Kazakhstan Society of Geneticists and Breeders Acta Medica Okayama 3134-6359 1 3 2026 Advances and Future Perspectives of Targeted Mutagenesis in Barley 202615 EN Hiroshi Hisano Institute of Plant Science and Resources, Okayama University Targeted mutagenesis technologies, commonly referred to as “genome editing”, have rapidly become transformative tools in crop breeding. Modern crop production faces mounting challenges such as climate change, emerging diseases, and shifting quality demands, creating an urgent need for breeding approaches that enable more precise genetic improvement within shorter timeframes. Targeted mutagenesis capable of introducing mutations accurately and efficiently began with the development of meganucleases and subsequently evolved through ZFNs, TALENs, and CRISPR/Cas systems. Recent technological advances, including multiplex editing and DNA-free genome editing, have made direct modification of elite cultivars increasingly feasible, helping to overcome long-standing barriers associated with genotype dependency and the complexity of polyploid genomes. Targeted mutagenesis has now been applied to a wide range of breeding targets, including disease resistance, tolerance to abiotic stresses, yield-related traits, and quality traits. Moreover, machine learning and AI are beginning to support target selection and phenotype prediction, ushering in an era in which genome editing can be integrated into breeding programs more rationally and efficiently. These scientific developments coincide with regulatory shifts in many countries toward easing restrictions on new genomic techniques (NGTs), particularly by treating SDN-1 genome-edited crops equivalently to those produced through conventional breeding. Such changes are expected to accelerate field trials, commercialization, and international collaboration. Nevertheless, several challenges remain, including bottlenecks in transformation efficiency, off-target assessment, the control of complex traits, societal acceptance, and unresolved regulatory details. Even so, genome editing is poised to become a central technology in next-generation cereal breeding, enabling the development of cultivars with greater resilience, productivity, and adaptability to diverse industrial needs. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2227-9032 14 20 2026 Cross-Cultural Adaptation and Initial Psychometric Evaluation of the Japanese Version of the Chronic Kidney Disease Self-Efficacy Scale (CKDSE-J) 3393 EN Tingting Geng Doctor’s Program, Graduate School of Health Sciences, Okayama University Yuki Kajiwara Faculty of Health Sciences, Okayama University Michiko Morimoto Faculty of Health Sciences, Okayama University Background/Objectives: Self-efficacy is an important determinant of self-care among adults with chronic kidney disease (CKD). The Chronic Kidney Disease Self-Efficacy Scale (CKD-SE) is a disease-specific measure, but its use has not been reported in Japan. This study translated and culturally adapted the CKD-SE into Japanese and conducted an initial psychometric evaluation. Methods: A cross-sectional survey was conducted among Japanese adults with CKD stages G3a–G5 not receiving dialysis. Structural validity and internal consistency were evaluated in 227 participants, and construct validity was evaluated in 222. Structural validity was examined using confirmatory factor analysis (CFA) and exploratory structural equation modeling (ESEM). Results: The original 25-item four-factor CFA showed a poor fit, and ESEM yielded an improper solution involving Item 19. Sequential evaluation resulted in a 23-item structure. The 23-item CFA showed mixed fit, whereas Target ESEM showed improved overall fit (CFI = 0.935, TLI = 0.902, RMSEA = 0.060, SRMR = 0.033). However, several autonomy items showed weak target loadings and cross-loadings. Proposed subscale scores correlated positively with self-care behavior (r = 0.27–0.46), and McDonald’s omega ranged from 0.84 to 0.90. Conclusions: The 23-item CKDSE-J showed improved overall model fit under Target ESEM, but the structural definition of autonomy remained uncertain. Because the structure was refined and evaluated in the same sample, independent replication and further psychometric evaluation are needed. No potential conflict of interest relevant to this article was reported.

IOP Publishing Acta Medica Okayama 0021-4922 65 7 2026 Study of preload mechanism for small piezoelectric transducers with hollow structure for cryogenic environments 07SP13 EN Souta Mimura Graduate School of Environment, Life, Natural Science and Technology, Okayama University Takefumi Kanda Graduate School of Environment, Life, Natural Science and Technology, Okayama University Daisuke Yamaguchi Graduate School of Environment, Life, Natural Science and Technology, Okayama University Kazuki Kubo Graduate School of Environment, Life, Natural Science and Technology, Okayama University Shuichi Wakimoto Graduate School of Environment, Life, Natural Science and Technology, Okayama University In various industrial fields, cryogenic fluids such as liquid hydrogen and liquid nitrogen are increasingly used as fuels and refrigerants. To control the flow rate of those fluids, valves that can be operated in cryogenic environments are needed. In general, the miniaturization of the valve can be achieved by using a piezoelectric ceramic as an actuator to drive the mechanism. Additionally, the properties degradation can be suppressed by applying a preload to the piezoelectric ceramic. To miniaturize the piezoelectric actuator applying preload at low temperature conditions, we use differences in thermal expansion coefficients to apply preload to the piezoelectric ceramics. In this study, we have designed and fabricated a small piezoelectric transducer with a hollow structure for cryogenic environments by using this proposed structure. To evaluate the fabricated transducer, we have measured vibration velocity and estimated the acceleration in cryogenic environments. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0289-0771 2026 Temporally structured plasticity in death-feigning behavior in response to nutritional conditions in Tribolium castaneum EN Kohjiro Shibuya Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kentarou Matsumura Department of General Systems Studies, Graduate School of Arts and Sciences, The University of Tokyo Takahisa Miyatake Faculty of Environmental, Life, Natural Science and Technology, Okayama University Investment in antipredator behavior and foraging both directly influence fitness, yet these investments are often subject to trade-offs. In income-breeding species, individuals may initially prioritize foraging after adult emergence and subsequently increase investment in antipredator behavior as their nutritional condition improves. In this study, we investigated temporal changes in death-feigning behavior, an antipredator response, in the red flour beetle Tribolium castaneum from immediately after adult emergence. Both fed and starved individuals exhibited an increase in death-feigning duration with time after emergence. However, in starved individuals, this trend reversed after approximately 15 days, with a marked decline in duration. These results suggest that the increase in investment in death-feigning behavior early in adulthood is relatively inflexible, whereas behavioral responses become highly plastic in response to environmental conditions around day 15. Furthermore, individuals that were fed until day 18 before starvation showed a less pronounced behavioral change than those subjected to starvation from the beginning of the experimental period, suggesting that the timing of environmental exposure may influence subsequent behavioral responses. Together, these findings suggest that behavioral plasticity is not constant over time but is instead structured across developmental stages. We propose a novel conceptual framework, termed temporally structured plasticity (TSP), to describe this pattern. 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 Cinnamyl alcohol dehydrogenase (CAD) underlies the orange lemma trait and lignin reduction in barley 30805 EN Kazuhiro Sato Institute of Plant Science and Resources, Okayama University Maho Morita Institute of Plant Science and Resources, Okayama University Nami Yamaji Institute of Plant Science and Resources, Okayama University Rinka Kako Graduate School of Agricultural Science, Setsunan University Tomokazu Ushijima Graduate School of Agricultural Science, Setsunan University Hiroshi Hisano Institute of Plant Science and Resources, Okayama University Barley (Hordeum vulgare L.) is one of the world’s major cereal crops and is widely used for feed, brewing, and food. Reducing lignin content in barley grain and straw is beneficial for improving forage digestibility and enhancing the efficiency of bioethanol production. The orange lemma mutation―characterized by orange pigmentation of husks and nodes―has long been associated with altered lignin metabolism; however, its genetic basis has remained unclear. We show that Cinnamyl Alcohol Dehydrogenase (CAD) is the causal gene underlying the orange lemma phenotype in barley. Genetic mapping using a ‘Haruna Nijo’ × ‘L053’ F₂ population and the Barley 50 K SNP array defined a candidate region on chromosome 6H containing the CAD gene. Sequence analysis revealed that all orange lemma mutants, including both naturally occurring and EMS-induced lines, carried nucleotide changes in the CAD gene, resulting in amino acid substitutions or premature stop codons. Furthermore, CRISPR/Cas9-mediated knockout of CAD in the cultivar ‘Golden Promise’ reproduced the orange lemma phenotype, providing functional validation. The knockout plants also showed significantly lower lignin content than wild-type plants. These findings resolve a long-standing question regarding the genetic basis of the orange lemma trait and demonstrate that disruption of CAD alters lignin accumulation in barley. This work provides a valuable genetic resource for breeding barley cultivars with improved biomass utilization for feed and bioenergy applications. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 3 2026 Bioinformatic Prediction of Activation States in Molecular Network Pathways of Eukaryotic Initiation Factor 2 (EIF2) Signaling and Coronavirus Pathogenesis 1525 EN Shihori Tanabe Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences Sabina Quader Innovation Centre of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion Ryuichi Ono Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences Hiroyoshi Y. Tanaka Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Horacio Cabral Department of Bioengineering, Graduate School of Engineering, The University of Tokyo Eukaryotic initiation factor 2 (EIF2) signaling plays a crucial role in regulating mRNA translation and initiating eukaryotic protein synthesis. Computational molecular network pathway analysis of the canonical pathways of the coronaviral infection revealed that EIF2 signaling is inactivated when the coronavirus pathogenesis pathway is activated and vice versa. Our computational analyses indicated that the coronavirus pathogenesis pathway and EIF2 signaling had inverse activation states. Computational investigation of upstream or downstream microRNA (miRNA) revealed that EIF2 signaling directly interacted with miRNAs, including let-7, miR-1292-3p (miRNAs with the seed CGCGCCC), miR-15, miR-34, miR-378, miR-493, miR-497, miR-7, miR-8, and MIRLET7. A total of 36 nodes, including 8 molecules (ATF4, BCL2, CCND1, DDIT3, EIF2A, EIF2AK3, EIF4E, and ERK1/2), 1 complex (the ribosomal 40s subunit), and 1 function (apoptosis) in the coronavirus pathogenesis pathway, overlapped with EIF2 signaling. Alterations in EIF2 signaling may play a role in the pathogenesis of coronavirus. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0289-0771 2026 Experimental evolution of female mating responses to infertile males in Tribolium castaneum EN Yui Fujii Faculty of Environmental, Natural Science and Technology, Okayama University Yui Asano Faculty of Environmental, Natural Science and Technology, Okayama University Kenta Kori Faculty of Environmental, Natural Science and Technology, Okayama University Kentarou Matsumura Graduate School of Arts and Sciences, The University of Tokyo Yukio Yasui Faculty of Agriculture, Kagawa University Chihiro Himuro Okinawa Prefectural Plant Protection Center Yutaka Nakamoto Okinawa Prefectural Plant Protection Center Yoshitaka Sokei Okinawa Prefectural Plant Protection Center Takahisa Miyatake Faculty of Environmental, Natural Science and Technology, Okayama University In many animal populations, infertile males―those unable to reproduce―are commonly present. If females mate exclusively with such males, they fail to produce offspring. How, then, do females deal with this situation? Distinguishing infertile from fertile males both before and after copulation is difficult for females. Here, we tested the hypothesis of bet-hedging polyandry, in which females mitigate the risk of reproductive failure by mating with multiple males, using experimental evolution in the red flour beetle (Tribolium castaneum). Females were cohabited with males artificially sterilized by sublethal radiation and with untreated males at a 1:1 ratio (sterile:untreated). After more than 15 generations, females from the treatment strains did not avoid mating with infertile males, leading to reduced reproductive success. However, compared with the control strains, females from the treated strains tended to mate with a greater number of males. The results raise the possibility that increased polyandry (mating with multiple males) may evolve rather than relying on pre- or post-copulatory discrimination to mitigate the risk posed by infertile males. Bet-hedging is a strategy that spreads or minimizes risk under uncertainty, and these results are consistent with the hypothesis that polyandry can function as a bet-hedging strategy against uncertain male fertility. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0340-5443 80 11 2026 No evidence for differential allocation or sex ratio adjustment in response to male attractiveness in the broad-horned flour beetle 132 EN Kensuke Okada Faculty of Environmental, Life, Natural Science and Technology, Okayama University Katsuya Kiyose Seibukasei Co., Ltd Masako Katsuki Graduate School of Bioagricultural Sciences, Nagoya University Sexual selection theory predicts that females can enhance the benefits of mate choice by increasing reproductive investment (differential allocation) or by biasing offspring sex ratios toward sons (sex ratio adjustment) when mating with attractive males. Clear empirical support for these hypotheses has been documented in many vertebrate taxa, whereas relatively few studies have tested them in invertebrates. Here, we investigated whether females adjust reproductive investment and offspring sex ratio in response to male attractiveness in the beetle Gnatocerus cornutus. We assessed male attractiveness using copulation latency and examined its associations with female lifetime reproductive success, egg size, and offspring sex ratio under single-mating conditions. Our results, however, provide no support for either the differential allocation or sex ratio adjustment hypotheses: females did not alter reproductive investment or offspring sex ratio according to mate quality. In this species, male sexual phenotypes are strongly influenced by environmental conditions. Such phenotype–genotype mismatches may reduce the reliability of male traits as indicators of genetic quality and increase the likelihood of assessment errors by females. This may explain the absence of maternal allocation in relation to mate attractiveness in G. cornutus. Instead, previous work on this beetle indicates that females can secure genetic benefits by remating with more attractive males and biasing fertilization toward their sperm. Our findings therefore suggest that postcopulatory mechanisms, rather than differential maternal allocation, provide a more effective route for females to secure the benefits of mate choice in G. cornutus. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-2607 14 10 2026 Single-Cell Genomics Uncovers an Unexpectedly Abundant, Phylogenetically Hyperdiverse Patescibacteria (Candidate Phyla Radiation) Community in Agricultural Paddy Soil 2213 EN Arslan Ali Institute of Plant Science and Resources, Okayama University Daisuke Saisho Institute of Plant Science and Resources, Okayama University Keiichi Mochida RIKEN Center for Sustainable Resource Science Akio Tani Institute of Plant Science and Resources, Okayama University Patescibacteria, also known as the Candidate Phyla Radiation (CPR), are among the most diverse yet functionally reduced bacterial lineages whose diversity in agricultural soils remains poorly characterized. We applied single-cell genomics to bulk soil from an unfertilized paddy field after rice harvest and drainage. From 384 randomly sorted single cells, 126 medium-to-high-quality SAGs (Single-Amplified Genomes) were recovered, spanning 24 bacterial and archaeal phyla. Unexpectedly, 108 of the 384 SAGs (28.1%) were assigned to Patescibacteria―the most frequently recovered phylum―including 42 of the 126 reliable SAGs. These genomes were notably small (mean 973 kb vs. 1.4–3.2 Mb for other phyla). Because CheckM underestimates completeness in reduced CPR genomes, CheckM2 was applied, raising mean completeness from 59.9% to 83.3% and reclassifying 15 genomes as near-complete (>90%). Phylogenomic analysis using 16 ribosomal protein markers revealed extensive diversity and low average amino acid identity to reference genomes (mean 44.6%), indicating substantial taxonomic novelty. Despite this diversity, functional annotation and OrthoFinder analysis showed a conserved, reduced gene repertoire dominated by translation and DNA repair genes and depleted in amino acid, cofactor, and nucleotide biosynthesis. These results show that modest soil sampling can recover outsized Patescibacteria diversity, underscoring the need for CPR-appropriate completeness assessment. 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 Rapid fluvial response to meter-scale coseismic coastal uplift during the 2024 Noto Peninsula earthquake 742 EN Takayuki Takahashi International Research Institute of Disaster Science, Tohoku University Takuro Ogura Graduate School of Social Sciences, Hitotsubashi University Kotaro Iizuka Center for Spatial Information Science, The University of Tokyo Yoshiya Iwasa Faculty of Education, University of Teacher Education Fukuoka Yuichi S. Hayakawa Center for Spatial Information Science, The University of Tokyo Tatsuto Aoki Institute of Human and Social Sciences, Kanazawa University Nobuhisa Matta Graduate School of Education, Okayama University The response of river profiles to relative base-level change is a key topic in earth surface processes, but observations capturing these changes on unconsolidated deposits at a 1–10 years timescales are scarce. We monitored geomorphic changes at the Hakka River mouth after the 3.5-meter base-level fall caused by coseismic uplift of the 2024 Noto Peninsula earthquake, Japan. Utilizing uncrewed aerial vehicle surveys, we documented a maximum vertical riverbed lowering of 2 m and knickpoint upstream migration of 770-m within the first-year post-earthquake, primarily triggered by erosion during major floods that followed the earthquake. Our findings demonstrate that fluvial terraces can develop within a year or less, following co-seismic coastal uplift. However, the river has not yet reached a renewed graded stage because riverbed armoring resulting from sediment sorting during incision currently inhibits further incision. We suggest that the abandonment of alluvial plains and lowering and widening of the riverbed in the lower 10-km segment will continue over the next decade. No potential conflict of interest relevant to this article was reported.

IEEE Acta Medica Okayama 2026 Tourism Demand Forecasting Using Machine Learning with Cross-Model Feature Ranking 11689307 EN Yomei Hendra Okayama University Tsuyoshi Migita Okayama University Norikazu Takahashi Okayama University This study proposes a machine learning (ML) framework for forecasting tourist visits to a destination, leveraging feature ranking consistency across heterogeneous models. The proposed framework uses a unified stepwise feature selection pipeline to systematically determine a subset of given features that reduces prediction error of an ML model. The transferability of feature rankings is demonstrated through experiments using ML models including Random Forest, XGBoost, LightGBM, and Support Vector Regression (SVR), and a dataset related to tourist visits to West Sumatra, Indonesia. Experimental results show that i) SVR using top four features in the feature ranking based on SHAP achieves the highest accuracy and ii) application of the feature ranking based on XGBoost improves performance stability across other models, reducing error fluctuations. These findings reveal that an optimized feature subset combined with cross-model ranking transfer can outperform more complex ensembles, highlighting the importance of ranking robustness in tourism forecasting. The proposed framework provides a methodological foundation for building interpretable and dataefficient decision support systems for tourism management and policy planning. No potential conflict of interest relevant to this article was reported.

