Self-Reported Oral Health Status Are Associated with Change in Self-Reported Depression Status: A Cohort Study 376 EN Noriko Takeuchi Department of Preventive Dentistry, Division of Dentistry, Medical Development Field, Okayama University Takayuki Maruyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoki Toyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuzuki Katsube Dental School, Okayama University Takahiro Tabuchi Division of Epidemiology, School of Public Health, Tohoku University Graduate School of Medicine Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Oral health-related quality of life (OHRQoL) may influence mental health outcomes, yet longitudinal evidence on its association with depression remains limited. This study aimed to examine whether oral health status and OHRQoL are associated with a change in self-reported depression status among adults in Japan. Methods: We analyzed data from the Japan COVID-19 and Society Internet Survey (JACSIS), conducted in 2022 and 2023. A total of 15,068 participants aged ≥20 years without depression at baseline were included. Depression status was identified by self-reported measures between the two survey waves. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for change in self-reported depression status in relation to OHRQoL and oral health status, adjusting for sociodemographic and behavioral factors. Results: During follow-up, 218 participants (1.45%) reported a change in self-reported depression status. Poorer OHRQoL was significantly associated with a change in self-reported depression status (OR: 1.018; 95% CI: 1.001–1.036; p = 0.039). Additional risk factors included younger age (OR: 0.974; 95% CI: 0.964–0.985), participation in hobbies and cultural activities (OR: 2.224; 95% CI: 1.498–3.302), habitual use of sleeping pills or anxiolytics (current use OR: 3.512; 95% CI: 2.267–5.442), increased loneliness (OR: 1.217; 95% CI: 1.140–1.299), lower life satisfaction (OR: 0.900; 95% CI: 0.836–0.969), and poor self-rated health (OR: 2.921; 95% CI: 1.810–4.715). Conclusions: Impaired OHRQoL was associated with a change in self-reported depression status, potentially through psychosocial mechanisms. These findings suggest that oral health and OHRQoL may be relevant factors to consider in integrated oral and mental health approaches in clinical practice. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2079-6374 16 1 2026 Magnetic Detection of Cancer Cells Using Tumor-Homing Peptide-Modified Magnetic Nanoparticles 45 EN Shengli Zhou Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yuji Furutani Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kei Yamashita Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Sakuya Kako Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kazunori Watanabe Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toshihiko Kiwa Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takashi Ohtsuki Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Magnetic nanoparticles (MNPs) provide a platform for target detection because of their magnetic responsiveness to alternating magnetic fields (AMFs). We developed a detection method using MNPs modified with tumor-homing peptides (THPs), PL1 and PL3, which selectively bind to protein components enriched in malignant tissues. THP-MNPs were synthesized using maleimide-PEG-NHS linkers and characterized using transmission electron microscopy. Human glioblastoma cancer U87MG and normal tissue-derived HEK293 cells were incubated with THP-MNPs, and the magnetic signals were measured using a high-temperature superconducting quantum interference device (SQUID) magnetometer under an AMF (1.06 kHz). Dark-field microscopy confirmed the preferential binding of THP-MNPs to U87MG cells. In the absence of cells, THP-MNPs exhibited AMF-dependent signal enhancement, which correlated with particle size reduction due to THP release. This increase was completely suppressed in the presence of U87MG cells, indicating a strong THP-mediated interaction. PL3-MNPs exhibited superior discrimination between malignant and non-malignant cells. These results demonstrate that SQUID-based magnetic measurements using THP-MNPs enable rapid and label-free cancer cell detection. No potential conflict of interest relevant to this article was reported.

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

American Society for Microbiology Acta Medica Okayama 0066-4804 69 12 2025 Genomic portrayal of emerging carbapenem-resistant El Tor variant Vibrio cholerae O1 e00740-25 EN Sreeja Shaw ICMR-National Institute for Research in Bacterial Infections Agila Kumari Pragasam V. Ramalingaswami Bhawan, Indian Council of Medical Research Goutam Chowdhury ICMR-National Institute for Research in Bacterial Infections Prosenjit Samanta ICMR-National Institute for Research in Bacterial Infections Deboleena Roy ICMR-National Institute for Research in Bacterial Infections Debjani Ghosh ICMR-National Institute for Research in Bacterial Infections Thandavarayan Ramamurthy ICMR-National Institute for Research in Bacterial Infections Jigna Karia Medical College Baroda Govind Ninama Medical College Baroda Shin-ichi Miyoshi Okayama University Yukihiro Akeda National Institute of Infectious Diseases Hemanta Koley ICMR-National Institute for Research in Bacterial Infections Asish Kumar Mukhopadhyay ICMR-National Institute for Research in Bacterial Infections The escalating prevalence of carbapenem-resistant (CR) enteric pathogens elicits significant challenges to public health management and effective antimicrobial therapy. While carbapenem resistance is rare in Vibrio cholerae O1 (VC), the recent emergence of CR strains reveals a concerning shift in their antimicrobial resistance (AMR) landscape. This study aims to characterize the resistance mechanisms in newly identified El Tor CRVC isolated from cholera patients in Gujarat, India during 2019. Fifty VC isolates were screened for major virulence-associated genes along with the determination of their antibiotic resistance profiles using Kirby-Bauer disk diffusion and MIC assays. Whole-genome sequencing (WGS) was employed to investigate the underlying mechanisms of CR. All the isolates exhibited hypervirulent Haitian alleles of major virulence genes and AMR profiles of typical multidrug resistance (MDR). Strikingly, 12% (6/50) of them were resistant to carbapenems and other antibiotics. Molecular analysis revealed that these CR isolates were clonally related and harbored a 142 kbp IncA/C type conjugative mega-plasmid with several AMR encoding genes, including blaNDM-1, that can be easily transferred to other bacterial species and confer donor AMR patterns. The plasmid’s competence for horizontal gene transfer presents a significant risk of dissemination to other enteric pathogens and thereby may complicate the treatment. This finding emphasizes the urgent need for enhanced genomic surveillance and robust antimicrobial stewardship programs aimed at curbing the spread of CRVC strains and mitigating their impact on cholera treatment and containment strategies. No potential conflict of interest relevant to this article was reported.

Ceramic Society of Japan Acta Medica Okayama 1348-6535 134 1 2026 Structural and spectroscopic characterization of keatite (SiO2) 1 4 EN Masami Kanzaki Institute for Planetary Materials, Okayama University Xianyu Xue Institute for Planetary Materials, Okayama University Keatite, a polymorph of silica rare in nature, was synthesized by hydrothermal treatment of silicon and water at 100 MPa and 600 °C. The crystal structure of keatite at 24 °C was refined by the Rietveld method using synchrotron X-ray diffraction data. The obtained structure is consistent with the results of previous studies in which some constraints were imposed during refinements. The 29Si MAS NMR spectrum of keatite shows two peaks at −113.9 and −114.3 ppm, which can be assigned to Si at the Si1 and Si2 sites, respectively. The Raman spectrum of keatite shows a prominent peak at 473 cm−1, which is attributable to the Si–O–Si bending mode of the 5-membered ring. These spectra, reported for the first time, are expected to be valuable for the identification of keatite in synthetic and natural samples. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-0851 75 1 2025 Gut microbial metabolite butyrate boosts p53-expressing telomerase-specific oncolytic adenovirus efficacy by enhancing infectivity and activating MHC-I/cGAS-STING 10 EN Masaki Sakamoto 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 Tetsuya Katayama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yu Mikane Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunya Hanzawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Kadowaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Hamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoma Sugimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiaki Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi 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 Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The gut microbiota plays an essential role in regulating host immunity, and its metabolites such as butyrate exert immunomodulatory effects by acting as