IEEE Acta Medica Okayama 2026 A Novel Iterative Method for Principal Component Analysis 1 6 EN Qiuyun Cao Okayama University Kotaro Hattori Okayama University Tsuyoshi Migita Okayama University Norikazu Takahashi Okayama University Principal Component Analysis (PCA) is a statistical method used for identifying key patterns from a given dataset and reducing its dimensions, while retaining most of the original information. The power method, which is one of the most well-known algorithms for PCA, is simple and easy to implement. However it obtains the specified number of principal components one by one. In this paper, we propose a novel iterative method for PCA, which is expressed as a system of nonlinear difference equations. Unlike the power method, the proposed method can obtain the specified number of principal components in parallel. We also show results of numerical experiments and theoretical analysis to verify the validity of the proposed method. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 3059-3700 2 1 2026 Delta morphology reveals timings of early ocean regression and hydrologic shift on ancient Mars 37 EN Ren Kito Institute for Planetary Materials, Okayama University Hitoshi Hasegawa Faculty of Science and Technology, Kochi University Trishit Ruj Institute for Planetary Materials, Okayama University Tetsuji Muto Department of Environmental Science, Nagasaki University Gian Gabriele Ori International Research School of Planetary Sciences, Università d’Annunzio Goro Komatsu International Research School of Planetary Sciences, Università d’Annunzio Mars’ ancient hydrologic history remains a subject of debate, with competing interpretations suggesting either a large ocean or scattered lacustrine environments. Here, we show that delta morphology on Mars records a shift between these hydrologic regimes. Through controlled tank experiments, we identify two distinct delta types: “lobe-extruding deltas” formed during water-level falls and “stepped fan-deltas” formed during rising water levels. The lobe-extruding deltas occur near proposed paleo-coastlines and are dated to ~3.8–3.2 Ga, consistent with the existence of a Late Noachian–Hesperian ocean and its subsequent regression in the Late Hesperian. In contrast, stepped fan-deltas are found at a wider range of elevations and exhibit significantly younger ages (~2.1–0.1 Ga), suggesting episodic, localized lake formation during the Amazonian. Our findings constrain the timing of the planetary-scale transition from a global hydrosphere to localized aqueous environments and refine the understanding of Mars’ paleoclimate evolution and potential habitability. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0959-8049 248 2026 Molecular characteristics and clinical outcomes of ERBB2-activating mutation-positive non-small cell lung cancer: A Japanese nationwide real-world cohort 117443 EN Masahiro Yamashita Department of Respiratory Medicine, Okayama University Hospital Kiichiro Ninomiya Department of Respiratory Medicine, Okayama University Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Eiji Nakata Center for Comprehensive Genomic Medicine, Okayama University Hospital Ayako Morita Department of Respiratory Medicine, Okayama University Hospital Naofumi Hara Department of Respiratory Medicine, Okayama University Hospital Kenji Takada Department of Respiratory Medicine, Okayama University Hospital Go Makimoto Department of Respiratory Medicine, Okayama University Hospital Toshio Kubo Department of Respiratory Medicine, Okayama University Hospital Eiki Ichihara Department of Respiratory Medicine, Okayama University Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Katsuyuki Hotta Department of Respiratory Medicine, Okayama University Hospital Yosuke Togashi Department of Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Center for Comprehensive Genomic Medicine, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Background: Erb-b2 receptor tyrosine kinase 2 (ERBB2)-activating mutations are well-documented oncogenic drivers in non-small cell lung cancer (NSCLC), occurring in approximately 1–4% of cases. These alterations include a heterogeneous spectrum of variant subtypes; however, the clinicogenomic characteristics and clinical significance of the individual variants have yet to be elucidated.<br> Methods: We searched the nationwide Center for Cancer Genomics and Advanced Therapeutics database, which integrates comprehensive genome profiling data generated in routine clinical practice across Japan, to investigate the molecular landscape and clinical outcomes of patients with ERBB2-mutated NSCLC.<br> Results: A total of 319 patients with ERBB2-activating mutations were included in this retrospective analysis. Although 74% of the patients harbored canonical tyrosine kinase domain (TKD) in-frame insertions, 26% carried noncanonical variants, including TKD missense (8%), transmembrane/juxtamembrane domain (10%), and extracellular domain (ECD) mutations (8%). Co-occurring oncogenic driver alterations were identified in only 18 cases (5.6%) and were largely restricted to noncanonical variants, whereas no co-occurring driver alterations were detected among patients with TKD in-frame mutations. Noncanonical variants―TKD missense and ECD mutations in particular―were associated with an increased tumor mutational burden. Among 288 patients with available survival data, 78 (27%) received trastuzumab deruxtecan (T-DXd) during their clinical course. After excluding patients who had started treatment with T-DXd before undergoing comprehensive genome profiling testing, time-dependent T-DXd exposure was associated with a reduced risk of death (adjusted hazard ratio, 0.63; 95% confidence interval, 0.39–1.01; P = 0.057).<br> Conclusions: ERBB2-mutated NSCLC exhibited substantial molecular heterogeneity, with canonical TKD in-frame insertions characterized by a low frequency of co-occurring oncogenic driver alterations. Among patients harboring ERBB2-activating mutations, exposure to T-DXd was associated with improved overall survival. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1718-7729 33 6 2026 Limited Immune-Mediated Efficacy of Anti-PD-L1/VEGF in EGFR-TKI-Naïve Egfr-Mutant Lung Cancer with Non-Inflamed Tumor Microenvironment 315 EN Atsuko Hirabae Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadahiro Kuribayashi Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Sachi Okawa Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takamasa Nakasuka Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuya Nishii Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Nishimura Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Go Makimoto Department of Respiratory Medicine, Okayama University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Hisao Higo Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kammei Rai Center for Innovative Clinical Medicine, Okayama University Hospital Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Masamichi Sugimoto Product Research Department, Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd. Yosuke Togashi Department of Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Immune checkpoint inhibitors (ICIs) show limited efficacy in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma due to its non-inflamed tumor microenvironment (TME). While quadruple therapy combining chemotherapy, anti-programmed death-ligand 1 (PD-L1), and anti-vascular endothelial growth factor (VEGF) antibodies has shown inconsistent results in EGFR-tyrosine kinase inhibitor (TKI)-pretreated patients, whether anti-VEGF therapy can modulate the intrinsic non-inflamed TME remains unknown. We employed an EGFR-TKI-naïve syngeneic Egfr-mutant mouse model and evaluated effects of anti-VEGF, anti-PD-L1, carboplatin, and paclitaxel as monotherapies and combinations, with TME analysis via immunohistochemistry (IHC), flow cytometry, and RNA sequencing. Anti-PD-L1 showed no antitumor effect, and adding anti-VEGF failed to convert the TME to an inflamed status. Although paclitaxel―but not carboplatin―combined with low-dose anti-VEGF inhibited tumor growth, adding anti-PD-L1 provided no benefit, indicating the anti-VEGF-A antibody evaluated here has a limited role in sensitizing tumors to anti-PD-L1 regardless of chemotherapy. CD8+ T-cell depletion did not attenuate the effect of paclitaxel plus low-dose anti-VEGF, and IHC and RNA sequencing revealed increased natural killer cell infiltration, suggesting a CD8+ T-cell-independent, innate immune mechanism. These findings provide preclinical evidence that the evaluated anti-VEGF has limited immunomodulatory activity in EGFR-TKI-naïve Egfr-mutant tumors with a non-inflamed TME, and suggest immunotherapeutic strategies beyond CD8+ T-cell-mediated immunity warrant investigation. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2026 Clinical Significance of a Cell-Of-Origin-Based Classification in Pancreatic Ductal Adenocarcinoma EN Tatsuya Kikuchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Ako Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hironari Kato Department of Gastroenterology, Okayama City Hospital Hideaki Kinugasa Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaki Uchida Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Oda Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryosuke Hirai Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Terasawa Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Kato Bioinformatics Analysis Center, Kagawa University Tomoyuki Honda Department of Virology, 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 Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with limited therapeutic options and poor clinical outcomes. Although PDAC has traditionally been thought to arise from ductal epithelial cells, recent studies using genetically engineered mouse models have demonstrated that acinar cells can also serve as a cell of origin, giving rise to tumors with distinct biological properties. Here, we investigated whether such lineage-specific differences are preserved in human PDAC. RNA sequencing was performed on resected specimens from 40 treatment-naïve patients with PDAC, and tumors were classified into Acinar- and Ductal-subtypes using lineage-specific gene expression signatures derived from mouse models. This classification strategy was further applied to human PDAC cell lines, followed by in vitro drug sensitivity assays. Patients with Acinar-subtype tumors had significantly longer overall survival than those with Ductal-subtype tumors (median, 54.0 vs. 26.5 months; p < 0.01), and multivariate analysis identified the ductal cell-derived tumor signature as an independent predictor of poor prognosis (HR, 3.74 [95% CI, 1.41–9.97]; p = 0.01). Among patients who developed postoperative recurrence, Acinar-subtype tumors were associated with more durable disease control (≥ 10 months) following gemcitabine-based chemotherapy than Ductal-subtype tumors (63.6% vs. 16.7%; p = 0.02). Consistently, pancreatic cancer cell lines classified as Acinar-subtype showed greater sensitivity to gemcitabine (p < 0.01) and paclitaxel (p < 0.05). These findings extend the clinical relevance of cell-of-origin signatures beyond prognostic stratification, highlighting the potential of cell-of-origin-based classification for treatment stratification and precision medicine in PDAC. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0366-7022 55 9 2026 Size-dependent reflection behavior of graphene oxide-based photonic crystals upag176 EN Daisuke Ogawa Department of Chemistry and Materials, Faculty of Textile Science and Technology, Shinshu University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Koki Sano Department of Chemistry and Materials, Faculty of Textile Science and Technology, Shinshu University Graphene oxide (GO) nanosheets can spontaneously self-assemble into photonic crystals in water, exhibiting structural colors based on Bragg reflection. In this study, we systematically investigated the effect of GO lateral size on the reflection behavior of GO-based photonic crystals. Reflection spectroscopy revealed that both the reflection peak intensity and its time-dependent evolution strongly depended on the GO lateral size, suggesting the existence of an optimal size range for maximizing their reflection intensity. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0931-2250 212 6 2026 Validation and Fine Mapping of Quantitative Trait Loci Associated With Salinity Tolerance at Reproductive Stage on Chromosome 6 in the Rice Variety Nona Bokra e70252 EN M M Emam Ahmed Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koki Maeoka Graduate School of Environment and Life Science, Okayama University Yuki Sakata School of Agriculture, Okayama University Asami Tomita Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshihiko Hirai Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Soil salinity is a major abiotic stress affecting rice production globally. Previously, one promising salinity-tolerant line (SL535) was identified through screening of Nona Bokra-CSSLs with a Koshihikari background. In 2016, 102 F2 individuals derived from SL535/Koshihikari were evaluated under long-term salt stress, with salt treatment imposed from the active tillering stage to maturity to investigate salt tolerance at the reproductive stage. Three QTLs for plant dry weight, panicle number, and panicle weight were detected on chromosome 6. This genomic region was further validated in 2019 and 2020 for plant dry weight, tiller number, and Na+ and Cl− contents using homozygous lines with or without the Nona Bokra allele in a Koshihikari background. As expected, significantly higher tiller number and lower Na+ and Cl− contents were maintained in plants carrying the Nona Bokra allele (NIL) at the full-heading stage. In 2023, seven newly developed NILs were evaluated for agronomic traits under control and salt stress conditions. Based on their performance, the QTL for plant dry weight, qPDW6.1, was narrowed down to a 390 kb region ranging from 4.78 to 5.17 Mb on chromosome 6. Within this region, several stress-related candidate genes were predicted based on annotation information and variant effect prediction analysis. Among them, two genes, Os06g0196700 (Auxin response factor 1) and Os06g0199100 (P-type pentatricopeptide repeat protein), were considered the most likely candidate genes associated with salt tolerance. These findings provide a foundation for future gene cloning and functional validation studies, which may help elucidate the genetic and molecular mechanisms underlying salt tolerance at the reproductive stage. No potential conflict of interest relevant to this article was reported.

IEEE Acta Medica Okayama 2026 Multi-Objective Optimization for Decision Support for Supply Warehouse Location Under Earthquake Disaster Conditions ― A Case Study in Okayama City, Japan ― 684 689 EN Atsushi Kuroda Okayama University Takaki Kawamoto Okayama University In this study, we consider a Nankai Trough earthquake scenario and examine the optimal location of a new emergency supply warehouse to strengthen the emergency supply chain. Conventional facility location studies have primarily emphasized accessibility to demand points. In contrast, this study also incorporates safety based on disaster risk. We formulate an extended p-median model as a multi-objective optimization problem that simultaneously considers accessibility and safety as two evaluation criteria. Multiple scalarization methods are applied to obtain solutions under different preference settings. Numerical experiments using real-world data reveal a clear trade-off between accessibility and safety. The results also show that differences in scalarization methods affect the characteristics of the obtained solutions. Furthermore, by comparing our results with the previous study, we show that the proposed approach can flexibly derive a wide range of solutions, from distance-oriented to safety-oriented configurations. These findings provide useful insights for proposing resilient supply locations in disaster preparedness planning. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 19 2026 Impaired Myostatin Function Alters Body Composition Without Detectable Attenuation of Imiquimod-Induced Psoriasiform Dermatitis 8518 EN Yoshihiro Matsuda Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin Morizane Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuma Sakamoto Department of Immunology and Molecular Genetics, Kawasaki Medical School Nobuyasu Baba Department of Immunology and Molecular Genetics, Kawasaki Medical School Masanori Iseki Department of Immunology and Molecular Genetics, Kawasaki Medical School Daiki Takezaki Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshio Kawakami Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin-Ichiro Nishimatsu Department of Natural Sciences, Kawasaki Medical School Yutaka Ohsawa Department of Neurology, Kawasaki Medical School Yoshihide Sunada Department of Neurology, Kawasaki Medical School Tomoyuki Mukai Department of Immunology and Molecular Genetics, Kawasaki Medical School Psoriasis is a chronic inflammatory skin disease closely associated with obesity and metabolic dysfunction. While excess adiposity is considered a key risk factor, the independent contribution of body composition to psoriatic inflammation remains unclear. Myostatin negatively regulates skeletal muscle growth, and its inhibition leads to muscle hypertrophy and reduced adiposity. In this study, we investigated whether altered body composition due to impaired myostatin function affects imiquimod (IMQ)-induced psoriasiform dermatitis. Wild-type (WT) and dominant-negative myostatin transgenic mice were fed either a normal diet or a high-fat diet (HFD) for 10 weeks, followed by topical IMQ treatment to induce dermatitis. Mutant mice exhibited increased skeletal muscle mass and reduced visceral fat compared with WT controls, indicating marked changes in body composition. In WT mice, HFD feeding increased fat mass and tended to aggravate IMQ-induced ear swelling. In contrast, no significant effect of impaired myostatin function on ear thickness, epidermal hyperplasia, or the expression of psoriasis-associated genes was detected, despite reduced visceral fat. Under the present experimental conditions, these changes in body composition were not associated with a detectable attenuation of psoriasiform skin inflammation. Our results suggest that obesity-related psoriasis is influenced by metabolic and immunological factors beyond body composition. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1465-3621 2026 Early progression after immune checkpoint inhibitor therapy in recurrent or metastatic head and neck squamous cell carcinoma: association with disease distribution in a single-center retrospective study hyag167 EN Hiroki Noda Department of Otolaryngology―Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuma Makino Department of Otolaryngology―Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuto Naoi Department of Otolaryngology―Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Fujimoto Department of Otolaryngology―Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology―Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Immune checkpoint inhibitors (ICIs) are an important treatment option for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, some patients experience rapid disease progression shortly after ICI initiation, potentially resulting in deterioration of general condition and limited opportunities for subsequent treatment. This study investigated clinicopathological factors associated with early progression after ICI initiation in patients with R/M HNSCC.<br> Methods: We retrospectively analyzed 207 patients with R/M HNSCC treated with nivolumab or pembrolizumab at a single institution. Early progression was defined as disease progression within 90 days after ICI initiation. Associations between clinicopathological factors and early progression were evaluated using logistic regression analyses.<br> Results: Early progression was observed in 80 patients (38.6%). In an exploratory survival comparison, patients with early progression had significantly shorter overall survival than those without early progression. Early progression rates increased from distant-only disease to locoregional-only disease and combined locoregional and distant disease. In multivariable analysis, combined locoregional, and distant disease showed the strongest independent association with early progression. Elevated neutrophil-to-lymphocyte ratio and hypoalbuminemia were also independently associated with early progression. In contrast, treatment regimen, treatment line, number of lesions, and bulky disease were not significantly associated with early progression.<br> Conclusion: Disease distribution was associated with early progression after ICI initiation in patients with R/M HNSCC, with combined locoregional and distant disease showing the strongest independent association. These findings suggest that both disease status and host condition may influence failure to achieve adequate disease control shortly after ICI initiation. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2475-0328 2026 The Geriatric Nutritional Risk Index Predicts Short‐ and Long‐Term Outcomes in the Oldest‐Old With Colorectal Cancer: A Multi‐Institutional Analysis of 225 Nonagenarians EN Toshiaki Toshima Department of Surgery, Kagawa Rosai Hospital Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Hospital Satoe Takanaga Department of Gastroenterological Surgery, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Ryo Inada Department of Surgery, Kochi Health Sciences Center 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 Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Hospital Tatsuo Matsuda Department of Surgery, Matsuda Hospital Tatsuo Umeoka Department of Surgery, Matsuyama City Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Hospital The Setouchi Colorectal Neoplasm Registration Study Group Aim: Surgical outcomes for colorectal cancer (CRC) in nonagenarians remain uncertain due to frailty, comorbidities, and malnutrition. The Geriatric Nutritional Risk Index (GNRI) is associated with surgical outcomes in older patients with CRC, but its prognostic value in nonagenarians is unclear. This study evaluated the GNRI's predictive value for short- and long-term surgical outcomes in this population.<br> Methods: We retrospectively analyzed 225 nonagenarians undergoing surgical resection of CRC at 15 institutions between 2011 and 2022. Patients were stratified by GNRI-high/low status using two cutoffs: 98 (Cohort 1) and 86 (Cohort 2). Outcomes included postoperative complications, length of hospital stay, and overall survival (OS). Stabilized inverse-probability-of-treatment weighting (IPTW) was used to adjust for measured confounding.<br> Results: The median age was 92 years (female, 64.9%; colon cancer, 79.6%). GNRI-high patients had higher body mass index and albumin levels. Complication rates did not differ between the groups. After adjustment, GNRI-high patients in Cohort 1 had a shorter expected hospital stay (ratio 0.70, 95% CI 0.51–0.96; p = 0.025) but no significant OS difference. In Cohort 2, GNRI-high patients had better OS (p < 0.01), confirmed by adjusted Cox models (HR 0.54, 95% CI 0.35–0.82; p < 0.01).<br> Conclusions: Preoperative GNRI was associated with hospital stay and OS in nonagenarians undergoing CRC surgery, although the OS association was significant only with the cohort-derived cutoff of 86, which requires external validation, and not with the literature-based cutoff of 98. The GNRI is a simple tool to stratify surgical risk and optimize perioperative nutritional status in this vulnerable population. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0140-7791 2026 Natural Variation in Brachypodium distachyon Primarily Links Lignin Reinforcement to Rhizoctonia solani Resistance EN Rozi Fernanda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Niranjan Mahadevan Tea Research Institute of Sri Lanka Megumi Watanabe Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nanami Sakata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hidenori Matsui Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuhiro Toyoda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuki Ichinose Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiteru Noutoshi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0300-2896 61 5 2025 Histological Features and Gene Expression Profiling in Lung Transplantation From Donation After Circulatory Death 299 302 EN Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohisa Sakaue Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yujiro Kubo Department of Thoracic Surgery and Lung Transplantation, Hospital Universitario Puerta de Hierro-Majadahonda Tatsuya Hayashi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Elvira Ramil Sequencing and Molecular Biology Unit, Hospital Universitario Puerta de Hierro-Majadahonda Antonio J. Sánchez-López Biobank, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana María Jose Coronado Confocal Microscopy Unit, Hospital Universitario Puerta de Hierro-Majadahonda Lucas Hoyos Department of Thoracic Surgery and Lung Transplantation, Hospital Universitario Puerta de Hierro-Majadahonda Alejandra Romero Department of Thoracic Surgery and Lung Transplantation, Hospital Universitario Puerta de Hierro-Majadahonda Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences David Gomez-de-Antonio Department of Thoracic Surgery and Lung Transplantation, Hospital Universitario Puerta de Hierro-Majadahonda No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1012-2443 94 1 2025 An XAI-based meta-parameter tuning for time-series forecasting 1 18 EN Hiroyuki Nakagawa Okayama University Shimon Sumita Osaka University Ryuichi Iida Okayama University Tatsuhiro Tsuchiya Osaka University How can we efficiently determine meta-parameter values for deep learning-based time-series forecasting given a time-series dataset? This paper introduces Xtune, an efficient and novel meta-parameter tuning method for deep learning-based time-series forecasting, leveraging explainable AI techniques. In particular, this study focuses on optimizing the window size for time-series forecasting. Xtune determines the optimal meta-parameter value for these methods and can also be applied to tune the window size for anomaly detection methods that utilize deep learning-based time-series forecasting. Extensive experiments on real-world datasets and forecasting methods demonstrate that Xtune efficiently identifies the optimal meta-parameter value and consistently outperforms the existing methods in terms of execution speed. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2210-6014 15 1 2025 Relationship Between Heated Tobacco Products and Placental Abruption: A Prospective Cohort Study Using Online Questionnaire 30 EN Hikaru Ooba Center for Innovative Clinical Medicine, Okayama University Hospital Jota Maki Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Tabuchi Division of Epidemiology, School of Public Health, Tohoku University Graduate School of Medicine Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Placental abruption (PA) is a critical obstetric complication, with maternal smoking recognized as a key risk factor. Despite the increased use of heated tobacco products (HTPs), the impact of HTPs remains unclear. This study investigated whether pregnant women using HTPs are at a higher risk of PA than non-users.<br> Methods: We analyzed data from “the Japan COVID-19 and Society Internet Survey,” a prospective, self-reported online survey cohort. Questionnaires were randomly distributed between July 28, 2021, and August 30, 2021. Pregnant respondents in 2021 were invited to complete an additional survey from February 14, 2022, to February 28, 2022. We set the outcome as the absolute risk difference (aRD) and relative risk ratio (rRR) of PA incidence due to smoking HTPs in the first trimester of pregnancy. The sample size included 12 836 participants. We calculated outcomes using a generalized linear model (GLM) and inverse probability of treatment weighting (IPTW). We also performed a Bayesian approach and multiple-bias analysis for sensitivity analysis.<br> Results: We found the robust aRD of 0.07 (95% confidence interval (CI): 0.06, 0.09) and the rRR of 11.3 (95% CI: 7.5, 17.0). Multiple bias analyses showed that unmeasurable confounders would need to have at least an rRR = 14 relationship with both exposure and outcome to disprove the observed association. There has not been post hoc analysis or secondary use of data.<br> Conclusion: Early pregnancy use of HTPs is associated with an increased risk of PA. No potential conflict of interest relevant to this article was reported.