histone deacetylase inhibitors. Oncolytic virotherapy has emerged as a promising approach for cancer treatment, and we have developed OBP-702, a telomerase-specific oncolytic adenovirus that expresses p53 and elicits strong systemic antitumor responses. In this study, the potential synergy between butyrate and OBP-702 was investigated in colorectal cancer models. Using human and murine colorectal carcinoma cell lines, butyrate was found to directly enhance the infectivity of OBP-702 by upregulating CAR and integrins, thereby promoting apoptosis and autophagy in tumor cells. In addition, butyrate indirectly boosted systemic antitumor immunity by upregulating MHC-I expression through activation of the cGAS-STING pathway and enhancing CD8 + T cell recruitment via CXCL10 secretion. These findings were supported by in vivo experiments using CT26 subcutaneous, bilateral, and orthotopic tumor models, in which the combination of oral butyrate and intratumoral OBP-702 administration produced synergistic antitumor effects. These results highlight the therapeutic potential of integrating gut microbial metabolites with oncolytic virotherapy as a novel immunotherapeutic strategy for colorectal cancer. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 137 3 2025 令和６年度岡山医学会賞　がん研究奨励賞（林原賞・山田賞） 89 91 EN Shota Takihira Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0006-2960 64 20 2025 Characterization of Autonomous and Ca2+/Calmodulin-Dependent Activities of CaMKK Isoforms In Vitro and in Mouse Tissues 4309 4317 EN Satomi Ohtsuka Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yerun Chen 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 Teruhiko Ishikawa Department of Science Education, Graduate School of Education, Okayama University Hiroyuki Sakagami Department of Anatomy, Kitasato University School of Medicine Futoshi Suizu Clinical Examination Department, Kagawa Prefectural University of Health Sciences Hiroshi Tokumitsu Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ca2+/CaM-dependent protein kinase kinase (CaMKK) phosphorylates and activates downstream kinases, including CaMKI, CaMKIV, PKB, and AMPK, regulating various cellular functions such as neuronal morphogenesis, metabolic control, and pathophysiological pathways, such as cancer progression. CaMKKα/1 is tightly regulated by an autoinhibitory mechanism. CaMKKβ/2 activity is highly Ca2+/CaM-independent (autonomous activity) in vitro and Ca2+/CaM-dependent in cultured cells. Whether these two activity states of CaMKKβ/2 exist in vivo and the detailed regulatory mechanisms for the transition of both activity states remain unclear due to the difficulty in distinguishing the two activity states. In this study, we detected Ca2+-dependent and autonomous CaMKK activity in HeLa cells and successfully separated both activity states of CaMKKβ/2 in mouse brain and testis extracts using a recently developed CaMKK inhibitor (TIM-063)-coupled sepharose, which binds to the catalytic domain in the active state but not in the autoinhibited state. Furthermore, lambda protein phosphatase treatment converted the Ca2+/CaM-dependent form to the autonomous form of CaMKKβ/2, which was not affected by Ala mutation of Ser128, Ser132, and Ser136. The two activity forms of CaMKKβ/2 had equivalent Ca2+/CaM-binding ability. The findings demonstrate the presence of autonomous and Ca2+/CaM-dependent forms of CaMKKβ/2 independently in mouse tissues and cultured cells. The transition of these states of CaMKKβ/2 may be dynamically regulated by the phosphorylation/dephosphorylation of serine residues in the N-terminal regulatory domain. No potential conflict of interest relevant to this article was reported.

Laser Institute of America Acta Medica Okayama 1042-346X 37 1 2025 High-quality welding of copper and aluminum by angled laser irradiation and insert metals 012041 EN Yasuhiro Okamoto Faculty of Environmental, Life, Natural Science and Technology, Okayama University Yuki Yamada Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Akira Okada Faculty of Environmental, Life, Natural Science and Technology, Okayama University Masaki Miyake Kataoka Corporation Takeshi Yamamura Kataoka Corporation Katsutoshi Nagasaki Kataoka Corporation Norio Nishi Kataoka Corporation Copper is an important material in order to use electricity effectively, and aluminum is also an attractive material to perform lightweight construction. Laser welding of copper and aluminum is required, and there are some reports to weld copper and aluminum firmly by laser irradiation from the aluminum side. On the other hand, laser irradiation from the copper side requires high power density to generate a keyhole, which causes the strong convection of molten aluminum into copper. Thus, brittle intermetallic compounds with rich aluminum result in the deterioration of joining strength. Angled laser irradiation enables mild heat input to the aluminum side, and the combination of angled and superposed irradiation of blue and near-infrared (NIR) lasers achieved a remarkable increase of breaking strength. However, the breaking strength is still lower than the base materials. Therefore, insert materials between copper and aluminum plates were investigated by the angled irradiation of blue and NIR lasers from the copper side. The breaking strength with insert materials showed higher values in the order of titanium mesh, nickel foil, and nickel mesh, and its value with the nickel mesh was close to the tensile strength of aluminum in a cross tensile test. Further improvement of breaking strength is possible by inserting the nickel mesh between copper and aluminum plates in the case of angled irradiation of blue and NIR lasers even from the copper side. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 0007-8506 74 1 2025 Improvement of anodic oxide film characteristics of Al-Cu alloy by refinement of IMCs with large-area electron beam irradiation 263 267 EN T. Shinonaga Faculty of Environmental, Life, Natural Science & Technology, Okayama University A. Sebe Graduate School of Environmental, Life, Natural Science & Technology, Okayama University M. Taniguchi Shimano Research Laboratories, R&D Strategy Dept., SHIMANO INC. T. Fujii Shimano Research Laboratories, R&D Strategy Dept., SHIMANO INC. A. Okada Faculty of Environmental, Life, Natural Science & Technology, Okayama University Al-Cu alloy has been widely applied to automobile products due to its light weight and high strength, but pitting corrosion easily occurs due to intermetallic compounds (IMCs) in Al-Cu alloy. Anodizing process has been conventionally performed to improve the corrosion resistance of Al-Cu alloy surface. However, IMCs in Al-Cu alloy lead to defects in anodic oxide film. In this study, refinement of IMCs in Al-Cu alloy surface by large-area EB irradiation was proposed. Experimental results show that reflectance and corrosion resistance of anodic oxide film formed on Al-Cu alloy surface are improved by refinement of IMCs with the EB irradiation. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0378-4371 684 2026 Longitudinal-field fidelity susceptibility analysis of the 𝐽1-𝐽2 transverse-field Ising model around 𝐽2∕𝐽1 ≈ 0.5 131245 EN Yoshihiro Nishiyama Department of Physics, Faculty of Science, Okayama University The square-lattice 𝐽1-𝐽2 transverse-field (TF) Ising model was investigated with the exact diagonalization (ED) method. In order to analyze the TF-driven phase transition, we applied the longitudinal-field fidelity susceptibility 𝜒(ℎ)𝐹, which is readily evaluated via the ED scheme. Here, the longitudinal field couples with the absolute value of the magnetic moment |𝑀| rather than the raw 𝑀 so that the remedied fidelity susceptibility exhibits a peak around the critical point; note that the spontaneous magnetization does not appear for the finite-size systems. As a preliminary survey, the modified fidelity susceptibility 𝜒(ℎ)𝐹 is applied to the analysis of criticality for 𝐽2 = 0, where a number of preceding results are available. Thereby, properly scaling the distance from the multi-criticality, 𝜂 = 0.5−𝐽2, the 𝜒(ℎ)𝐹 data were cast into the crossover-scaling formula, and the multi-critical exponent for 𝜒(ℎ)𝐹 is estimated. The result is cross-checked by the numerically evaluated 𝛽-function behavior. No potential conflict of interest relevant to this article was reported.

Ceramic Society of Japan Acta Medica Okayama 1348-6535 134 1 2026 Structure and acid resistance of fluoride-treated hydroxyapatite particles 31 37 EN Satoshi Hayakawa Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kazuki Ando Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tomohiko Yoshioka Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Topical fluoride is used in clinical dentistry to prevent dental caries. The primary reaction product formed on the tooth surface after topical fluoride application is calcium fluoride (CaF2). In this study, we investigated the effect of deposited CaF2 on the acid resistance of fluoride-treated hydroxyapatite (HAp). Commercial HAp particles were treated with two types of fluoride-containing acetic acid-sodium acetate (Ac-AcNa) buffer solutions, with and without the addition of phosphate ions. X-ray diffraction (XRD) and nuclear magnetic resonance (NMR) analyses confirmed the formation of fluorine-substituted hydroxyapatite (F-HAp), along with a hydration layer containing calcium phosphate and CaF2. Phase composition analysis revealed that the presence of phosphate ions in the fluoride treatment solution reduced the amount of CaF2 deposited. Acid resistance evaluation and phase composition analysis indicated that the initial dissolution rate of the fluoride-treated HAp in Ac-AcNa buffer solutions decreased on surfaces densely covered with CaF2 particles. No potential conflict of interest relevant to this article was reported.