American Astronomical Society Acta Medica Okayama 0004-637X 980 1 2025 Observing Supernova Neutrino Light Curves with Super-Kamiokande. V. Distance Estimation with Neutrinos 117 EN Yudai Suwa Department of Earth Science and Astronomy, The University of Tokyo Akira Harada Interdisciplinary Theoretical and Mathematical Sciences Program (iTHEMS), RIKEN Masamitsu Mori Division of Science, National Astronomical Observatory of Japan Ken’ichiro Nakazato Faculty of Arts and Science, Kyushu University Ryuichiro Akaho Faculty of Science and Engineering, Waseda University Masayuki Harada Department of Physics, Okayama University Yusuke Koshio Department of Physics, Okayama University Fumi Nakanishi Department of Physics, Okayama University Kohsuke Sumiyoshi National Institute of Technology, Numazu College Roger A. Wendell Kavli Institute for the Physics and Mathematics of the Universe (Kavli IPMU, WPI), Todai Institutes for Advanced Study, The University of Tokyo Neutrinos are pivotal signals in multimessenger observations of supernovae (SNe). Recent advancements in the analysis method of supernova (SN) neutrinos, especially in quantitative analysis, have significantly broadened scientific possibilities. This study demonstrates the feasibility of estimating distances to SNe using neutrinos. This estimation utilizes the direct relationship between the radius of a neutron star (NS) and the distance to the supernova, which is analogous to main-sequence fitting. The radius of an NS is determined with an approximate uncertainty of 10% through observations such as X-rays and gravitational waves. By integrating this information, the distance to the supernova can be estimated with an uncertainty of within 15% at a 95% confidence level. It has been established that neutrinos can pinpoint the direction of supernovae, and when combined with distance estimates, three-dimensional localization becomes achievable. This capability is vital for follow-up observations using multimessenger approaches. Moreover, more precise distance determinations to SNe through follow-up observations, such as optical observations, allow for accurate measurements of neutron-star radii. This data, via the neutron-star mass–radius relationship, could provide various insights into nuclear physics. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 1758-8359 17 2025 Clinical impact of hypomagnesemia induced by necitumumab plus cisplatin and gemcitabine treatment in patients with advanced lung squamous cell carcinoma: a subanalysis of the NINJA study 1 16 EN Shigeru Tanzawa Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Hospital Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Yasunori Murata Department of Respiratory Medicine, Ichinomiya Nishi Hospital Masafumi Takeshita Department of Respiratory Medicine, Ichinomiya Nishi Hospital Fumihiko Kinoshita Department of Thoracic Oncology, NHO Kyushu Cancer Center Takatoshi Fujishita Department of Thoracic Oncology, NHO Kyushu Cancer Center Shunichi Sugawara Department of Pulmonary Medicine, Sendai Kousei Hospital Yosuke Kawashima Department of Pulmonary Medicine, Sendai Kousei Hospital Kazuki Hashimoto Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Masahide Mori Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Akihiko Miyanaga Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Anna Hayashi Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Hisashi Tanaka Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine Ryoichi Honda Department of Respiratory Medicine, Asahi General Hospital Masafumi Nojiri Department of Respiratory Medicine, Kanazawa Medical University Yuki Sato Department of Respiratory Medicine, Kobe City Medical Center General Hospital Akito Hata Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center Nobuhisa Ishikawa Department of Respiratory Medicine, Hiroshima Prefectural Hospital Toshiyuki Kozuki Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center Takahisa Kawamura Department of Thoracic Oncology, Osaka International Cancer Institute Go Saito Department of Respirology, Graduate School of Medicine, Chiba University Teppei Yamaguchi Department of Thoracic Oncology, Aichi Cancer Center Hospital Kazuhiro Asada Department of Respiratory Medicine, Shizuoka General Hospital Satoshi Tetsumoto Department of Respiratory Medicine and Clinical Immunology, Suita Municipal Hospital Hiroshi Tanaka Department of Internal Medicine, Niigata Cancer Center Hospital Satoshi Watanabe Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences Yukihiro Umeda Department of Respiratory Medicine, Faculty of Medical Sciences, University of Fukui Kakuhiro Yamaguchi Department of Respiratory Medicine, Hiroshima University Hospital Kazuya Nishii Department of Respiratory Medicine, NHO Iwakuni Clinical Center, Iwakuni, Yamaguchi, Japan Kosuke Tsuruno Department of Respiratory Medicine, Iizuka Hospital Yuki Misumi Department of Respiratory Medicine, Yokohama Municipal Citizen’s Hospital Hiroshi Kuraishi Department of Pulmonary Medicine, Nagano Red Cross Hospital Ken Yoshihara Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine Akira Nakao Department of Respiratory Medicine, Fukuoka University Hospital Akihito Kubo Department of Respiratory Medicine and Allergology, Aichi Medical University Toshihiko Yokoyama Department of Respiratory Medicine, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Kana Watanabe Department of Respiratory Medicine, Miyagi Cancer Center Nobuhiko Seki Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Background: The clinical impact of hypomagnesemia induced by necitumumab plus gemcitabine and cisplatin (GCN) as a second-line or later therapy is unclear.<br> Objective: We aimed to evaluate the clinical characteristics and survival impact of hypomagnesemia induced by this therapy.<br> Design: This was a sub-analysis of the retrospective multicenter NINJA study.<br> Methods: Among the 93 patients enrolled in the NINJA study, this subanalysis included 75 patients with baseline serum magnesium concentrations.<br> Results: The incidence of grade ⩾2 hypomagnesemia was 18.0% in the patients with normal baseline serum magnesium concentrations and 42.8% in those with low concentrations (p = 0.073). The discontinuation rates of GCN treatment owing to hypomagnesemia in each group were 0% and 7.1%, respectively (p = 0.187). The number of necitumumab doses and severity of hypomagnesemia were positively correlated (r = 0.389, p < 0.001). Patients who developed hypomagnesemia in fewer than 21 days after the first dose of GCN (n = 12) had significantly poorer progression-free survival (PFS) than those without the condition (n = 63; median: 4.1 vs 4.4 months, p = 0.048). A similar trend was observed for OS (median: 9.7 vs 15.7 months, p = 0.062). These results were maintained after multivariate analyses (PFS: hazard ratio (HR) 2.46, p = 0.014; OS: HR 2.78, p = 0.021).<br> Conclusion: GCN as a second-line or later therapy may be tolerable regardless of the patient’s baseline serum magnesium concentration. On the other hand, early serum magnesium reduction with this therapy is associated with a poor prognosis. However, caution should be needed because our results lacked sufficient information for confounding variables other than those analyzed here that may influence the correlation between hypomagnesemia and survival. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 1758-8359 17 2025 Skin disorder within 30 days is a favorable prognostic factor in patients with lung squamous cell carcinoma treated with necitumumab plus gemcitabine and cisplatin: a sub-analysis of the NINJA study 1 13 EN Fumihiko Kinoshita Department of Thoracic Oncology, NHO Kyushu Cancer Center Shigeru Tanzawa Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Yasunori Murata Department of Respiratory Medicine, Ichinomiya Nishi Hospital Masafumi Takeshita Department of Respiratory Medicine, Ichinomiya Nishi Hospital Masafumi Yamaguchi Department of Thoracic Oncology, NHO Kyushu Cancer Center Shunichi Sugawara Department of Pulmonary Medicine, Sendai Kousei Hospital Yosuke Kawashima Department of Pulmonary Medicine, Sendai Kousei Hospital Kazuki Hashimoto Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Masahide Mori Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Akihiko Miyanaga Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Anna Hayashi Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Hisashi Tanaka Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine Ryoichi Honda Department of Respiratory Medicine, Asahi General Hospital Masafumi Nojiri Department of Respiratory Medicine, Kanazawa Medical University Yuki Sato Department of Respiratory Medicine, Kobe City Medical Center General Hospital Ken Yamamoto Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center Ken Masuda Department of Respiratory Medicine, Hiroshima Prefectural Hospital Toshiyuki Kozuki Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center Takahisa Kawamura Department of Thoracic Oncology, Osaka International Cancer Institute Takuji Suzuki Department of Respirology, Graduate School of Medicine, Chiba University Teppei Yamaguchi Department of Thoracic Oncology, Aichi Cancer Center Hospital Kazuhiro Asada Department of Respiratory Medicine, Shizuoka General Hospital Satoshi Tetsumoto Department of Respiratory Medicine and Clinical Immunology, Suita Municipal Hospital Hiroshi Tanaka Department of Internal Medicine, Niigata Cancer Center Hospital Satoshi Watanabe Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences Yukihiro Umeda Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui Kakuhiro Yamaguchi Department of Respiratory Medicine, Hiroshima University Hospital Shoichi Kuyama Department of Respiratory medicine, NHO Iwakuni Clinical Center Kosuke Tsuruno Department of Respiratory Medicine, Iizuka Hospital Yuki Misumi Department of Respiratory Medicine, Yokohama Municipal Citizen’s Hospital Hiroshi Kuraishi Department of Respiratory Medicine, Nagano Red Cross Hospital Ken Yoshihara Division of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine Akira Nakao Department of Respiratory Medicine, Fukuoka University Hospital Akihito Kubo Department of Respiratory Medicine and Allergology, Aichi Medical University School of Medicine Toshihiko Yokoyama Department of Respiratory Medicine, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Kana Watanabe Department of Respiratory Medicine, Miyagi Cancer Center Nobuhiko Seki Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Background: Skin disorders are major adverse events associated with necitumumab plus gemcitabine and cisplatin (Neci + GC) administration. However, the prognostic effect of skin disorders in patients with lung squamous cell carcinoma (LSCC) administered Neci + GC is unclear.<br> Objectives: We examined this prognostic effect in patients with LSCC, and the usefulness of minocycline administration.<br> Design: This was a sub-analysis of the retrospective multicenter NINJA study.<br> Methods: We performed a landmark survival analysis according to the presence of skin disorders at Day 30 of treatment and examined the usefulness of minocycline for treating skin disorders.<br> Results: Among the 93 patients, 62 (66.7%) had a skin disorder at Day 30. Nineteen, 30, and 13 patients experienced Grade 1, 2, and 3 skin disorders, respectively. The overall survival (OS) and progression-free survival (PFS) of patients with skin disorders at Day 30 were longer than those of patients without skin disorders (median OS: 434 vs 278 days, p = 0.0201; median PFS: 148 vs 82 days, p = 0.0835). Multivariable analysis showed that a skin disorder at Day 30 was an independent prognostic factor for both OS (p = 0.0044) and PFS (p = 0.0514). Of the 62 patients with skin disorders at Day 30, 38 (61.3%) were taking minocycline, and their time to treatment failure (TTF) was better than that in patients not taking minocycline (median TTF: 148 vs 101 days, p = 0.0495).<br> Conclusion: A skin disorder within 30 days was a favorable prognostic factor for patients with LSCC administered Neci + GC. Additionally, minocycline administration may be beneficial in patients who develop skin disorders within 30 days. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0961-8368 35 10 2026 Conformational stability and domain‐specific structural features of tumor autoantigens regulate autoantibody epitope propensity e70808 EN Ai Miyamoto Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Rika Yamamoto Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ryui Sakaguchi Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Rikako Kutsuma Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takeru Mori Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mirei Masui Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tomoko Honjo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Midori Futami Department of Bioscience, Faculty of Life Science, Okayama University of Science Mariko Morii Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Hiromi Watanabe Department of Respiratory Medicine, Okayama University Hospital Tadahiro Kuribayashi Department of Respiratory Medicine, Okayama University Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Junichiro Futami Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Autoantibodies against tumor-associated autoantigens are clinically valuable biomarkers for cancer diagnosis; however, the structural determinants governing epitope selectivity remain unknown. Here, we investigated whether the intrinsic conformational stability of target autoantigens regulates the epitope propensity of tumor-associated autoantibodies in non-small cell lung cancer. Using a dual-antigen Luminex bead-based assay that presents each autoantigen in both native and S-cationized denatured forms, we directly compared IgG autoantibody reactivity toward conformational and linear epitopes across 11 autoantigens. Intrinsically disordered aggregation-prone autoantigens, including cancer/testis antigens, NY-ESO-1, and XAGE-1b, predominantly elicit linear epitope-directed responses, whereas thermodynamically stable soluble autoantigens generally drive conformational epitope recognition. Intriguingly, for autoantigens harboring both ordered and disordered segments, the immune response is strictly guided by domain-specific biophysics: while p53-specific antibodies preferentially target their flanking disordered regions, the Wilms' tumor protein 1 exceptionally drives conformational recognition directed toward its structured zinc-finger domains. Recombinant solubility in Escherichia coli broadly correlated with epitope class across all 11 autoantigens, confirming that prokaryotic folding efficiency generally reflects intrinsic conformational stability in vivo for autonomously folding monomeric cytosolic proteins. Independent computational validation was provided by the concordance between the experimental solubility ratios and AlphaFold3-derived Rosetta energy unit/solvent-accessible surface area values, demonstrating the convergence of thermodynamic estimates and patient-derived immune data within a unifying biophysical framework. These findings establish that the autoantibody epitope propensity is closely associated with the thermodynamic stability of the target autoantigen and provide a rational basis for tailoring antigen preparation strategies for autoantibody-based cancer diagnosis. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 0094-8276 53 18 2026 Hydrogen-Bond Symmetrization in Hydrous Aluminous Silica Enhances Deep-Mantle Water Cycle e2026GL123823 EN Chaoshuai Zhao State Key Laboratory of Precision Geodesy, University of Science and Technology of China Zhu Mao State Key Laboratory of Precision Geodesy, University of Science and Technology of China Yingxin Yu Department of Earth Sciences, University of Oxford Ningyu Sun State Key Laboratory of Precision Geodesy, University of Science and Technology of China Yunhua Fu SKLab‐DeepMinE, MOEKLab‐OBCE, School of Earth and Space Sciences, Peking University Jianbo Zhang Center for High‐Pressure Science and Technology Advance Research Hanns‐Peter Liermann Deutsches Elektronen‐Synchrotron DESY Renbiao Tao Center for High‐Pressure Science and Technology Advance Research Takayuki Ishii Institute for Planetary Materials, Okayama University (Al, H)-bearing CaCl2-type SiO2 serves as a key water carrier in Earth's deep-water cycle. Evolution of hydrogen-bond symmetrization in this phase was measured up to 62 GPa and 800 K by synchrotron infrared and Raman spectroscopy, and X-ray diffraction. It undergoes symmetrization at ∼30 GPa and 300 K, while elevated temperature to 800 K lowers the onset pressure to ∼12 GPa. This implies that the symmetrized phase will form directly near the base of the transition zone in (Al, H)-rich subducted slabs, and deeper in (Al, H)-poor slabs via transformation from stishovite. More importantly, this symmetrization state stiffens the crystal lattice and immobilizes hydrogen within the structure, enhancing water retention and preventing hydrogen loss during subduction to the lower mantle. Our findings suggest that this phase acts as an important deep-water reservoir capable of transporting water to the lower mantle, thereby linking the deep-water cycle from Earth's surface to core-mantle boundary. No potential conflict of interest relevant to this article was reported.

Microbiology Society Acta Medica Okayama 0022-2615 75 3 2026 Investigation of carbapenem-hydrolysing Klebsiella oxytoca strains lacking detectable carbapenemase genes 002139 EN Hiroshi Teraguchi Department of Clinical Laboratory, Kindai University Nara Hospital Ayaka Oda Dental School, Okayama University Satoyo Wakai Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Sayoko Kawakami Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Koki Yoshida Department of Clinical Laboratory, Kindai University Nara Hospital Wataru Hayashi Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Norikazu Kitamura Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Yo Sugawara Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Naoya Ohara Dental School, Okayama University Motoyuki Sugai Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Koji Yahara Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Aki Hirabayashi Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Introduction. Carbapenemase-producing Enterobacterales (CPE) pose a clinical concern due to limited treatment options and plasmid-mediated spread of carbapenemase genes. The modified carbapenem inactivation method (mCIM) is increasingly used in clinical settings to detect CPE.<br> Gap Statement. Interpretation of mCIM results for isolates with reduced carbapenem susceptibility remains challenging.<br> Aim. To assess the interpretation of positive mCIM results in Klebsiella oxytoca isolates lacking detectable carbapenemase genes and exhibiting reduced carbapenem susceptibility and to propose a phenotypic testing strategy for accurate evaluation.<br> Methodology. Antimicrobial susceptibility testing with clavulanic or dipicolinic acid supplementation, phenotypic carbapenemase assays, carbapenem hydrolysis assays and whole-genome sequencing (WGS) were conducted on K. oxytoca strains.<br> Results. K. oxytoca strains were isolated from both blood and urine samples of a patient in a Japanese hospital. Although classified as susceptible by clinical breakpoints, these isolates exhibited reduced susceptibility to carbapenems. Although these strains were mCIM-positive, the zinc-supplemented carbapenem inactivation method did not support the presence of metallo-β-lactamase (MBL) activity. MIC reductions in the presence of CVA were consistent with inhibition of a class A β-lactamase. In contrast, dipicolinic acid supplementation did not reduce the meropenem MIC, ruling out MBL production. Furthermore, WGS revealed that both K. oxytoca strains lacked known carbapenemase genes, with blaOXY-2-4 being the only identifiable β-lactamase gene encoding a class A enzyme. No novel β-lactamase genes were identified; however, an enhanced blaOXY-2-4 expression-associated point mutation was found in the promoter region. Both K. oxytoca strains exhibited carbapenem-hydrolysing activity, although to a lesser extent than that of the MBL-producing strain.<br> Conclusion. We identified K. oxytoca strains that lacked known carbapenemase genes but that yielded positive mCIM results, possibly due to OXY-2 overproduction. Our study findings emphasize the need for cautious mCIM result interpretation for K. oxytoca and highlight the diagnostic value of combined susceptibility testing with clavulanic and dipicolinic acids to distinguish the underlying resistance mechanisms. Combining complementary clinical laboratory tests will enable clarification of the factors underlying mCIM positivity and guide clinical decision-making. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0032-0781 2026 Disrupted FLOWERING LOCUS C alleles from weedy radish enhance the florigenic potential of rootstocks for graft-mediated floral induction in Brassicaceae pcag119 EN Ko Motoki Graduate School of Environmental, Life and Natural Science and Technology, Okayama University Saki Kobayashi Graduate School of Environmental, Life and Natural Science and Technology, Okayama University Kazusa Nishimura Graduate School of Environmental, Life and Natural Science and Technology, Okayama University Yu Kinoshita Graduate School of Agriculture, Kyoto University Makoto Kashima Faculty of Science, Department of Biomolecular Science, Toho University Koichiro Ushijima Graduate School of Environmental, Life and Natural Science and Technology, Okayama University Tanjuro Goto Graduate School of Environmental, Life and Natural Science and Technology, Okayama University Ken-ichiro Yasuba Graduate School of Environmental, Life and Natural Science and Technology, Okayama University Munetaka Hosokawa Faculty of Agriculture, Kindai University Graft-mediated floral induction is a classical yet promising breeding technique that accelerates seed production and shortens generation time in crops. However, its application remains limited to a few species because floral induction is often unstable. Even among florally induced rootstocks, grafted scions can differ in their flowering response depending on rootstock genotype, but the genetic basis of this variation remains unclear. Here, using a Brassicaceae grafting model, we investigated two early-bolting radish (Raphanus sativus) accessions differing in their ability to induce flowering. We focused on a significant difference in FLOWERING LOCUS T (FT) expression between these accessions and identified two quantitative trait loci (QTLs) associated with FT levels. Transcriptomic and genomic analyses revealed that both QTLs harbored previously unreported disrupted alleles of FLOWERING LOCUS C (FLC) homologs, key floral repressors involved in vernalization, which showed reduced expression and produced defective transcripts. Grafting experiments demonstrated that these disrupted FLC alleles enhanced floral induction, with RsFLC1 having a major effect. Our results indicate that the FT expression threshold required for graft-mediated floral induction is higher than that for rootstock flowering itself and that this threshold is reached when FLC-mediated repression is substantially reduced. These alleles were inferred to have originated from weedy radish (Raphanus raphanistrum), likely contributing to early flowering in disturbed environments. This study suggests that exploring genetic variations in FT expression is an effective strategy to develop highly florigenic rootstocks, thereby broadening the application of graft-mediated floral induction in crop breeding. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2751-1219 5 9 2026 Proton‐Radiation‐Tolerant Silicon Photonic Charge Sensor for Spacecraft Applications e70208 EN Wataru Takahama Department of Physics and Electronics, Osaka Metropolitan University Kosei Otsuka Department of Physics and Electronics, Osaka Metropolitan University Ayumi Ishihara Department of Physics and Electronics, Osaka Metropolitan University Rikuto Hojo Department of Space Systems Engineering, Kyushu Institute of Technology Tomofumi Mogami ElectrostaticEngineering DEPT, Kasuga Denki INC Kazuhiro Toyoda Department of Space Systems Engineering, Kyushu Institute of Technology Kohtaku Suzuki Research and Development, The Wakasa Wan Energy Research Center Yasushi Takahashi Faculty of Environmental, Life, Natural Science and Technology,Okayama University Silicon waveguides are promising platforms for spacecraft potential sensing owing to their compactness and immunity to electromagnetic interference. However, proton-induced optical absorption in operating silicon waveguides has not been quantitatively clarified, despite their direct exposure to the space radiation environment during spacecraft operation. Here, we present a systematic elucidation of proton-radiation effects on a photonic charge sensor based on silicon photonic crystal waveguides. During proton irradiation at 20 keV, we quantitatively evaluate the increase in optical absorption under device operation and find that a fluence of 1.0 ×1014 cm− 2 induces an additional absorption coefficient of approximately 0.41 cm− 1 . We further demonstrate that the sensor retains its ability to measure spacecraft potential even after exposure to a high proton fluence of 1.0 ×1015 cm− 2 , confirming its intrinsic radiation tolerance. These results establish the radiation robustness of silicon-waveguide- based sensing mechanisms and provide the first quantitative basis for implementing photonic charge sensors in radiation-rich spacecraft environments. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1349-0079 68 6 2026 Synaptic transmission in Type III taste cells 100819 EN Hinata Tatsukawa Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kengo Horie Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryusuke Yoshida Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Type III taste cells are the primary taste receptor cells that form conventional chemical synapses with gustatory nerve fibers. Since the first ultrastructural identification of synaptic vesicles in Type III cells, numerous studies have demonstrated that these cells have synapse-associated proteins and vesicular release machinery that is similar to that in the central nervous system.<br> Highlight: This review summarizes historical and ultrastructural studies describing synaptic vesicles in taste bud cells across a range of animal species. The classical mechanisms of chemical synaptic transmission in the central nervous system are then outlined, followed by review studies demonstrating the expression of synapse-associated proteins in taste bud cells, with particular emphasis on the putative mechanisms of synaptic transmission in Type III taste cells. Finally, the current evidence for candidate neurotransmitters, including 5-hydroxytryptamine, gamma-aminobutyric acid, noradrenaline, acetylcholine, and ATP, is discussed.<br> Conclusion: Although several proteins related to conventional chemical synapses in the central nervous system and some candidate neurotransmitters have been identified in Type III cells, their contributions to sour taste transmission have not been fully elucidated. Further molecular and physiological studies are required to establish their roles in the synaptic transmission of sour taste signals from Type III cells. No potential conflict of interest relevant to this article was reported.