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

International Institute of Anticancer Research Acta Medica Okayama 0250-7005 46 1 2025 P53-Armed Oncolytic Virotherapy Promotes the Efficacy of PD1 Blockade in Murine Osteosarcoma Tumors 69 84 EN MIHO KURE Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences HIROSHI TAZAWA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences KOJI DEMIYA Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences HIROYA KONDO Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences YUSUKE MOCHIZUKI Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TADASHI KOMATSUBARA 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 KOJI UOTANI Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences JOE HASEI 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 YASUO URATA 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 TOSHIFUMI OZAKI Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TOSHIYOSHI FUJIWARA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Aim: Osteosarcoma (OS) is refractory to immune checkpoint inhibitors targeting programmed cell death 1 (PD1)/PD ligand 1 (PD-L1) due to poor immune response. We previously developed telomerase-specific, replication-competent oncolytic adenoviruses non-armed OBP-301 and P53-armed OBP-702 that exert antitumor efficacy against human OS cells. Recently, we demonstrated that P53-armed OBP-702 induces more profound immunogenic cell death and antitumor immune response against human and murine OS cells than does non-armed OBP-301. In the present study, we assessed the combined efficacy of PD1 blockade and P53-armed OBP-702 against murine OS cells.<br> Materials and Methods: Three murine OS cell lines (K7M2, NHOS, NHOS-LM4) were used to assess the cytopathic effect of non-armed OBP-301 and P53-armed OBP-702 by XTT assay. Virus-induced immunogenic cell death was assessed by analyzing the levels of extracellular adenosine triphosphate and high-mobility group box protein B1. The expression of PD-L1 and PD-L2 was analyzed by flow cytometry. The malignant potential of NHOS-LM4 cells was analyzed by a migration and invasion assay. An orthotopic NHOS-LM4 tumor model was used to evaluate the antitumor efficacy of combination therapy with P53-armed OBP-702 and anti-PD1.<br> Results: P53-armed OBP-702 exhibited antitumor potential for the induction of immunogenic cell death, apoptosis, autophagy, and PD-L1/2 upregulation in K7M2 and NHOS cells. NHOS-LM4 cells showed increased migratory and invasive ability compared to NHOS cells. P53-armed OBP-702 significantly suppressed the malignant potential of NHOS-LM4 cells. Combination dosing showed that P53-armed OBP-702 significantly promoted the antitumor effect of PD1 blockade against NHOS-LM4 tumors.<br> Conclusion: Our results suggest that P53-armed OBP-702 is a promising agent for improving the antitumor effect of PD1 blockade in treating invasive OS. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 0718-9508 2025 Suppression of Na+ Uptake Via Apoplastic Flow by Chitosan in Rice EN Maoxiang Zhao Graduate School of Environmental and Life Science, Okayama University Md. Asadulla Al Galib 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 Yoshihiko Hirai Graduate School of Environmental and Life Science, Okayama University Yoshitaka Nakashima Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Izumi C. Mori Institute of Plant Science and Resources, Okayama University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Purpose: Chitosan enhances tolerance to salinity in rice. Apoplastic flow plays a crucial role in the accumulation of sodium (Na+) in rice under salinity. This study investigated the effects of exogenous chitosan on apoplastic flow and Na+ uptake in NaCl-treated rice seedlings. Methods: We employed an apoplastic tracer, trisodium salt of 8-hydroxy-1,3,6-pyrenetrisulphonic acid (PTS), in order to evaluate apoplastic flow in rice (Oryza sativa L., cv. Nipponbare) seedlings that were hydroponically grown in the solution containing NaCl (0 and 25 mM), and chitosan (0 mg L− 1, 10 mg L− 1, and 50 mg L− 1). Results: Application of 25 mM NaCl significantly increased PTS uptake and Na+ content in shoots but did not affect K+ content, resulting in a lower K+/Na+ ratio although 25 mM NaCl did not affect the seedling growth. The application of chitosan suppressed Na+-enhanced PTS uptake and Na+ accumulation in shoots without affecting the K+ content, which led to a higher K+/Na+ ratio. Moreover, chitosan did not affect the reducing sugar content or electrical conductivity in the solution containing NaCl. Conclusions: These results suggest that application of chitosan suppressed Na+-enhanced apoplastic flow to reduce Na+ uptake in rice seedlings. No potential conflict of interest relevant to this article was reported.