American Physical Society (APS) Acta Medica Okayama 0031-9007 137 9 2026 Strain-Tuned Nodal Superconductivity in the Charge-Ordered Kagome Metal CsV3⁢Sb5 096003 EN Yusuke Takeuchi Department of Physics, Okayama University Akito Kobayashi Department of Physics, Okayama University Saki Uchida Department of Physics, Okayama University Takumi Nagao Department of Physics, Okayama University Seigo Ogawa Department of Physics, Okayama University Rui Zhou Institute of Physics, Chinese Academy of Sciences, and Beijing National Laboratory for Condensed Matter Physics Shinji Kawasaki Department of Physics, Okayama University Fei Song Fujian Provincial Collaborative Innovation Center for Advanced High-Field Superconducting Materials and Engineering, College of Physics and Energy, Fujian Normal University Hao Ni Fujian Provincial Collaborative Innovation Center for Advanced High-Field Superconducting Materials and Engineering, College of Physics and Energy, Fujian Normal University Yong Zhao Fujian Provincial Collaborative Innovation Center for Advanced High-Field Superconducting Materials and Engineering, College of Physics and Energy, Fujian Normal University Guo-qing Zheng Department of Physics, Okayama University The nature of the superconducting pairing symmetry in the kagome metal CsV3⁢Sb5 and its relationship with the charge density wave (CDW) order are central unresolved issues. Here, we investigate the evolution of superconductivity in CsV3⁢Sb5 under in situ uniaxial pressure using 121Sb nuclear quadrupole resonance (NQR). We find that tensile strain significantly enhances the superconducting transition temperature, 𝑇c, while the CDW remains unchanged, demonstrating that superconductivity can be tuned independently of the bulk charge order. At a tensile strain of 𝜖 =+0.90%, the nuclear spin-lattice relaxation rate reveals a remarkable double transition: an upper transition at 𝑇c⁢1=3.6  K to a nodal gap state, and a lower one at 𝑇c⁢2=3.0  K characterized by a nodeless gap. These results evidence degenerate superconducting states with different gap symmetry in the kagome metal at ambient pressure which split under strain. Our Letter demonstrates a high tunability of superconductivity by uniaxial pressure. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2198-3844 2026 SPRED2 Negatively Regulates CD8+ T Cell-Mediated Antitumor Immunity in Breast Cancer e77909 EN Miao Tian 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 Kun Zhao Department of Oral Rehabilitation and Regenerative 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 Tong Gao Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ziyi Wang Department of Advanced International and Information Dentistry, Faculty 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 Activation of the RAS/RAF/ERK pathway is crucial for adaptive immunity. Here, we provide evidence that Sprouty-related EVH1 domain containing 2 (SPRED2), an endogenous inhibitor of this pathway, negatively regulates CD8+ T cell-mediated antitumor immunity in breast cancer. In EO771 and 4T1 mouse models, Spred2−/− mice exhibit reduced tumor growth, with lower endpoint lung metastatic burden in the 4T1 model, accompanied by increased T-cell infiltration and activation. Spred2−/− T cells show enhanced cytokine expression, proliferation,survival, in vitro cytotoxicity, and memory-like phenotypes, particularly among CD8+ T cells. Adoptive transfer of Spred2−/− CD8+ T cells into tumor-bearing wild-type hosts similarly reduces endpoint lung metastatic burden. MEK inhibition with U0126 attenuates increased interferon-gamma and granzyme B expression in Spred2−/− CD8+ T cells. Transcriptomic analyses reveal an inverse correlation between SPRED2 expression and antitumor CD8+ T cell states in both humans and mice. In tumor-infiltrating T cells from patients with breast cancer, SPRED2low T cells show enriched effector and cytotoxicity programs and are associated with “immune-hot” tumors, whereas survival associations vary with CD8+ T cell context. Collectively, these findings suggest that SPRED2 functions as a cell-intrinsic negative regulator of CD8+ T-cell activation and highlight its potential as a therapeutic target to enhance T cell–based cancer immunotherapy. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0361-8609 100 4 2025 Exploring the Clinical Diversity of Castleman Disease and TAFRO Syndrome: A Japanese Multicenter Study on Lymph Node Distribution Patterns 592 605 EN Mizuna Otsuka Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Tomohiro Koga Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Remi Sumiyoshi Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Shoichi Fukui Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Yuko Kaneko Division of Rheumatology, Department of Internal Medicine Keio University School of Medicine Tokyo Japan Takayuki Shimizu Division of Hematology, Department of Medicine, Keio University School of Medicine Atsushi Katsube Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine Shingo Yano Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine Yasufumi Masaki Department of Hematology and Immunology, Kanazawa Medical University Makoto Ide Department of Hematology, Takamatsu Red Cross Hospital Hajime Yoshifuji DDepartment of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University Masayasu Kitano Department of Collagen Disease and Rheumatology, Sumitomo Hospital Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Naoki Sawa Nephrology Center and Department of Rheumatology, Toranomon Hospital Kajigaya Hiroaki Niiro Department of Clinical Immunology and Rheumatology/Infectious Disease, Kyushu University Hospital Naoya Nakamura Department of Pathology, Tokai University School of Medicine David C. Fajgenbaum Center for Cytokine Storm Treatment & Laboratory, University of Pennsylvania Frits van Rhee Myeloma Center, University of Arkansas for Medical Sciences Atsushi Kawakami Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Individuals diagnosed with Castleman disease (CD) and TAFRO syndrome (characterized by thrombocytopenia, anasarca, fever, bone marrow fibrosis, and organomegaly) displays a wide range of clinical symptoms, including varying patterns of lymph node enlargement, systemic inflammation, and impaired organ function. Some patients may present with both CD and TAFRO syndrome concurrently. A retrospective study conducted across multiple centers in Japan examined 321 cases to determine if the quantity and position of swollen lymph nodes could forecast the clinical progression and intensity of these conditions. Interestingly, the study revealed that patients with TAFRO syndrome exhibited lymphadenopathy across all ranges of lymph node region counts. Moreover, no specific clinical patterns were associated with the number of affected lymph node regions in CD patients, regardless of whether they also had TAFRO syndrome. These results enhance our understanding of the clinical variability in CD and TAFRO syndrome, suggesting that a comprehensive clinical evaluation, rather than relying solely on lymph node count, is crucial for effectively managing these conditions. Additional studies are required to establish reliable diagnostic markers and to predict disease severity at the time of diagnosis, ultimately improving patient outcomes. No potential conflict of interest relevant to this article was reported.

Japan Medical Association Acta Medica Okayama 2433-3298 8 2 2025 Unraveling Causality: Innovations in Epidemiologic Methods 323 337 EN Etsuji Suzuki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University For several decades, the counterfactual model and the sufficient cause model have shaped our understanding of causation in biomedical science and, more recently, the link between these two models has enabled us to obtain a deeper understanding of causality. In this article, I provide a brief overview of these fundamental causal models using a simple example. The counterfactual model focuses on one particular cause or intervention and gives an account of the various effects of that cause. By contrast, the sufficient cause model considers sets of actions, events, or states of nature which together inevitably bring about the outcome under consideration. In other words, the counterfactual framework addresses the question “what if?” while the sufficient cause framework addresses the question “why does it happen?” Although these two models are distinct and address different causal questions, they are closely related and used to elucidate the same cause-effect relationships. Importantly, the sufficient cause model makes clear that causation is a multifactorial phenomenon, and it is a “finer” model than the counterfactual model; an individual is of one and only one response type in the counterfactual framework, whereas an individual may be at risk of none, one, or several sufficient causes. Understanding the link between the two causal models can provide greater insight into causality and can facilitate the use of each model in appropriate contexts, highlighting their respective strengths. I will briefly present three topics of interest from our research: the relationship between the concepts of confounding and of covariate balance; distinctions between attributable fractions and etiologic fractions; and the identification of operating mediation and mechanism. It is important to scrutinize observed associations in a complementary manner, using both the counterfactual model and the sufficient cause model, employing both inductive and deductive reasoning. This holistic approach will better help us to unravel causality. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2073-4395 16 16 2026 Genetic Dissection and Fine-Mapping of QTL for Salinity Tolerance at the Reproductive Stage on Chromosome 2 of Rice Variety Nona Bokra 1518 EN Farjana Rauf Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tran Thi Thu Hien Graduate School of Environmental and Life Science, Okayama University Nguyen Thi Thu Thuy Graduate School of Environmental and Life Science, Okayama University Asami Tomita Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshihiko Hirai Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Soil salinity is a major constraint limiting rice productivity, particularly at the reproductive stage. To elucidate the genetic basis of reproductive stage salinity tolerance, this study validated and fine-mapped quantitative trait loci (QTL) for yield-related traits using a salinity-tolerant line SL506, identified through screening of Nona Bokra–CSSLs in a Koshihikari background. In 2016, the F2 population derived from SL506/Koshihikari was evaluated under long-term salt stress; three QTLs associated with plant dry weight, panicle number, and grain weight were detected on chromosome 2. In 2023, validation analysis using F3 individuals confirmed the presence of these QTLs. Subsequent fine-mapping using F4 near-isogenic lines (NILs) delimited the QTL to a 1.7 Mb interval and high-resolution mapping using an F5 recombinant population progressively refined it to a 473 kb genomic region containing 69 annotated genes. Variant Effect Predictor analysis identified 15 deleterious nonsynonymous variants (SIFT < 0.05) in six candidate genes. Based on annotated gene functions, predicted variant effects, and their membership in stress-related gene families, OsPP2C24, OsFbox102, and OsWAK14 were suggested as the most promising candidate genes underlying qPDW2. These findings provide insights into the genetic basis of reproductive-stage salinity tolerance from valuable resources for the future improvement of salt tolerance and yield stability in rice. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2673-7655 6 2 2026 Effects of Different Heading Dates on Agronomic and Yield-Related Traits Under Salt Stress in Rice 28 EN Sadia Afrin Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sayuri Ito School of Agriculture, Okayama University M M Emam Ahmed Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Shuto Ogino School of Agriculture, Okayama University Asami Tomita Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshihiko Hirai Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Salinity is a major abiotic stress limiting rice production worldwide. This study aims to elucidate the effects of heading date on salt tolerance in rice. Five near-isogenic lines (NILs) developed from the SL2038/Koshihikari backcross population were grown with or without salt stress. SL2038 is a salt-tolerant line with delayed heading (~18 days) compared to the salt-sensitive background Koshihikari. The results showed that late-heading NILs produced significantly higher plant dry weight, panicle weight, percentage of filled grains, and grain weight (p < 0.05) under long-term salt stress. In Koshihikari, which exhibited delayed heading due to long-day treatment, the percentage of white heads was low, and panicle and grain weights were significantly higher under salt stress. Experiments with different sowing times indicated that late heading, such as sowing in June, resulted in higher grain weights. This is the first report to assess the impact of heading date on agronomic and yield-related traits under salt stress. In conclusion, even with a prolonged salt treatment period, heading during periods of low temperature and solar radiation results in higher grain weight under salt stress. This is proposed as one of the strategies for salt escape. These findings can be used to improve rice yield and implement crop management in salt-affected regions. No potential conflict of interest relevant to this article was reported.

Walter de Gruyter GmbH Acta Medica Okayama 2294-1932 2026 Direct evidence for water-filled yet hydraulically isolated xylem vessels in two temperate tree species 1 14 EN Mayumi Y. Ogasa Kansai Research Center, Forestry and Forest Products Research Institute Yasuhiro Utsumi Ashoro Research Forest, Kyushu University Kenichi Yazaki Hokkaido Research Center, Forestry and Forest Products Research Institute Naoko H. Miki Faculty of Environmental, Life, Natural Science and Technology Kenji Fukuda Graduate School of Agricultural and Life Sciences, The University of Tokyo Xylem vessels in sapwood are typically interpreted as either conductive or non-functional following embolism or occlusion, implicitly assuming that the presence of water within the lumen reflects participation in the transpiration stream. However, the relationship between lumen water content and hydraulic connectivity has rarely been examined directly at the cellular level. In this study, we combined cryo-scanning electron microscopy and fluorescence microscopy to compare lumen water status with hydraulic connectivity on the same xylem surface in current-year xylem of Carpinus tschonoskii and Aria alnifolia, using tension-driven dye uptake to identify conductive vessels. Most vessels were stained and water-filled, consistent with functional conduits, whereas unstained gas-filled vessels corresponded to embolized conduits. Notably, certain vessels retained water despite lacking dye signals, indicating hydraulic isolation from the conductive xylem network. Although these vessels represented a minor fraction of the conduit population, their occurrence suggests that the traditionally binary classification should be expanded to incorporate an additional conduit function. These vessels were observed in both species, suggesting that hydraulically disconnected vessels represent a common phenomenon across species. These findings reveal previously underrecognized heterogeneity in xylem hydraulic organisation and demonstrate that conduit status cannot always be inferred from the presence of water alone. Recognising this intermediate condition refines current interpretations of xylem function and highlights the value of integrating high-resolution imaging with hydraulic measurements. No potential conflict of interest relevant to this article was reported.