Institution of Engineering and Technology (IET) Acta Medica Okayama 1751-9659 19 1 2025 Subspace-Guided Feature Reconstruction for Unsupervised Anomaly Localization e70157 EN Katsuya Hotta Iwate University Chao Zhang University of Toyama Yoshihiro Hagihara Iwate University Takuya Akashi Okayama University Unsupervised anomaly localization aims to identify anomalous regions that deviate from normal sample patterns. Most recent methods perform feature matching or reconstruction for the target sample with pre-trained deep neural networks. However, they still struggle to address challenging anomalies because the deep embeddings stored in the memory bank can be less powerful and informative. Specifically, prior methods often overly rely on the finite resources stored in the memory bank, which leads to low robustness to unseen targets. In this paper, we propose a novel subspace-guided feature reconstruction framework to pursue adaptive feature approximation for anomaly localization. It first learns to construct low-dimensional subspaces from the given nominal samples, and then learns to reconstruct the given deep target embedding by linearly combining the subspace basis vectors using the self-expressive model. Our core is that, despite the limited resources in the memory bank, the out-of-bank features can be alternatively “mimicked” to adaptively model the target. Moreover, we propose a sampling method that leverages the sparsity of subspaces and allows the feature reconstruction to depend only on a small resource subset, contributing to less memory overhead. Extensive experiments on three benchmark datasets demonstrate that our approach generally achieves state-of-the-art anomaly localization performance. No potential conflict of interest relevant to this article was reported.

eLife Sciences Publications, Ltd Acta Medica Okayama 2050-084X 13 2025 Redistribution of fragmented mitochondria ensures symmetric organelle partitioning and faithful chromosome segregation in mitotic mouse zygotes RP99936 EN Haruna Gekko Department of Animal Science, Graduate School of Environment and Life Science, Okayama University Ruri Nomura Department of Animal Science, Graduate School of Environment and Life Science, Okayama University Daiki Kuzuhara Reproductive Centre, Mio Fertility Clinic Masato Kaneyasu Department of Animal Science, Graduate School of Environment and Life Science, Okayama University Genpei Koseki Department of Animal Science, Graduate School of Environment and Life Science, Okayama University Deepak Adhikari Development and Stem Cell Program and Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University Yasuyuki Mio Reproductive Centre, Mio Fertility Clinic John Carroll Development and Stem Cell Program and Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University Tomohiro Kono Department of Bioscience, Tokyo University of Agriculture Hiroaki Funahashi Department of Animal Science, Graduate School of Environment and Life Science, Okayama University Takuya Wakai Department of Animal Science, Graduate School of Environment and Life Science, Okayama University In cleavage-stage embryos, preexisting organelles partition evenly into daughter blastomeres without significant cell growth after symmetric cell division. The presence of mitochondrial DNA within mitochondria and its restricted replication during preimplantation development makes their inheritance particularly important. While chromosomes are precisely segregated by the mitotic spindle, the mechanisms controlling mitochondrial partitioning remain poorly understood. In this study, we investigate the mechanism by which Dynamin-related protein 1 (Drp1) controls the mitochondrial redistribution and partitioning during embryonic cleavage. Depletion of Drp1 in mouse zygotes causes marked mitochondrial aggregation, and the majority of embryos arrest at the 2 cell stage. Clumped mitochondria are located in the center of mitotic Drp1-depleted zygotes with less uniform distribution, thereby preventing their symmetric partitioning. Asymmetric mitochondrial inheritance is accompanied by functionally inequivalent blastomeres with biased ATP and endoplasmic reticulum Ca2+ levels. We also find that marked mitochondrial centration in Drp1-depleted zygotes prevents the assembly of parental chromosomes, resulting in chromosome segregation defects and binucleation. Thus, mitochondrial fragmentation mediated by Drp1 ensures proper organelle positioning and partitioning into functional daughters during the first embryonic cleavage. No potential conflict of interest relevant to this article was reported.