John Benjamins Publishing Company Acta Medica Okayama 0019-0829 2026 Making alliterative collocations memorable: Does vocalisation help? EN Satoshi Yamagata Okayama University Mariko Abe Okayama University Anna Siyanova-Chanturia Victoria University of Wellington Collocations are a key component of second language (L2) mastery. Yet, their acquisition poses major challenges to L2 learners. One potential solution to this difficulty is employing the mnemonic effect of alliteration (e.g., professional practice). In the present study, 230 Japanese EFL university students learnt alliterative and non-alliterative collocations (e.g., primary purpose vs. primary care) under vocalised and non-vocalised conditions in a within-subject design. Vocalisation frequencies were operationalised (none, once, three, and five times) over four weeks to examine potential differences across repetition frequencies. Immediate and delayed productive recall post-test assessed collocational uptake. Results showed that alliterative collocations yielded greater gains than non-alliterative ones when vocalisation was involved, suggesting a conditional benefit of vocalisation in combination with phonological salience. A modest advantage was observed in the three-times vocalisation condition in the immediate post-test; however, it was not reliably maintained at the delayed post-test. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1058-8388 2026 MIT/TFE family transcription factors, Mitf and Tfec, redundantly promote pigment cell differentiation and retinal epithelium pigmentation in teleosts 1 15 EN James Lister Department of Human and Molecular Genetics and Massey Cancer Center, Virginia Commonwealth University School of Medicine Keisuke Sugiwaka Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University Tetsuaki Kimura Department of Basic Biology, School of Life Science, Graduate University of Advanced Studies (SOKENDAI) & Laboratory of Bioresources, National Institute for Basic Biology Rieko Tanaka World Medaka Aquarium, Nagoya Higashiyama Zoo and Botanical Gardens Makoto Goda Institute of Photonics Medicine, Hamamatsu University School of Medicine Hikaru Kobayashi Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University Chikako Inoue R&D Fish Breeding Group, Regional Fish Institute, Ltd. Kawilarang W. A. Masengi Faculty of Fisheries and Marine Science, Sam Ratulangi University Kazunori Yamahira Tropical Biosphere Research Center, University of the Ryukyus Kiyoshi Naruse Department of Basic Biology, School of Life Science, Graduate University of Advanced Studies (SOKENDAI) & Laboratory of Bioresources, National Institute for Basic Biology Satoshi Ansai Ushimado Marine Institute, Graduate School of Natural Science and Technology, Okayama University Robert N. Kelsh Department of Life Sciences, University of Bath Masahiko Hibi Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University Hisashi Hashimoto Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University Background: Transcription factors of the MIT/TFE family―mitfa, mitfb, and tfec―play essential roles in specifying pigment cells derived from neural crest cells in vertebrates. In teleosts, which possess multiple pigment cell types, these factors exhibit partially redundant but largely distinct functions across different pigment lineages. We previously reported that the combined loss of mitfa and mitfb leads to a complete absence of melanophores, xanthophores, and leucophores in medaka.<br> Results: Here, we describe newly generated hypomorphic alleles of mitfa and mitfb, which result in delayed melanophore development. Using these hypomorphic mutants in combination with a newly generated null allele of tfec, we show that Tfec can partially compensate for the loss of Mitfa and Mitfb in melanophore, xanthophore, and leucophore differentiation. Consistent with previous findings in zebrafish, loss of tfec alone results in the complete absence of iridophores. Importantly, simultaneous null mutations in all three genes cause a complete loss of all four chromatophore types and lead to defective pigmentation of the retinal pigmented epithelium (RPE), which is not derived from the neural crest in both Oryzias species and in zebrafish. Using an RPE-specific marker, we further show that the RPE is specified and structurally intact but fails to melanize.<br> Conclusions: These findings indicate that the redundant functions of Mitfa, Mitfb, and Tfec are not only essential for the specification of diverse pigment cell types but also critical for RPE pigmentation. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0022-3751 604 18 2026 Integrative simulation analysis of myocardial ischaemia–reperfusion injury 7640 7662 EN Takao Shimayoshi Center for Artificial Intelligence and Mathematical Data Science, Okayama University Ayako Takeuchi Department of Physiology and Biophysics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Matsuoka Department of Integrative and Systems Physiology, Faculty of Medical Sciences, University of Fukui Cardiac ischaemia, reduced coronary blood flow, causes significant damages to the heart, and paradoxically reperfusion, restored flow after ischaemia, often results in more severe injury. Although the mechanisms underlying cardiac ischaemia–reperfusion injury have been intensively investigated, effective therapeutic strategies applicable during reperfusion to mitigate this damage have not been established yet. To obtain more insights into the mechanisms underlying ischaemia–reperfusion injury, and to explore effective methods to relieve reperfusion injury, we developed a comprehensive mathematical model of ventricular myocyte, implementing excitation–contraction (E–C) coupling, cytosolic and mitochondrial pH regulation, pH dependence of major components of E–C coupling and cellular energy metabolism, including mitochondrial oxidative phosphorylation. The mathematical model successfully reproduced experimentally observed findings on cardiac ischaemia–reperfusion injury, such as intracellular and extracellular acidosis, cytosolic Na+ overload, cytosolic Ca2+ overload, mitochondrial dysfunction, action potential shortening and contraction failure. It was found that the reperfusion-induced exacerbation of Na+i, Ca2+i overloads was mainly caused by insufficient production of NADH, which is used in mitochondrial oxidative phosphorylation to synthesize ATP for Na+/K+ pump and sarcoplasmic/endoplasmic reticulum Ca2+ pump (SERCA) to expel accumulated cytosolic Na+ and Ca2+, respectively. It was suggested that the preservation of mitochondrial NADH production, attenuation of ATP consumption via SERCA or contraction for a short period or activation of the Na+/K+ pump during reperfusion mitigates reperfusion injury. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2044-6055 16 8 2026 Study protocol for a phase II clinical trial evaluating the safety and efficacy of favipiravir injection combined with oseltamivir in influenza treatment e106715 EN Sayaka Hikida Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Hidetoshi Nomoto Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Yukari Uemura Laboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health Security Tadaki Suzuki Department of Infectious Disease Pathology, National Institute of Infectious Diseases, Japan Institute for Health Security Koichi Izumikawa Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences Hiroki Ohge Project Research Center for Nosocomial Infectious Diseases, Hiroshima University Masaya Yamato Infectious Diseases Center, Rinku General Medical Center Yasuyuki Kato Department of Infectious Diseases, International University of Health and Welfare Narita Hospital Ryota Hase Department of Infectious Diseases, Japanese Red Cross Narita Hospital Tetsuji Aoyagi Department of Clinical Microbiology and Infection, Tohoku University Graduate School of Medicine Hideharu Hagiya Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoko Nukui Department of Infection Control & Laboratory Medicine, Kyoto Prefectural University of Medicine Kazuko Yamamoto First Department of Internal Medicine, Division of Infectious, Respiratory, and Digestive Medicine, University of the Ryukyus Graduate School of Medicine Yoshio Takesue Chita Peninsula General Medical Organization, Rinku Hospital Kota Sawada Laboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health Security Yosuke Shimizu Laboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health Security Sho Miyamoto Department of Infectious Disease Pathology, National Institute of Infectious Diseases, Japan Institute for Health Security Namiko Tamura Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Kozue Takahashi Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Sho Saito Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Kazuki Miyazaki Center for Clinical Sciences, Japan Institute for Health Security Eriko Morino Center for Clinical Sciences, Japan Institute for Health Security Daisuke Tokita Center for Clinical Sciences, Japan Institute for Health Security Norio Ohmagari Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Introduction Older adults are at an increased risk of influenza-related hospitalisation and mortality due to a combination of risk factors. Severe influenza and excess mortality in this population remain major public health concerns, underscoring the need for novel treatment strategies.<br> Methods and analysis This multicentre, investigator-initiated, randomised, double-blind clinical trial evaluated the efficacy and safety of the investigational drug favipiravir injection (T-705IV) in combination with oseltamivir phosphate, compared with oseltamivir monotherapy in hospitalised patients with influenza aged ≥65 years. Both T-705IV and oseltamivir phosphate will be administered for 5 days. The primary endpoint is time from randomisation to recovery within 15 days. Recovery is defined as either actual hospital discharge or sustained clinical status permitting discharge for 3 consecutive days. Clinical status will be assessed using a 7-point ordinal scale based on hospitalisation status and oxygen requirement. The primary analysis employs a Bayesian Cox proportional hazards model with a non-informative prior to estimate the posterior probability that the HR exceeds 1.0. The secondary endpoints include the distribution of 7-point scale scores over a 29-day period; rates of clinical worsening at days 15 and 29; duration of fever; all-cause mortality; intensive care unit admission within 29 days; pneumonia complication rate at 15 days; and changes in viral titre and viral RNA load on days 1, 2, 3 and 7. Safety will be assessed through the collection of adverse events (AEs) up to day 29. Pharmacokinetic evaluation will include measurement of plasma favipiravir concentrations on day 3. The planned sample size is 80 patients (40 per group).<br> Ethics and dissemination Written informed consent will be obtained from all participants. This study was approved by the Center Hospital of the National Center for Global Health and Medicine Institutional Review Board (approval number: NCGM-I-022-24a) and registered in the Japan Registry of Clinical Trials. Study findings will be disseminated through peer-reviewed publications and/or presentations at academic conferences.<br> Trial registration number jRCT2031240586, No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 2576-098X 2026 Complete genome sequence of Helicobacter pylori strain NY43 harboring bacteriophage KHP30 e00747-26 EN Michiko Takahashi Department of Surgery, Kochi Medical School, Kochi University Hiromichi Maeda Department of Surgery, Kochi Medical School, Kochi University Satoru Seo Department of Surgery, Kochi Medical School, Kochi University Hiroaki Takeuchi Department of Medical Laboratory Sciences, Health and Science, International University of Health and Welfare Graduate School Jumpei Uchiyama Department of Infectious Diseases, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University Shigenobu Matsuzaki Department of Surgery, Kochi Medical School, Kochi University The Helicobacter pylori NY43 strain spontaneously releases the bacteriophage (phage) KHP30. Here, we report the complete genome sequence of H. pylori NY43. In addition to the chromosome of H. pylori NY43, we successfully obtained the complete sequence of the episomal prophage KHP30. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2041-1723 17 1 2026 RNase-mediated defence and its association with SCCmec in Staphylococcus aureus 9986 EN Kohei Kondo Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Aa Haeruman Azam Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Junzo Hisatsune Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Shinjiro Ojima Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Kotaro Chihara Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Tomohiro Nakamura Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Azumi Tamura Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Wakana Yamashita Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Satoshi Nakano Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Shoko Kutsuno Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Yo Sugawara Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Masayuki Amagai Department of Dermatology, Keio University School of Medicine Tetsuo Yamaguchi Department of Microbiology and Infectious Diseases, Toho University School of Medicine Yoshikazu Ishii Department of Microbiology and Infectious Diseases, Toho University School of Medicine Koichi Watashi Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Yoshimasa Takahashi Research Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health Security Kotaro Kiga Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Motoyuki Sugai Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security The rise of antibiotic resistance in Staphylococcus aureus is a major threat to global health. Resistance often emerges when bacteria acquire foreign DNA elements, such as the SCCmec cassette that makes strains resistant to nearly all β-lactam antibiotics. Yet, not all S. aureus lineages take up these elements equally, raising the question of what prevents some strains from becoming drug-resistant. Here we identify a previously unknown defence factor that explains this mystery in a common skin lineage (ST188), frequently isolated from patients with atopic dermatitis. Such defence factor is encoded by a gene, which we name sadR, that is present in methicillin-susceptible ST188 strains but absent from resistant counterparts. SadR exhibits RNase activity that provides anti-bacteriophage and anti-plasmid defence, thus acting as a barrier to the uptake of mobile genetic elements. Gene sadR is found in methicillin-susceptible strains in S. aureus lineages other than ST188, and is consistently located adjacent to rlmH, the canonical SCCmec integration site. Moreover, SadR homologues are widespread across staphylococci and other bacteria suggesting a previously unrecognised family of RNase-based defence systems. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 8756-758X 2026 Fatigue Life Evaluation Using the Damage‐Equivalent Strain for 7075‐T6 Aluminum Alloy Under Bending and Torsion Bending Vibrations EN Junji Sakamoto Faculty of Environmental, Life, Natural Science and Technology, Okayama University Naoya Tada Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takeshi Uemori Faculty of Environmental, Life, Natural Science and Technology, Okayama University The vibrations caused by external factors (such as fluids) or internal factors often pose strength-related problems in mechanical and structural components. Although several studies have investigated the material fatigue characteristics during vibration, reports on complex vibration modes such as torsion bending are limited. In this study, we addressed this gap by conducting experiments and finite element analyses on I- and L-shaped aluminum alloy specimens under bending and torsion bending vibrations, respectively. We established a reliable method to estimate the strain at the notch by utilizing the strain measured at a position outside the notch and a ratio derived from finite element analysis. This method allows for accurate assessment of the critical strain history without interfering with crack observation. Using the strain range at the crack initiation site effectively unified the fatigue life evaluation for both specimens. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0031-3998 2026 Long-term association between the COVID-19 pandemic and language development at 3 years of age EN Rumi Matsuo Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazue Nakamura Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Few studies have examined the long-term association between the COVID-19 pandemic and language development in preschoolers or its effect modifiers. We therefore examined this association during health checkups of 3-year-olds in Japan.<br> Methods: This repeated cross-sectional study included 40,898 3-year-olds who underwent checkups in Okayama City, Japan. We compared children examined before (2017–2019) and during the pandemic (2020–2023). The primary outcome was physician-determined risk of language difficulties. The secondary outcome was children’s infrequent questions using words such as “what,” “who,” and “where.” Modified Poisson regression estimated RRs adjusted for confounders. Subgroup analyses examined effect modification by sex, childcare setting, and family size.<br> Results: The COVID-19 pandemic was associated with increased risk of language difficulties (RR 1.52, 95% CI 1.35–1.72). The association peaked in fiscal year 2021 and remained elevated throughout the pandemic. Secondary outcome showed elevated risk (RR 1.16, 95% CI 1.05–1.29). Girls and home-care children showed higher RRs than boys and preschool attendees.<br> Conclusions: The COVID-19 pandemic was associated with risk of language difficulties among 3-year-old children, with associations varying by sex and childcare setting. These findings suggest the importance of maintaining social interaction opportunities for young children during public health crises. No potential conflict of interest relevant to this article was reported.

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 49 8 2026 Impact of Adjusted Creatinine Clearance on Carboplatin Dosing in Endometrial Cancer: A Retrospective Study 1285 1290 EN Kentaro Katayama Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Makio Imamura Department of Clinical Support, Kurashiki Medical Center Takashi Uehara Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Carboplatin (CBDCA) dosing is commonly determined using the Calvert formula, with creatinine clearance (Ccr) estimated by the Cockcroft–Gault formula. In Japan, where serum creatinine (sCr) is usually measured enzymatically, unadjusted Ccr may overestimate glomerular filtration rate and lead to CBDCA overdosing. We retrospectively compared treatment exposure, hematologic toxicity, and exploratory oncologic outcomes in patients with endometrial cancer who received postoperative paclitaxel plus CBDCA therapy. Patients were grouped according to whether CBDCA dosing was based on the conventional Cockcroft–Gault formula (CG group) or on adjusted Ccr calculated by adding 0.2 mg/dL to sCr (adjusted group). The incidence of Grade ≥3 neutropenia was significantly lower in the adjusted group than in the CG group. The 5-year progression-free survival (PFS) rate was numerically lower in the adjusted group than in the CG group, although no statistically significant difference was observed between the groups. Because the number of PFS events was limited, the effect of adjusted Ccr-based dosing on oncologic outcomes remains uncertain. These findings suggest that adjusted Ccr-based dosing may reduce hematologic toxicity in routine clinical practice. However, given the limited number of PFS events and the wide uncertainty in survival estimates, further studies are needed to clarify its impact on oncologic outcomes. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0969-806X 251 2027 A rule-based calculation approach to derive bone-suppressed chest X-ray images using photon-counting techniques 114493 EN Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Mana Mitani Division of Radiology, Medical Support Department, Okayama University Hospital Daiki Kobayashi Graduate School of Medical Sciences, Kanazawa University Noriaki Akagi Division of Radiology, Medical Support Department, Okayama University Hospital 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 Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University Improving the visibility of lung nodules, which are often hidden by bone shadows and difficult to identify, remains a challenge in chest radiography. This study aims to develop an algorithm for generating novel bone-suppressed images using photon-counting techniques. The core idea of our algorithm is to fit photon interaction cross-sections to X-ray attenuation data measured with photon-counting detectors. Based on further calculations using the derived fitting coefficients, both density (ρ) and amount-of-substance concentration (mol) were determined. The product of these values produced a ρ×mol image exhibiting a clear bone-suppression effect. We conducted a virtual chest imaging simulation using 10 patient datasets acquired via clinical photon-counting computed tomography (PC-CT). The CT images were converted into ρ×mol images following the proposed processing procedure, and two-dimensional chest images were generated through projection. Quantitative evaluations confirmed that the proposed images achieved sufficient bone suppression. Furthermore, commercial software provided by a vendor was used to generate bone-suppressed images from conventional images projected from CT data. A comparable bone-suppression effect on the ribs was observed between the vendor-generated images and our proposed images, while lesion visibility (e.g., lung nodules) was preserved. Additionally, bone-suppression effects in our images were observed in the vertebrae and clavicles located outside the lung fields. Our research demonstrates the value of constructing general X-ray imaging systems using photon-counting detectors. No potential conflict of interest relevant to this article was reported.

AIP Publishing Acta Medica Okayama 0021-9606 165 10 2026 Scaled-charge ion force field optimized for individual ion partial molar volumes in water 104508 EN Aoi Taira Department of Chemistry, Faculty of Science, Okayama University Hiroyuki Katsuto Department of Chemistry, Faculty of Science, Okayama University Kanon Nakao Department of Chemistry, Faculty of Science, Okayama University Tomonari Sumi Graduate School of Engineering, Muroran Institute of Technology Kenichiro Koga Department of Chemistry, Faculty of Science, Okayama University We present an ion partial molar volume force field for common monovalent and divalent ionic species, including Li+, Na+, K+, Cs+, Mg2+, Ca2+, F−, Cl−, Br−, I−, OH−, and H3O+. When combined with the TIP4P/2005 water model, the force field enables quantitative investigations of ion-specific effects in both bulk and interfacial properties. The iPMV force field is developed based on a single guiding principle: the ion–water interaction parameters are optimized such that the experimental partial molar volume of each individual ion at infinite dilution―determined via the ultrasonic vibrational potential method―is reproduced by construction. An exception is made for the hydronium ion, for which we also provide an alternative interface-optimized model. The force field employs a charge scaling factor of 0.75 and adopts the Lorentz–Berthelot combining rules for cross-Lennard-Jones interactions, with specific modifications for divalent cations. A distinctive feature of the iPMV force field is that, despite its straightforward design, a single set of ion parameters consistently reproduces a wide range of experimental properties―from volumetric and interfacial properties to salting-out/in effects and transport coefficients. This robust performance suggests a fundamental correlation between the partial molar volumes of individual ions and the broader physical properties of aqueous electrolyte solutions. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2197-4284 13 1 2026 Carbon solubility and liquid–liquid immiscibility in Fe–C–S ternary system up to 6 GPa: implications for the core of small planetary bodies 60 EN Bin Zhao Institute for Planetary Materials, Okayama University Guillaume Morard UMR CNRS 7590, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne Université Geeth Manthilake Laboratoire Magmas et Volcans, Université Clermont-Auvergne Paraskevas Parisiades UMR CNRS 7590, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne Université Jing Yang Earth and Planets Laboratory, Carnegie Institution for Science Yingwei Fei Earth and Planets Laboratory, Carnegie Institution for Science Yann Le Godec UMR CNRS 7590, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne Université Nozomi Kondo Institute for Planetary Materials, Okayama University Takashi Yoshino Institute for Planetary Materials, Okayama University Daniele Antonangeli UMR CNRS 7590, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Muséum National d’Histoire Naturelle, Sorbonne Université High-pressure, high-temperature experiments were conducted in a multi-anvil press using seven different starting compositions to investigate the phase relations of Fe–C–S liquids at pressures up to 6 GPa and temperatures up to 2000 K. Quenched samples revealed immiscible C-rich and S-rich metallic liquids at 2 and 4 GPa, manifesting as either large immiscible zones or emulsified smaller droplets. On the contrary, no immiscibility was observed at 5 or 6 GPa. At these higher pressures, the carbon solubility limit, significantly reduced by increasing sulfur content in the ternary liquid, prevents the formation of a liquid phase rich in both C and S. Our findings thus indicate that super-liquidus immiscibility in Fe-rich compositions does not occur at pressures above 5 GPa, due to the differential pressure dependence of C solubility and miscibility. The limited C solubility in S-rich liquids at higher pressures effectively suppresses immiscibility. Based on these results, terrestrial planetary bodies with fluid cores at pressures exceeding 5 GPa are unlikely to experience liquid–liquid immiscibility, even when both carbon and sulfur are abundant, as sulfur limits carbon solubility and promotes its exsolution. For the Moon, immiscibility-induced core stratification is not expected, though local emulsification could occur near the core–mantle boundary (CMB). In smaller bodies, a two-liquid Fe–C–S core may form at high temperatures, but progressive cooling may lead to graphite crystallization and the potential development of a graphitic crust. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0739-7240 98 2027 Transcriptional remodeling of local thyroid hormone metabolism is associated with feather growth termination in chicken wing feathers 107057 EN Masamichi Shinohara Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuri Nozawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hibiki Fukuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yu Takeuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sayaka Aizawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sakae Takeuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Feather elongation is sustained by continuous cell proliferation within the feather follicle; however, the molecular mechanisms responsible for feather growth termination remain poorly understood. In this study, we investigated molecular changes associated with feather growth termination by comparing two chicken wing feather types with contrasting growth characteristics: primary wing feathers and primary coverts. Histological and bromodeoxyuridine incorporation analyses demonstrated that primary wing feathers remained in an active growth phase, whereas primary coverts exhibited pulp regression, reduced cell proliferation, and characteristics of growth termination. Gene expression analyses showed that primary coverts exhibited reduced expression of prolactin receptor (PRLR), type 2 iodothyronine deiodinase (DIO2), and insulin-like growth factor 2 (IGF2), together with marked induction of the thyroid hormone (TH)-inactivating enzyme type 3 iodothyronine deiodinase (DIO3). In contrast, primary wing feathers exhibited relatively higher expression of PRLR, DIO2, and IGF2 than primary coverts, while maintaining consistently low DIO3 expression. Reporter assays showed increased IGF2 promoter activity following triiodothyronine (T3) treatment in all three independent experiments, although the increase did not reach statistical significance. Thus, the reporter assay provides only tentative support for T3 responsiveness of the IGF2 promoter, consistent with our previous in vivo and primary-culture findings showing T3-dependent increases in IGF2 expression. These coordinated transcriptional changes are consistent with remodeling of local TH metabolism during the transition from active feather growth to growth termination. While local TH concentrations and direct deiodinase activities remain to be quantified, and the causal relationship between PRL/PRLR signaling and DIO3 induction remains unresolved, this study provides a molecular framework for understanding how local endocrine regulation translates systemic hormonal signals into feather type-specific growth responses during avian feather development. Graphical abstract No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 0099-2240 2026 Interaction with the N-acetylgalactosamine moiety facilitates pore formation by Cry4Aa toxin, thereby increasing its toxicity e00714-26 EN Mohammad Tofazzal Hossain Howlader Department of Entomology, Bangladesh Agricultural University Taiyo Tsutsui Applied Chemistry and Biotechnology Program, School of Engineering, Okayama University Kouichi Saito Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tohru Hayakawa Applied Chemistry and Biotechnology Program, School of Engineering, Okayama University Cry4Aa is a mosquito-larvicidal toxin produced by Bacillus thuringiensis serovar israelensis. Cry4Aa exhibits a characteristic architecture comprising three domains (I, II, and III) and functions as a pore-forming toxin, consistent with many previously reported insecticidal Cry toxins. However, the mechanism preceding pore formation by Cry4Aa, including receptor recognition, remains to be elucidated. The present study examined the potential involvement of sugar moieties in the Cry4Aa mode of action, with a particular focus on the process of pore formation. Cry4Aa and the sugar N-acetylgalactosamine exhibited considerably increased binding affinity. Furthermore, N-acetylgalactosamine treatment significantly enhanced the toxicity of Cry4Aa against Culex pipiens mosquito larvae. In the presence of N-acetylgalactosamine, the binding of Cry4Aa to phosphatidylcholine liposomes increased by 1.4-fold. The presence of this sugar did not affect the single-channel conductance of Cry4Aa pores formed in artificial lipid bilayers; however, it did appear to increase the number of Cry4Aa pores per designated area. In silico molecular docking analysis revealed promising binding sites within the cavity, surrounded by the Cry4Aa domains. These results suggest that the interaction of Cry4Aa with N-acetylgalactosamine moieties is a vital step in the process of pore formation. This interaction may induce a conformational change in the Cry4Aa molecule that facilitates its insertion into the target membrane. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1010-6030 478 2026 Deep-blue solid-state emission from Ternaphthalene: Photophysical tuning via multi-chromophore architectures 117156 EN Minoru Yamaji Division of Molecular Science, Graduate School of Science and Engineering, Gunma University Kengo Suzuki Hamamatsu Photonics K.K. Hideki Okamoto Department of Chemistry, Faculty of Environment, Life, Natural Sciences and Technology, Okayama University We report the synthesis and photophysical characterization of a series of “all-naphthalene” multi-chromophore systems, ternaphthalenes (TNps), designed for efficient deep-blue solid-state emission. Unlike planar polycyclic aromatic hydrocarbons that suffer from aggregation-caused quenching (ACQ), the twisted molecular architecture of TNps effectively inhibits π-π stacking interactions. Consequently, several TNps exhibit crystallization-induced emission enhancement (CIEE) or retain high quantum yields (up to 0.94) in the solid state. Kinetic analysis revealed that this efficiency stems from the significant suppression of non-radiative rates (knr) due to the restricted intramolecular rotation in the rigid crystal lattice. Furthermore, a decisive topological effect on the radiative rate (kf) was demonstrated. The 1,4-, 1,5- and 2,6-linked isomers display allowed transitions with large oscillator strengths (f) and fast radiative rate (kf = ca. 5 × 108 s−1), whereas the 2,7-linked isomers exhibit forbidden-like character with prolonged lifetimes. A distinct linear correlation between the experimental and calculated values empirically supports the applicability of the Strickler-Berg relationship in both solution and solid states. These findings demonstrate that controlling the chromophore connectivity is a powerful strategy to tune excited-state dynamics for developing high-performance deep-blue organic emitters. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2367-0932 10 3 2026 Substitution‐Dependent Modulation of Photophysical Properties of 2,7‐ and 3,6‐Dinaphthyl‐9‐phenylcarbazoles in Solution and Solid State e202500335 EN Minoru Yamaji Division of Molecular Science, Graduate School of Science and Engineering, Gunma University Tadashi Mori Research Center for Environmental Preservation and Graduate School of Engineering, The University of Osaka Hideki Okamoto Department of Chemistry, Faculty of Environment, Life, Natural Sciences and Technology, Okayama University The photophysical properties of two positional isomers of dinaphthyl-9-phenylcarbazoles (2,7-DNpPCz and 3,6-DNpPCz) were systematically investigated in solution and solid states. Experimental measurements revealed a pronounced positional dependence, although both compounds exhibit fluorescence in solution and the solid state. On average, the 2,7-isomers exhibit larger fluorescence rate values than the 3,6-isomers, although the magnitude of this difference varies among individual compounds. To gain mechanistic insight, density function theory (DFT) and time-dependence DFT calculations were performed at the (TD)-B3LYP/6-31+G(d) level. The results show that 2,7-DNpPCz derivatives possess delocalized frontier orbitals and large oscillator strengths for the S1 ← S0 transition, whereas 3,6-DNpPCz derivatives exhibit smaller oscillator strengths with mixed orbital contributions, leading to weaker transition probabilities. These combined findings demonstrate that substitution geometry critically governs radiative decay dynamics in carbazole-based luminophores and provide valuable guidelines for the molecular design of efficient solid-state organic emitters. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0016-7037 430 2026 Pervasive and rapid enrichment of nitrogen in newly erupted oceanic basalt 249 262 EN Juan Felipe Bustos-Moreno Department of Earth and Environmental Sciences, Lehigh University Tobias B. Weisenberger Geology and Sustainable Mining Institute, University Mohammed VI Polytechnic Ryoji Tanaka The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Hiroshi Kitagawa The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Gray E. Bebout Department of Earth and Environmental Sciences, Lehigh University The alteration of oceanic crust by seawater is a critical sink in the global nitrogen (N) cycle, yet the mechanisms and timescales of N enrichment remain poorly constrained. We present N concentrations and isotope compositions from a 192-meter drill core (SE-02b) retrieved from the then 50-year-old Surtsey Island in Iceland, a pristine analog for rapid alteration of young oceanic basalt. The altered basaltic tuffs show significant N enrichment (average 11 ± 8 μg/g), relative to unaltered Icelandic basalt glasses (0.028 ± 0.026 μg/g) and MORB (∼1.1 to 1.5 μg/g), matching the global average for altered oceanic crust (11 μg/g; ranging in ages from 5 to 170 Ma). Nitrogen isotope compositions (δ15Nair = −1.7 ± 4.6‰) are primarily consistent with incorporation of seawater- and meteoric-derived ammonium (NH4+), more likely into secondary K-minerals, palagonitized glass and smectites throughout the core. To a lesser extent, N could be incorporated into Na/Ca-minerals such as analcime in the meteoric water altered zone and sulphates such as anhydrite and gypsum when present. Incorporation of NH4+ into secondary phases occurs with little isotope fractionation consistent with equilibrium fractionation between clay and aqueous NH4+. We demonstrate that seawater-rock interaction alone can produce the ubiquitous background N enrichment of the oceanic crust without the addition of remobilized N from sedimentary sources. Such magnitude of enrichment is also observed via meteoric water alteration. Localized high enrichments in N in areas of enhanced fluid flow at core SE-02b with exceptionally low δ15N values (as low as −20.1‰), are attributed to abiotic reduction of dissolved N2 under anoxic conditions and/or microbial activity. We propose that N incorporation into the oceanic crust can occur rapidly in days to decades rather than at a constant rate over geologic time. This has major implications for N transfer in subduction zones, N exchange between the oceanic crust, seawater and the atmosphere and for planetary habitability. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0005-2728 1868 1 2027 Structural and functional analysis of a photosystem II mutant PsbA3-S264V 149607 EN Songbo Fan Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiki Nakajima Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koji Kato Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haowei Jiang Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Pi-Cheng Tsai Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Anqi Jia Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Miwa Sugiura Proteo-Science Research Center, Ehime University Jian-Ren Shen Advanced Research Field, Research Institute for Interdisciplinary Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Photosystem II (PSII) catalyzes water oxidation and oxygen evolution by a light-induced electron transfer chain, leading to the generation of electrons, protons and dioxygen. D1-S264 is a residue located close to the QB-binding site, and mutation of this residue has been shown to bring significant effects on the electron transfer and oxygen-evolving activities. Here we analyzed the structure of a Thermosynechococcus elongatus mutant PsbA3-S264V by cryo-electron microscopy at 1.96 Å resolution, which showed significant changes in the structure surrounding the bicarbonate and QB-binding region. Due to change of Ser to Val, the hydrogen-bond between the QB carbonyl oxygen and S264 is altered, which changed the protonation pathway of QB from the original route of D1-H252 through D1-S264 to QB, to a new, longer and less efficient route of D1-H252 through D1-F265 to QB. Two residues, D1-E244 and D2-E242, changed their side chain orientations significantly. Among them, D2-E242 adopted two conformations, and both are largely deviated from the original structure. All these changes led to alterations in hydrogen-bonding networks of two channels, channel A and channel B, that connect the stromal surface to QB and may function to transport protons to protonate QB. Furthermore, isothermal titration calorimetry experiments showed a diminished 3-(3,4-dichlorophenyl)-1, 1-dimethylurea (DCMU) binding affinity of the mutated PSII, which may be explained by a structural rotation of D1-F255 in the mutant based on structural analysis of DCMU-bound PSII. These findings offer valuable insights into the functions of D1-S264 in QB protonation and function, as well as in the DCMU-binding. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1520-541X 28 3 2026 Sexual Dimorphism in Vertebral Number: Developmental Implications Inferred From Vertebral and Body Proportions e70062 EN Kazunori Yamahira Tropical Biosphere Research Center, University of the Ryukyus V. K. Anoop Tropical Biosphere Research Center, University of the Ryukyus Rajeev Raghavan Department of Fisheries Resource Management, Kerala University of Fisheries and Ocean Studies Yoshitaka Tanaka Ushimado Marine Institute, Okayama University Satoshi Ansai Ushimado Marine Institute, Okayama University Segmentation is a fundamental feature of vertebrate body plans, and variation in vertebral number contributes substantially to morphological diversity. Although sexual dimorphism in vertebral number has been documented in several vertebrate lineages, its developmental basis remains poorly understood. Here, we report pronounced sexual dimorphism in vertebral number in the western Indian endemic ricefish Oryzias setnai, distributed across ~1800 km. Radiographic analyses of individuals collected throughout its range revealed that vertebral number increased with latitude in both sexes, while males consistently possessed more vertebrae than females irrespective of geographic origin. Size-adjusted analyses showed that this dimorphism is associated with sex differences in head size and position-dependent variation in vertebral length. However, positional allometric analyses demonstrated that both the magnitude and direction of these sex differences vary markedly during growth. In particular, among smaller individuals, posterior vertebrae were relatively shorter in males than in females, suggesting reduced somite length in the posterior body axis of male embryos and potentially reflecting sex-specific differences in the dynamics of somitogenesis. Given that this variation arises between males and females within a single species sharing an essentially identical genetic background, O. setnai provides a rare empirical system not only for linking early developmental processes to intraspecific sexual variation in vertebrate body plans but also as a powerful model to investigate the developmental basis of body plan variation across species. No potential conflict of interest relevant to this article was reported.

日本健康教育学会 Acta Medica Okayama 1340-2560 34 2 2026 中・高・大学生の健診結果活用の促進要因―ヘルスリテラシースキルフレームワークを用いた検討― 118 129 EN Hitomi ONISHI The Joint Graduate School (Ph.D. Program) in Science of School Education, Hyogo University of Teacher Education Nobuki NISHIOKA Faculty of Psychology and Collaboration, Kyoto Women’s University Takehiko ITO Graduate School of Education, Okayama University 目的：学校健康診断結果活用（以下，活用）と関連要因及び相互の関連性をヘルスリテラシースキルフレームワークを用いて明らかにすることを目的とした．<br> 方法：中学生493名，高校生360名，大学1年生297名を対象に無記名自記式質問紙調査を行った．調査内容は活用と，健康への関心，ヘルスリテラシー（以下，HL），健診結果に対する認識，健診結果の読解力（以下，読解力），意思決定バランスとした．これらの関連性を示す仮説モデルを校種，性別の多母集団同時パス解析で検証した．<br> 結果：仮説モデルに4つのパスを追加した修正モデルで，校種，性別いずれにおいても配置不変モデルで良好な適合度を得た．健診結果に対する認識から読解力，読解力から意思決定バランス，意思決定バランスから活用，健康への関心から読解力，意思決定バランス，活用へのパス及び，HLから活用へのパスは全ての校種において有意であった．健康への関心と結果に対する認識からHL，HLから読解力，意思決定バランスへのパスは中・高校生のみで有意であった．<br> 結論：中・高・大学生の健診結果活用を促すためには，健診結果を分かりやすくすること，健診結果の読解力及び意思決定バランスの向上，すなわち恩恵の認識の向上と，負担の認識の軽減が有効であり，その際に対象者の健康への関心とHLの程度を考慮する必要性が示唆された． No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 2026 Clinical outcomes of near-infrared photoimmunotherapy according to immune checkpoint inhibitor timing and treatment sequence: a multicenter retrospective study EN Takuma Makino Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shohei Fujimoto Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yorihisa Orita Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kumamoto University Tomoyasu Tachibana Department of Otolaryngology Head and Neck Surgery, Japanese Red Cross Society Himeji Hospital Yuto Naoi Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mizuo Ando Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Near-infrared photoimmunotherapy (NIR-PIT) is a novel local treatment for recurrent or metastatic head and neck cancer. However, the clinical significance of immune checkpoint inhibitor (ICI) timing and treatment sequencing remains unclear. This study investigated their association with clinical outcomes after NIR-PIT.<br> Methods This multicenter retrospective study included 44 patients with 48 lesions who underwent initial NIR-PIT between January 2021 and March 2026. The primary analysis compared outcomes according to prior ICI exposure. An exploratory analysis evaluated outcomes according to treatment sequence and timing of ICI administration. The primary endpoint was local control. Secondary endpoints were objective response rate and disease control rate, while overall survival was assessed exploratorily.<br> Results Median local control duration was 253 days, but was 174 days in the prior ICI exposure group and 342 days in the non-prior ICI exposure group (log-rank P = 0.031). Local progression occurred in 69.2–37.1% of lesions, respectively (P = 0.059). Among 45 evaluable lesions, the objective response rate and disease control rate were 60.0–93.3%, respectively. Median overall survival was 866 days. Exploratory analyses suggested potential differences in clinical outcomes according to treatment sequence and ICI timing.<br> Conclusions Prior ICI exposure was associated with poorer local control after NIR-PIT. Exploratory analyses suggested that ICI timing and treatment sequencing may influence clinical outcomes. Treatment sequencing may represent an important consideration when integrating NIR-PIT and ICIs for recurrent or metastatic head and neck cancer. No potential conflict of interest relevant to this article was reported.

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 49 6 2026 Effect of Deuterated Drugs on Safety: Insights from Pharmacovigilance Data Analysis 983 988 EN Kohei Kitagawa Department of Neuropsychiatry, Okayama Psychiatric Medical Center Hideki Nawa Department of Pharmacy, Faculty of Pharmacy, Shujitsu University Shota Asai Department of Pharmacy, Faculty of Pharmacy, Shujitsu University Naohiro Iwata Department of Pharmacy, Okayama University Hospital Takahiro Niimura Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Mitsuhiro Goda Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Keisuke Ishizawa Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Huntington’s disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. Tetrabenazine (TBZ), a vesicular monoamine transporter 2 inhibitor, is commonly used to manage chorea; however, it may exhibit fluctuating plasma levels and elicit frequent adverse events. In this study, we aimed to clarify the effects of TBZ deuteration on its safety profile. We compared the safety profiles of TBZ and deutetrabenazine (DTBZ) in real-world clinical practice using disproportionality analysis and the large-scale pharmacovigilance database, VigiBase―the WHO’s global database of adverse drug reactions. Adverse event signals were assessed using the information component (IC). Seriousness was classified according to clinical outcome, and time to onset (TTO) was analyzed for selected events. TBZ showed signals for disorientation, dystonia, and sleep disorders (IC025 > 0), whereas DTBZ did not. Serious adverse events were reported in 54.7% of TBZ cases and 37.9% of DTBZ cases. The TTO of sleep disorder was also evaluated; however, the number of cases with available TTO information was limited. DTBZ showed fewer adverse event signals and a lower proportion of serious adverse events than TBZ. These findings suggest potential differences in the safety profiles of the two drugs, which may influence tolerability in the treatment of HD. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 2045-1253 16 2026 Seizures associated with clozapine augmentation by other antipsychotics: a pharmacovigilance–pharmacodynamic analysis using VigiBase EN Masakazu Hatano Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Masaya Kanda Department of Pharmacy, Asahikawa Medical University Hospital Takenao Koseki Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine Tsuyoshi Nakai Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine Rina Horii Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine Nozomi Yoshihara Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine Takeo Saito Department of Psychiatry, Fujita Health University School of Medicine Kenshi Takechi Department of Drug Information Analysis, College of Pharmaceutical Sciences, Matsuyama University Satoru Esumi The Faculty of Pharmaceutical Sciences, Kobe Gakuin University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Shigeki Yamada Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine Background: Clozapine is associated with a high risk of central nervous system abnormalities. However, seizure risk related to interactions between clozapine and other antipsychotics remains poorly characterized, and the pharmacological mechanisms underlying these seizures are unclear. Objectives: We aimed to evaluate safety signals for seizures associated with clozapine augmentation by other antipsychotics and analyze the relationship between these signals and neurotransmitter receptor occupancy profiles.<br> Design: A pharmacovigilance–pharmacodynamic analysis using a spontaneous reporting system.<br> Methods: This pharmacovigilance study used VigiBase, an adverse drug reaction database maintained by the World Health Organization. Drug–drug interactions (DDIs) between clozapine and other antipsychotics were assessed using the Ω shrinkage measure model. The association between DDI signals and neurotransmitter receptor occupancy was evaluated using linear regression. Robustness was tested using four frequency statistical models: additive, multiplicative, combination risk ratio, and chi-square statistic models. Results: Of 38,758,077 reports in VigiBase between 1990 and 2024, 230,371 involved clozapine. Among antipsychotics classified under ATC code N05A, DDIs with clozapine were detected for amisulpride, chlorpromazine, haloperidol, lurasidone, olanzapine, penfluridol, risperidone, sulpiride, zotepine, and zuclopenthixol. A significant association between dopamine D4 receptor occupancy and the point estimates of signal values was observed in the Ω shrinkage measure model (β = 0.295, 95% confidence interval: 0.119–0.471, p = 0.002) and replicated across all frequency statistical models.<br> Conclusions: These findings suggest a potential role of dopamine D4 receptor occupancy in seizures associated with clozapine augmentation by other antipsychotics. Further large-scale epidemiological studies are needed to validate these findings. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1477-0520 2026 Stereoselective synthesis of β,β-diborylalanine (AlaBB) and its incorporation into oligopeptides EN Naoyuki Nitta Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kenshin Nakai Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haruki Mizoguchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Akira Sakakura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University We report the stereoselective synthesis of β,β-diborylalanine (AlaBB), a compact amino acid scaffold designed to introduce a gem-diboronic acid motif as a branched connector in peptides. Pinacol-protected AlaBB derivatives, denoted as AlaBB(pin)2, were prepared from an Ellman imine, incorporated into short peptides, and converted to the corresponding gem-diboronic acid form. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2475-0328 2026 Biological Resectability in Colorectal Liver Metastases: A Nomogram‐Based Continuous Risk Model to Define Borderline Disease EN Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Kojima Department of Surgery, Okayama Saiseikai General Hospital Takeshi Koujima Department of Surgery, Himeji Red Cross Hospital Tatsuo Matsuda Department of Surgery, Tenwakai Matsuda Hospital Daisuke Satoh Department of Surgery, Hiroshima Citizens Hospital Masaru Inagaki Department of Surgery, National Hospital Organization Fukuyama Medical Center Kosei Takagi 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: Resectability in colorectal liver metastases (CRLM) is traditionally defined by technical feasibility; however, a biologically based definition of borderline resectable disease has not been established. We evaluated the prognostic impact of KRAS mutation and developed a model for biological risk stratification.<br> Methods: This multi-institutional retrospective study included 584 patients undergoing initial hepatectomy for CRLM. The impact of KRAS mutation was assessed according to primary tumor sidedness and tumor burden score (TBS). A nomogram predicting overall survival (OS) was constructed using independent prognostic factors and compared with established clinical risk scores.<br> Results: KRAS mutation was identified in 36.8% of patients and was associated with worse OS (median survival: 47.3 vs. 70.6 months, p = 0.0006) and recurrence-free survival. This adverse impact was observed in left-sided tumors but not in right-sided tumors. TBS stratified prognosis in KRAS wild-type but not in mutant cases, suggesting that tumor biology may outweigh morphology. A nomogram incorporating KRAS status, TBS, CA19-9, primary nodal status, and extrahepatic disease demonstrated improved discriminatory ability compared with conventional models and stratified recurrence patterns, including extrahepatic recurrence.<br> Conclusions: The prognostic impact of KRAS mutation depends on tumor sidedness and is independent of tumor morphology. Our nomogram provides a continuous biological risk assessment and may facilitate biological risk stratification and support future refinement of the concept of biologically borderline resectable CRLM. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 2165-0497 14 8 2026 High-throughput screening system for antimycobacterial compounds using in vitro infected cells: construction and application to compounds in the Ōmura Natural Compound Library e00484-26 EN Takemasa Takii Department of Mycobacterium Reference and Research, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association Aoi Kimishima Ōmura Satoshi Memorial Institute, Kitasato University Masato Iwatsuki Ōmura Satoshi Memorial Institute, Kitasato University Yoshihiro Watanabe Ōmura Satoshi Memorial Institute, Kitasato University Naoya Ohara Department of Oral Microbiology, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University Yukihiro Asami Ōmura Satoshi Memorial Institute, Kitasato University The global increase in multidrug-resistant tuberculosis strains poses a major threat; consequently, there is an urgent need to identify and develop novel drugs. We have previously presented a simple fibroblast assay (SFA) screening method that enables the simultaneous assessment of antibacterial activity and cytotoxicity toward host cells. This method was developed based on our finding that live (but not dead) Mycobacterium tuberculosis bacilli exhibit cytotoxic activity against human lung fibroblasts, and that this cytotoxicity, which is proportional to the number of viable bacterial cells, is inhibited by known antimycobacterial drugs. While conventional methods to measure M. tuberculosis growth require 2–4 weeks to detect antibacterial activity; the SFA method enables detection within 2–3 days and can detect compounds that are active within host cells. Here, we applied high-throughput screening, based on assessment of cytotoxicity, to identify candidate antimycobacterial agents. In parallel, by comparing the direct antibacterial activity of compounds in liquid medium (using the broth dilution test) with that observed via SFA, we developed a new SFA-based screening system to select compounds with low cytotoxicity that are active outside or inside the host cells. Using this dual system, we screened 742 compounds from the Ōmura Natural Compound Library (Kitasato University, Japan), with 62 hits. Of these, 19 were excluded owing to their toxicity, and six exhibited antibacterial activity only via SFA screening. Four promising antimycobacterial candidates with no cytotoxicity at the 10 μg/mL threshold―aridicin A, lankamycin, streptovaricin, and lariatin A―were identified. identified.This novel system supports the rapid identification of low-cytotoxicity antimycobacterial compounds that are active inside or outside the host cells. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1477-0520 2026 Stereoselective synthesis of β,β-diborylalanine (AlaBB) and its incorporation into oligopeptides EN Naoyuki Nitta Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kenshin Nakai Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haruki Mizoguchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Akira Sakakura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University We report the stereoselective synthesis of β,β-diborylalanine (AlaBB), a compact amino acid scaffold designed to introduce a gem-diboronic acid motif as a branched connector in peptides. Pinacol-protected AlaBB derivatives, denoted as AlaBB(pin)2, were prepared from an Ellman imine, incorporated into short peptides, and converted to the corresponding gem-diboronic acid form. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2590-1230 32 2026 Prediction of tool-path and cycle time errors of CNC machining using a transformer-based deep learning model 112872 EN Kazuki Kaneko Graduate School of Environmental, Life, Natural Science and Tech, Okayama University Zongze Li Graduate School of Advanced Science and Engineering, Hiroshima University The prediction of tool-path and cycle time errors of computer numerical control (CNC) machining is important in manufacturing field. In this study, these errors are considered as sequential data corresponding to the lines of G-code, i.e., the error prediction is a sequence-to-sequence task, and a Transformer-based deep learning model was constructed to predict the tool-path and cycle time errors simultaneously, taking the positional increments and feed rate as the input. The training datasets were created by running a randomly generated G-code on a real CNC machine tool and subsequently tracking the actual errors, where the motion and feed rate are stochastically defined. The model is validated by conducting the error prediction on six sets of G-code. In addition, the comparison with a Bi-LSTM-based deep learning model is conducted. The results show that the prediction accuracy of the Transformer model can achieve the mean prediction accuracies of ±1 μm and ±1 ms in tool-path and cycle time error predictions, respectively. Furthermore, the Transformer model has a smaller prediction uncertainty than the Bi-LSTM model. Compared with conventional methods only analyzing tool-path errors or cycle-time errors, the utilized model has an advantage in its ability to simultaneously predict tool-path errors and cycle time errors. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1880-6546 76 3 2026 Effects of serotonin transporters on myocardial cell injury during ischemia/reperfusion in rats 100085 EN Yoshimasa Kishi Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Shuji Shimizu Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Yosuke Kuroko 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 Tsuyoshi Akiyama Department of Cardiac Physiology, 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 Serotonin (5-HT) reuptake in the heart is mediated by the platelet serotonin reuptake transporter (SERT) and the cardiomyocyte plasma membrane monoamine transporter (PMAT). However, the specific roles of these transporters in myocardial cell injury during ischemia/reperfusion remain unclear. Sprague-Dawley rats underwent left coronary artery occlusion followed by reperfusion. Using cardiac microdialysis technique, fluoxetine (SERT inhibitor, 900 μM) or decynium 22 (PMAT inhibitor, 100 μM) was administered locally to the ischemic region. Myoglobin concentrations in the dialysate were measured during ischemia followed by reperfusion. In the fluoxetine-treated group, peak myoglobin concentration (14,889 ± 1364 ng/mL) during 0–15 min of reperfusion was significantly higher compared to both the control group (9800 ± 1627 ng/mL) and the decynium 22-treated group (8172 ± 877 ng/mL) (P < 0.01 for both). Local SERT inhibition exacerbated myocardial cell injury during ischemia/reperfusion. However, co-inhibition of PMAT reduced myocardial cell injury under SERT inhibition to the control level. No potential conflict of interest relevant to this article was reported.

American Astronomical Society Acta Medica Okayama 0004-637X 999 2 2026 Constraining the Effects of Pre- and Post-accretionary Processes on Ryugu Insoluble Organic Matter 187 EN Christian Potiszil Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Masahiro Yamanaka Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Tsutomu Ota Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Chie Sakaguchi Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Hiroshi Kitagawa Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Ryoji Tanaka Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Tak Kunihiro Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Katsura Kobayashi Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Eizo Nakamura Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Asteroidal and cometary fragments have been indicated as possible sources of the building blocks of life for the early Earth. Samples returned from the asteroid Ryugu are uncontaminated and contain organic matter. Such samples enable an investigation of the processes that formed and altered extraterrestrial organic matter. Here, the FTIR and Raman responses of insoluble organic matter (IOM) isolated from Ryugu particles and carbonaceous chondrites are reported. Several relationships were observed: (1) a strong positive correlation of CH2/CH3 plotted against aliphatics/C=C; (2) a strong negative correlation of CH2/CH3 plotted against δ15N and δ13C; and (3) strong negative correlations of FTIR band ratios plotted against Raman band parameters and D/G values. The data are not consistent with even moderate heating of the IOM, as indicated by CH2/CH3 ratios that are consistent with unheated carbonaceous chondrites. The C and N isotope data previously collected for each Ryugu particle preclude aqueous alteration based on our understanding of its effects on carbonaceous chondrite IOM. Mixing of several IOM endmembers was considered, but due to the similarities of the particle with the lowest CH2/CH3 ratio to the other particles in terms of its other spectroscopic parameters, this scenario was considered unlikely. Finally, the effects of irradiation were considered, and UV irradiation, in particular, was hypothesised to be the best explanation for the trends observed. Overall, the data highlight the importance of comprehensive data sets for revealing extraterrestrial processes, which could define the nature of organic matter reaching habitable environments, such as those of the Early Earth. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 0094-8276 53 13 2026 Limits of Water Storage in Stishovite at Deep Mantle Conditions e2025GL120078 EN Fei Wang Bayerisches Geoinstitut, University of Bayreuth Artem Chanyshev Bayerisches Geoinstitut, University of Bayreuth Lianjie Man Bayerisches Geoinstitut, University of Bayreuth Yunke Song Bayerisches Geoinstitut, University of Bayreuth Lin Wang Bayerisches Geoinstitut, University of Bayreuth Takayuki Ishii Institute for Planetary Materials, Okayama University Noriyoshi Tsujino Japan Synchrotron Radiation Research Institute Shrikant Bhat Deutsches Elektronen‐Synchrotron DESY Robert Farla Deutsches Elektronen‐Synchrotron DESY Tomoo Katsura Bayerisches Geoinstitut, University of Bayreuth The deep Earth water cycle is a key process in Earth's evolution. Stishovite has been proposed as a major carrier of water from the surface into the lower mantle. However, its role remains unclear because its water solubility is controversial. We investigated the water solubility of Al-free stishovite at pressures of 33–38 GPa and temperatures of 700–1200 K using in situ X-ray diffraction in an advanced multianvil apparatus. Water solubility is high, around 3 wt%, at 700 K but decreases rapidly with increasing temperature and becomes negligible (<1,000 ppm), at temperatures above 1000 K. These results suggest that pure stishovite is unlikely to transport significant amounts of water into Earth's lower mantle under comparable pressure-temperature conditions. Previously reported high water contents in pure stishovite under deep Earth conditions likely reflect the solubility of post-stishovite or experimental artifacts. 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 Cold SiO2-rich slabs reaching the CMB revealed by the seifertite phase boundary 26394 EN Ryosuke Sinmyo Department of Physics, School of Science and Technology, Meiji University Saori Kawaguchi-Imada Japan Synchrotron Radiation Research Institute Rei Sato Department of Earth and Planetary Science, School of Science, The University of Tokyo Keisuke Otsuru Japan Synchrotron Radiation Research Institute Kenji Kawai Japan Synchrotron Radiation Research Institute Hiroshi Sakuma Environmental Circulation Composite Materials Group, National Institute for Materials Science Shigeru Suehara Environmental Circulation Composite Materials Group, National Institute for Materials Science Takayuki Ishii Institute for Planetary Materials, Okayama University Shuhou Maitani Department of Physics, School of Science and Technology, Meiji University A cold silica (SiO2)-rich subducted slab creates notable heterogeneity above the core-mantle boundary (CMB), influencing the evolution of the Earth’s mantle. This slab may exhibit characteristic anomalies in the longitudinal and shear wave seismic velocity above the CMB, attributed to the SiO2 phase transition into its dense polymorph, seifertite. However, the transition depth remains unclear due to the often-observed metastable phases in experiments. To address this long-standing challenge, we conducted laser-heated diamond anvil cell experiments with synchronised rapid X-ray diffraction measurements alongside theoretical calculations. The slope of the seifertite phase boundary was less steep than previously estimated, and consequently, the temperature profile of the slab crosses the boundary twice, like the post-perovskite transition. We observed a decrease in shear wave velocity beneath Hawaii and Central America, and we found anti-correlation in seismic wave velocities matching the depth range of the seifertite transition in a cold slab beneath Central America. This may provide evidence that a cold SiO2-rich slab descends towards the CMB. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2667-2421 19 2025 Chronic fluoxetine modulates perineuronal nets and inhibitory neuronal function in relation to behavioral outcomes 781 791 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Eriko Kitano Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Chronic fluoxetine administration has been reported to enhance neural plasticity in the adult brain, but the underlying structural correlates remain incompletely understood. In particular, the impact of fluoxetine on aggrecan-positive perineuronal nets (PNNs)―critical regulators of plasticity―is largely unknown. We investigated whether chronic fluoxetine treatment (20 mg/kg/day, i.p., 21 days) alters behavior and PNN expression in adult male C57BL/6 N mice. Behavioral assessments included grip strength, hot plate, light/dark transition, elevated plus-maze, open field, Y-maze, social interaction, tail suspension, Porsolt forced swim, and passive avoidance tests. To evaluate structural plasticity, we performed immunohistochemical analyses of parvalbumin (PV)-positive neurons and PNNs using aggrecan-specific antibodies (Cat-315, AB1031) in the primary somatosensory cortex and hippocampus. Fluoxetine-treated mice exhibited increased exploration and reduced anxiety-like behavior in light/dark transition and elevated plus-maze tests, with no significant changes in grip strength or nociception. They also showed increased locomotor activity (distance and entries) in the Y-maze, but did not significantly alter spontaneous alternation performance, and increased social interaction, the latter possibly reflecting abnormal social behavior. No significant differences were observed in depression-like behavior as assessed by tail suspension and forced swim tests. Passive avoidance performance was impaired, suggesting a decline in cognitive function. Immunohistochemical analysis revealed a significant reduction in aggrecan-positive PNN density, particularly in layer 4 of the primary somatosensory cortex and in the CA1 and CA3 regions of the hippocampus. Our results indicate that chronic fluoxetine administration induces behavioral and structural changes indicative of reactivated neuroplasticity. Importantly, these changes are associated with a region- and layer-specific reduction of aggrecan-positive PNNs, underscoring their critical role in modulating adult cortical plasticity. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0953-8194 38 9 2026 Marine flatworms as windows into the evolution of bilaterian neuropeptide signalling e70259 EN Ryo Nakamura Ushimado Marine Institute, Faculty of Science, Okayama University Mayuko Hamada Ushimado Marine Institute, Faculty of Science, Okayama University Xavier Bailly Multicellular Marine Models Team, CNRS – Sorbonne University – Station Biologique de Roscoff Hirotaka Sakamoto Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Tatsuya Sakamoto Ushimado Marine Institute, Faculty of Science, Okayama University The evolutionary origin(s) of neuropeptide signalling is still largely unknown. It has been hypothesised that signal transmission via neuropeptides played a crucial role in the regulation of nervous systems in the bilaterian ancestor. Identification, expression and functional analyses of neuropeptides and their receptors across different taxonomic groups are important for better understanding the origin(s) of bilaterian neuropeptide signalling. An example is flatworms belonging to the Platyhelminthes (spiralian protostomes) and Xenacoelomorpha (sister to all Bilateria or sister to Ambulacraria). Despite their simple morphology (i.e., a body plan lacking a coelom and circulatory system), they often possess brain-like central nervous systems and a number of bilaterian-conserved neuropeptides. This feature makes them useful models for analyses of neuropeptides and their links to nervous systems. Although previous studies have revealed orthologous relationships between vertebrate neuropeptides and those found in both marine Platyhelminthes and Xenacoelomorpha, our work suggests possible ancestral functions of vasopressin/oxytocin (VP/OT) peptides (platytocin) in these groups. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0009-2541 713 2026 Tungsten(VI) speciation in aqueous fluids at high pressures and high temperatures: in-situ Raman spectroscopy supported by DFT calculations 123411 EN Naoko Takahashi Department of Earth Science, Graduate School of Science, Tohoku University Michihiko Nakamura Department of Earth Science, Graduate School of Science, Tohoku University Shigeru Yamashita Institute for Planetary Materials, Okayama University Hiroyuki Kagi Geochemical Research Center, Graduate School of Science, The University of Tokyo Tungsten (W) is mobile in magmatic–hydrothermal and deep subduction zone fluids, and its stable isotopes offer potential as tracers of fluid-rock interactions. We investigated W behavior in aqueous fluids using in-situ Raman spectroscopy on slightly acidic to alkaline Na2WO4 solutions (10−3–10−1 M W) and WO3–H2O/D2O ± NaCl systems up to 1.4 GPa and ∼800 °C, with the band assignments supported by density functional theory (DFT) calculations. Raman spectra showed that the ν1 mode of WO42− persisted to the highest P–T conditions in alkaline fluids, while additional high-frequency bands near 950 or 973 cm−1 appeared at elevated T in the studied fluids. Their relative intensities depended on T, pH, and NaCl content; the 973 cm−1 band was only observed above 650 °C in Na-free fluids. Substitution of H2O with D2O did not significantly affect the band frequencies. Based on analogous molybdenum experiments, previous in-situ studies, and thermodynamic models, these high-T bands are assigned to mononuclear species rather than polynuclear species, consistent with the stepwise formation of hydrogentungstate anion, HWO4−, and then neutral tungstic acid, H2WO4, as T increases. DFT vibrational frequency calculations for HWO4−, H2WO4, and their D-substituted species support this interpretation, suggesting tetrahedral HWO4− and higher-coordinated H2WO4 as plausible species. The present study clarifies Raman band assignments for HWO4− and paratungstate A (W7O246−) to address previous ambiguities in the literature, and confirms that polynuclear species play a negligible role in high-T ore-forming fluids. The tetrahedral HWO4− appears to be a predominant transport species in NaCl-bearing metamorphic fluids and may govern stable W isotope fractionation during deep fluid-rock interactions. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1738-5733 59 1 2027 Impact of correcting beam hardening and detector response function in photon-counting X-ray imaging when using anti-coincidence mode 104678 EN Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Daiki Kobayashi Graduate School of Medical Sciences, Kanazawa University Takuya Kasue Graduate School of Medical Sciences, Kanazawa University Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University X-ray imaging using photon-counting detectors (PCDs) allows for the calculation of quantitative images such as the effective atomic number (𝑍eff). However, physical phenomena such as characteristic X-ray emission and charge sharing can cause incomplete total absorption events during signal generation, which reduces the accuracy of X-ray penetration analysis. To solve the problem, an anti-coincidence mode (ACM) has been developed, but complete correction has not been established. We aimed to investigate the accuracy of 𝑍eff image when the proposed software-based corrections, namely beam hardening and response function corrections, are added to the hardware-based correction of the ACM. The response function was calculated using the Monte-Carlo simulation code. In a simulation study, we analyzed a phantom composed of virtual materials with 𝑍eff values of 4–16. While sufficient accuracy cannot be achieved by applying only the ACM, it was demonstrated that low-noise 𝑍eff images can be obtained by applying our correction. Furthermore, it was demonstrated that 𝑍eff images of food samples can be generated by using actual non-destructive testing equipment with a 10 m/min transportation speed. In conclusion, our correction procedure can maximize the performance of PCDs, and our findings are essential for promoting imaging techniques concerning quantitative images. No potential conflict of interest relevant to this article was reported.

Ceramic Society of Japan Acta Medica Okayama 1348-6535 134 9 2026 Preparation of chitosan/apatite composite particles with core–shell structure 676 681 EN Takuya Kataoka Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ryo Ikeda Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Eiji Fujii Industrial Technology Center of Okayama Prefecture Tomohiko Yoshioka Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Satoshi Hayakawa Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University In this study, a novel sequential preparation process of core–shell particles with chitosan (CS) cores and hydroxyapatite (HAp) shells is presented. This process involved the formation of phosphorylated CS particles, followed by HAp precipitation. Importantly, the precipitation of HAp on the surface of phosphorylated CS was confirmed. Different CaCl2 concentrations during the HAp precipitation step resulted in different HAp contents in the particles. To confirm the formation of the core–shell structure, the particles were immersed in hydrochloric acid (pH 2) for 5, 10, and 30 min. Notably, samples with higher HAp content (59 wt % and 84 wt %) retained their core morphology after 30 min of immersion, whereas samples with lower HAp content (28 wt %) rapidly lost their morphology. These results indicate that higher HAp content contributes to improved morphological stability under acidic conditions, leading to the formation of more stable core–shell particles. Overall, these findings clarify the role of phosphorylated CS in inducing HAp precipitation and show that the proposed preparation process leads to the formation of CS/HAp core–shell structures. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2041-1723 17 1 2026 Water exchange process and bulk composition regulate slab dynamics and deep earthquakes 8291 EN Jintao Zhu Institute for Planetary Materials, Okayama University Renbiao Tao Center for High Pressure Science and Technology Advanced Research (HPSTAR) Lifei Zhang SKLab-DeepMinE, MOEKLab-OBCE, School of Earth and Space Sciences, Peking University Takayuki Ishii Institute for Planetary Materials, Okayama University Water strongly influences deep mantle processes, including geochemical cycles, slab dynamics, and deep-focus earthquakes. Yet the stability and interactions of hydrous minerals with nominally anhydrous minerals (NAMs) under the water-undersaturated conditions of subducting slabs remain unclear. Here we show, using high-pressure and high-temperature experiments on MgO–SiO2–H2O systems (~2 wt% H2O), that hydrous minerals progressively dehydrate in the mantle transition zone, transferring water to NAMs such as wadsleyite and ringwoodite, while the cold slab core stays nearly dry. Rapid dehydration near the top of the lower mantle may generate fluids linked to the deepest earthquakes. Our results indicate that dry olivine transformations, rather than dehydration embrittlement, likely trigger most deep-focus earthquakes, and that hydration variations in NAMs influence slab deformation and stagnation above 660 km. The bulk Mg/Si ratio controls hydrous mineral stability, suggesting harzburgite transports water more efficiently than peridotite. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2198-4034 12 1 2026 Development of a preoperative accuracy prediction model using machine learning for implant placement in static-guided surgery: retrospective observational study 44 EN Takuya Mino Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University Yurina Matsuoka Department of Semiconductor, Computer Science and Applied Mathematics, Graduate School of Science and Technology, Kumamoto University Ken’ichi Morooka Division of Biomedical Engineering, Faculty of Advanced Science and Technology, Kumamoto University Kana Tokumoto Department of Oral and Maxillofacial Surgery, School of Medicine, Hyogo Medical University Hiroaki Shimizu Shimizu Dental Clinic Yoko Kurosaki Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University Aya Kimura-Ono Center for Innovative Clinical Medicine, Okayama University Hospital Hiromitsu Kishimoto Department of Oral and Maxillofacial Surgery, School of Medicine, Hyogo Medical University Takuo Kuboki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kenji Maekawa Department of Removable Prosthodontics and Occlusion, School of Dentistry, Osaka Dental University Purpose This study aimed to develop a machine learning model capable of preoperatively predicting three-dimensional implant placement errors at the implant apex in static-guided surgery and to identify the clinical features associated with placement accuracy.<br> Methods Clinical data partially derived from a previous observational study were analyzed. In total, 181 patients and 480 implants placed using fully static-guided surgery were included in this study. The outcome variable was defined as three-dimensional implant placement error at the implant apex relative to the preoperative simulation, dichotomized as less than 0.5 mm or ≥ 0.5 mm. Twenty-one clinical and radiographic factors previously suggested to influence the placement accuracy were used as explanatory variables. The feature importance was evaluated using three gradient boosting decision tree models. Furthermore, a stacking model combining multiple classifiers was constructed, and the classification performance was assessed using ten-fold cross-validation.<br> Results The feature importance analysis identified 12 features associated with implant placement errors. The stacking model demonstrated superior classification performance compared to individual classifiers. The true positive rate was 0.73, false negative rate was 0.27, false positive rate was 0.14, and true negative rate was 0.86.<br> Conclusions The proposed stacking model correctly classified 86% of cases with implant placement error less than 0.5 mm and 73% of cases with implant placement error of ≥ 0.5 mm. These findings suggest that the proposed model may support the preoperative evaluation of implant placement accuracy in static-guided surgeries. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2075-4418 16 17 2026 Granular Swollen Epithelial Cells in Native Kidney Biopsies: Prevalence, Clinicopathological Associations and Kidney Outcomes 2822 EN Naruhiko Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kitamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Objectives: Granular swollen epithelial cells (GSECs) have been described primarily in mitochondrial cytopathies, in which they are regarded as a characteristic pathological finding that may aid in the diagnosis of mitochondrial dysfunction; however, their prevalence and clinical significance in native kidney disease remain unclear. We aimed to evaluate the prevalence, clinicopathological associations, and prognostic significance of GSECs in native kidney biopsy specimens. Methods: Among 1165 adults who underwent native kidney biopsy between 2011 and 2024, 501 patients with evaluable medullary tissue were included in this retrospective cohort study. GSECs were defined as enlarged tubular epithelial cells with conspicuous granular cytoplasm in medullary tubules, and cases were classified as GSEC-positive when at least one unequivocal GSEC was identified. Clinical and histopathological characteristics were compared between groups, and kidney outcomes were evaluated using Cox proportional hazards models. Results: The mean baseline eGFR was 60.8 ± 26.3 mL/min/1.73 m2, and the median urinary protein excretion was 1.1 g/gCr. During a median follow-up of 2.3 years, 112 patients (22.3%) reached the composite kidney outcome. GSECs were identified in 18% of native kidney biopsy specimens containing evaluable medullary tissue, and were observed across a broad spectrum of kidney diseases. GSEC positivity was associated with older age and underlying pathological diagnoses but was not associated with baseline kidney function or proteinuria. Kaplan–Meier and multivariable Cox analyses revealed no significant association between GSECs and kidney prognosis. Conclusions: GSECs are not specific to kidney allografts and are observed in a subset of diverse native kidney diseases. Although associated with certain clinical characteristics, no independent association between GSECs and kidney outcomes was observed in this cohort. These findings suggest that GSECs may reflect disease-dependent biological responses to tubular epithelial stress, potentially related to metabolic or mitochondrial alterations, rather than a marker of progressive kidney injury. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2212-8778 112 2026 Adaptive oligodendrogenesis regulates blood-hypothalamus barrier permeability, hypothalamic glucose sensing and systemic glucose homeostasis in male mice 102428 EN Sophie Buller Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Emily O. Staricoff Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Christine Riches Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Anthony Tsang Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Giada Giavara Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Masa Josipovic Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Kentaro Ikemura Department of Medical Technology, Graduate School of Health Sciences, Okayama University Gabriel Opoku Department of Medical Technology, Graduate School of Health Sciences, Okayama University Ikumi Sato Department of Medical Technology, Graduate School of Health Sciences, Okayama University Satoshi Hirohata Department of Medical Technology, Graduate School of Health Sciences, Okayama University Saskia Stenzel Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Stuart G. Nayar Wolfson Institute for Biomedical Research, University College London Marta Ramos Vega GUBRA Jacob Hecksher-Sørensen GUBRA Sebastian Timmler Cambridge Stem Cell Institute, University of Cambridge Georgina K.C. Dowsett Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Brian Y.H. Lam Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Giles S.H. Yeo Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Kimberly M. Alonge Diabetes Institute, University of Washington Huiliang Li Wolfson Institute for Biomedical Research, University College London William D. Richardson Wolfson Institute for Biomedical Research, University College London Mark L. Evans Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Clemence Blouet Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Objective: Brain glucose sensing is critical for survival during hypoglycaemia, yet how glucose-sensing neurons access circulating glucose concentrations to maintain glucose homeostasis remains poorly understood. Here we tested the hypothesis that adult oligodendrogenesis in the median eminence (ME) is responsive to changes in blood glucose levels and contributes to hypothalamic glucose sensing through regulation of the blood-hypothalamus barrier.<br> Methods: We used glycemic challenges and hypoinsulinaemic clamp studies to identify the effect of systemic changes in glycaemia on hypothalamic oligodendrocyte lineage cells. We used conditional knockout mouse models to dissect the respective contributions of adult oligodendrogenesis and new myelin formation to glucose homeostasis in adult male mice. Analyses combined immunofluorescence, serial electron microscopy, whole-brain tissue clearing, and transcriptomic analyses.<br> Results: We found that adult oligodendrogenesis in the median eminence (ME) is modulated by changes in circulating glucose levels and rapidly upregulated by hypoglycaemia. Genetic blockade of new oligodendrocyte production in adult male mice impairs the regulation of glucose homeostasis, the integrity of the ME blood-hypothalamus barrier, and hypothalamic glucose sensing. Unexpectedly, functional integrity of adult-formed myelin is not required for the maintenance of glucose homeostasis. Instead, we show that blockade of adult oligodendrogenesis disrupts hypothalamic expression of A disintegrin and metallopeptidase with thrombospondin motifs 4 (ADAMTS4), a metallopeptidase whose brain expression is restricted to the oligodendrocyte lineage and whose ME expression requires ongoing adult oligodendrogenesis. We show that ADAMTS4 regulates hypothalamic perineuronal net deposition, vascular permeability and glucose sensing. Finally, we show that ME ADAMTS4 expression is regulated by changes in peripheral glycaemia and is dysregulated in diabetes, providing a mechanism by which ME oligodendrocytes contribute to the regulation of glucose homeostasis. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1474-9718 25 5 2026 UNC45B Reduction With Aging: A Myofiber-Intrinsic Promoting Factor for Sarcopenia e70502 EN Taiga Mishima Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Taiga Nagamune Department of Life Science and Applied Chemistry, Nagoya Institute of Technology Saori Tada Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Daiki Watanabe Graduate School of Sport and Health Sciences, Osaka University of Health and Sport Sciences Nao Tokuda Graduate School of Health Sciences, Sapporo Medical University Takashi Yamada Graduate School of Health Sciences, Sapporo Medical University Akiko Hashimoto‐Hachiya Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Sayaka Higo‐Yamamoto Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Kohei Kido Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama University Aoi Ikedo Division of Integrative Pathophysiology, Proteo‐Science Center, PIAS, Ehime University Yuuki Imai Division of Integrative Pathophysiology, Proteo‐Science Center, PIAS, Ehime University Ryo Fujita Division of Regenerative Medicine, Transborder Medical Research Center, Institute of Medicine, University of Tsukuba Seiya Mizuno Laboratory Animal Resource Center in Transborder Medical Research Center, Institute of Medicine, University of Tsukuba Satoru Takahashi Laboratory Animal Resource Center in Transborder Medical Research Center, Institute of Medicine, University of Tsukuba Katsutaka Oishi Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Satoru Ato Faculty of Medical Science, Nippon Sport Science University Riki Ogasawara Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Skeletal muscle mass and force decline with age, and the loss of muscle force precedes muscle atrophy. However, the underlying mechanisms remain unclear. Here, we investigated the role of the myosin co-chaperone, uncoordinated mutant number-45 myosin chaperone B (UNC45B), in regulating muscle mass and force. UNC45B expression decreased in mouse gastrocnemius muscle with age, particularly at 24 months old, and adeno-associated virus vector-mediated knockdown of Unc45b in 3-month-old mouse triceps surae muscle first reduced plantar flexor torque and then decreased gastrocnemius muscle mass. In addition, Unc45b knockdown in the triceps surae muscle resulted in lower bone mineral density. While maximum Ca2+-activated force in mechanically skinned fibers was not affected by Unc45b knockdown, Unc45b knockdown decreased the ratio of depolarization-induced force to the maximum Ca2+-activated force. We established tamoxifen-inducible skeletal muscle-specific Unc45b knockout (Unc45b imKO) mice to investigate whether the muscle atrophy and weakness due to the loss of Unc45b impacts metabolism and behavior. We found that Unc45b imKO reduced muscle mass and force at a whole-body level, but did not influence systemic glucose tolerance, insulin sensitivity, or the respiratory exchange ratio. However, Unc45b imKO mice reduced the amount of deeper non-rapid eye movement sleep, locomotor activity, and body temperature during the sleep phase. We conclude that UNC45B is essential for maintaining fast-twitch muscle mass and muscle force. In addition, Unc45b deficiency-mediated muscle loss is also associated with bone fragility, decreased body temperature, and impaired sleep quality. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 31 9 2026 Event-free survival and recurrence patterns after curative resection for locally advanced head and neck squamous cell carcinoma: single-institution real-world outcomes prior to the introduction of perioperative immunotherapy 1890 1900 EN Takuma Makino Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuto Naoi Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Go Hasegawa Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuto Yamasaki Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Noda Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Fujimoto Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junya Matsumoto Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Perioperative immune checkpoint inhibitors have improved outcomes for resectable locally advanced head and neck squamous cell carcinoma (HNSCC). However, real-world surgical outcome data based on contemporary endpoints remain limited.<br> Methods We retrospectively analyzed 233 patients who underwent curative-intent surgery for locally advanced HNSCC. Event-free survival (EFS) and overall survival (OS) were evaluated. Unresectable recurrence-free survival (URFS) was explored as an additional endpoint to capture post-recurrence treatment feasibility. Prognostic factors were assessed using Cox proportional hazards models.<br> Results The median follow-up duration was 18.2 months. The 1-year EFS and OS rates were 67.1% and 89.4%, respectively. pN2 or higher disease, venous invasion, and perineural invasion were identified as independent adverse prognostic factors. Recurrence occurred in 34.8% of patients; among these, disease control at the last follow-up was achieved in 61.7% following curative-intent salvage treatment. Salvage surgery was associated with significantly improved post-recurrence survival (p < 0.001).<br> Conclusions This study provides real-world surgical outcome data for resectable locally advanced HNSCC prior to the introduction of perioperative immunotherapy. Recurrence remains a major clinical challenge, with heterogeneous post-recurrence outcomes influenced by treatment feasibility. These findings may help inform interpretation of treatment outcomes and clinical decision-making in the evolving era of perioperative immunotherapy. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2673-9801 6 3 2026 The Antioxidant Activity of α-Tocopherol Metabolites in Comparison with the Parent Compound in Hepatocytes 26 EN Tomoka Nishio Graduate School of Environmental and Life Science, Okayama University Kasumi Amako Graduate School of Environmental and Life Science, Okayama University Daiki Moriya Graduate School of Environmental and Life Science, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University α-Tocopherol (αT) is the major form of vitamin E. Although it is metabolized in the liver when high levels of αT are present, the function of its metabolites has not yet been fully elucidated. This study aimed to evaluate the antioxidant activities of the αT metabolites, α-carboxyethyl hydroxychroman (αCEHC) and α-carboxymethylbutyl hydroxychroman (αCMBHC), in comparison with their parent compound. The pretreatment with αT and its metabolites showed a cytoprotective effect on the cytotoxicity induced by hydrogen peroxide in the mouse hepatoma Hepa1c1c7 cells. To elucidate the mechanism underlying the effect, in vitro assays and assessments of antioxidant-related genes and proteins were conducted. The in vitro assays showed that these compounds showed little scavenging activity against hydrogen peroxide but exhibited scavenging activity against DPPH radicals. On the other hand, assessments of antioxidant-related genes and proteins showed that αT and its metabolites significantly upregulated the expression of heme oxygenase-1 (HO-1) possibly through activation of the transcript factor Nrf2. Moreover, the cytoprotective effects of αT and its metabolites against hydrogen peroxide were counteracted by HO-1 inhibitors. These results suggest that not only αT but also its metabolites are potential cytoprotective factors against oxidative stress-induced cytotoxicity, and that their effects are exerted not through a direct action of scavenging hydrogen peroxide in the body, but rather through the regulation of gene expression. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 3 2026 Chloride-Transporting OsHKT1;1 Splice Variants and Their Expression Profiles Under Salinity Stress in Rice 1178 EN Shahin Imran Institute of Plant Science and Resources, Okayama University Shuntaro Ono Institute of Plant Science and Resources, Okayama University, Kurashiki 710-0046, Okayama, Japan Rie Horie Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University Maki Katsuhara Institute of Plant Science and Resources, Okayama University Tomoaki Horie Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University OsHKT1;1, a member of the high-affinity K+ transporter (HKT) family, plays a key role in Na+ homeostasis and salinity tolerance in rice. In our previous study, multiple potential OsHKT1;1 splicing variants were identified, as well as the full-length (FL) OsHKT1;1 transcript from the salt-tolerant rice Pokkali. However, most previous studies focused solely on the full-length protein, leaving the transport functions of splice variants largely unexamined. In this study, we focused on the splice variant OsHKT1;1-V2 and compared its function and gene expression with those of OsHKT1;1-FL. Two-electrode voltage clamp experiments using Xenopus laevis oocytes revealed that the 1st start codon of OsHKT1;1-V2 is functional to exhibit bidirectional currents in bath solutions containing NaCl. Unlike the Na+-selective feature of OsHKT1;1-FL, OsHKT1;1-V2 primarily mediated Cl− transport with weak Na+ selectivity, which was supported by the higher Cl− accumulation in OsHKT1;1-V2–expressing oocytes. Subcellular localization analyses using oocytes and Arabidopsis mesophyll cells indicated plasma membrane localization of OsHKT1;1-V2, similar to OsHKT1;1-FL. Functional assays using a yeast mutant further indicated that OsHKT1;1-FL, but not OsHKT1;1-V2, mediates Na+ uptake. The same OsHKT1;1 variants were identified in the japonica cultivar Nipponbare, and OsHKT1;1-V2 of the cultivar showed Cl− transport properties similar to the one from Pokkali. Quantitative PCR analyses revealed higher abundance of OsHKT1;1-FL transcripts in Nipponbare than in Pokkali with markedly lower OsHKT1;1-V2 levels in Pokkali under salt stress. This study provides a new insight into HKT-mediated ion homeostasis under salinity stress. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1873-9601 20 3 2026 Critical role of cellular communication network factor 1 in early osteogenesis of mesenchymal stem cells primed by low‐intensity pulsed ultrasound and bone morphogenetic protein 2 e70101 EN Hsu Myat Paing Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Satoshi Kubota Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Masaharu Takigawa Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Faculty of Medicine Dentistry and Pharmaceutical Sciences Takuo Kuboki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Takashi Nishida Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences There is a known reciprocal inhibitory relationship between adipogenesis and osteogenesis in mesenchymal stem cells (MSCs). Our previous study showed that low-intensity pulsed ultrasound (LIPUS) did not promote osteogenesis of a murine MSC line C3H10T1/2, although LIPUS treatment suppressed adipogenesis. Therefore, we investigated the effect of a combination of an osteoinductive factor such as bone morphogenic protein-2 (BMP-2) and LIPUS treatment on osteogenesis. This combination significantly upregulated the gene expressions of BMP receptors and RUNX2, which is a key early osteogenic transcription factor. Interestingly, cellular communication network factor 1 (CCN1) was significantly increased at the mRNA and protein levels. Additionally, Runx2 expression was increased by a recombinant CCN1 protein and decreased in CRISPR-Cas9-generated Ccn1 knockout (KO) cells treated with the combination of LIPUS treatment and BMP-2. Moreover, Runx2 expression was recovered through the transfection of a Ccn1 expression plasmid into Ccn1 KO cells. These findings indicate that treatment with the combination of LIPUS treatment and BMP-2 promoted CCN1 production, and the CCN1 regulates the Runx2 expression in C3H10T1/2 cells, thus suggesting that CCN1 induced by mechanical stimulation and an osteoinductive factor plays a pivotal role in osteogenesis of MSCs. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1873-9601 20 2 2026 Species‐specific roles of cellular communication network proteins in cartilage development: A comparative study using in vitro chondrogenic models e70089 EN Zhangzheng Wang Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen Judit Vágó Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen Roland Takács Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen Szilárd Póliska Genomic Medicine and Bioinformatics Core Facility Department of Biochemistry and Molecular Biology Faculty of Medicine, University of Debrecen Ee Hyun Kim Department of Biomedical Materials Science Graduate School of JABA, Wonkwang University Eun‐Jung Jin Department of Biomedical Materials Science Graduate School of JABA, Wonkwang University Satoshi Kubota Department of Biochemistry and Molecular Dentistry, Okayama University, Faculty of Medicine, Dentistry and Pharmaceutical Science Celina G Kleer Department of Pathology, University of Michigan Medical School Bernard Perbal International CCN Society Csaba Matta Department of Anatomy, Histology and Embryology Faculty of Medicine, University of Debrecen Cellular communication network (CCN) proteins are key matricellular regulators of cartilage development, yet their species-specific roles and network-level context remain unclear. This study integrated bulk RNA sequencing from chicken and mouse embryonic limb bud micromass cultures and human mesenchymal stem cell chondrogenesis with co-expression, protein–protein interaction, and ortholog analyses to construct CCN-centered regulatory networks across models. CCN1 and CCN2 emerged as dominant, conserved hubs enriched in collagen-containing extracellular matrix, cartilage development, and growth factor signaling modules, whereas CCN3–CCN6 showed lower context-dependent expression and connectivity. Functional and ortholog analyses revealed moderate pathway conservation, with high conservation of IGF, EGFR, and HIF-1 signaling, but reduced overlap in hypoxia and mechanosensing/Hippo categories, indicating species-specific tuning of environmental sensing. A focused ortholog screen identified multifunctional conserved hubs, including COL2A1, TGFBR1, SMAD3, RUNX2, HIF1A, IGF1, SPP1, and CD44. Single-cell RNA-seq meta-analysis of human iPSC-derived chondrogenesis and embryonic limb datasets showed CCN1/2 expression and homologous network activity peaking in mesenchymal and early chondrocyte populations, consistent with model-dependent persistence into hypertrophic and ossification stages in vivo. Overall, this work defines a conserved CCN1/2-centered axis integrating extracellular matrix formation with growth factor and mechanical cues, providing a framework for model selection and CCN-targeted cartilage regeneration strategies. No potential conflict of interest relevant to this article was reported.

The Society for Free Radical Research Japan Acta Medica Okayama 0912-0009 79 2 2026 Organ-specific modulation of antioxidant functions by combined voluntary exercise and radon inhalation in mice 141 149 EN Reiju Takenaka Graduate School of Health Sciences, Okayama University Ayumi Tanaka Graduate School of Health Sciences, Okayama University Shogo Miyanaga Graduate School of Health Sciences, Okayama University Shota Naoe Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Shuna Goto Graduate School of Health Sciences, Okayama University Mitsuki Nagano Graduate School of Health Sciences, Okayama University Kotaro Tano Graduate School of Health Sciences, Okayama University Norie Kanzaki Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Akihiro Sakoda Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Takahiro Kataoka Faculty of Health Sciences, Okayama University Radon inhalation as well as voluntary exercise increase anti­oxidant function in experimental animals. However, the combined effects of radon inhalation and exercise on antioxidant functions have not yet been investigated. In this study, we examined the effects of combined voluntary wheel running (VWR) and radon inhalation on antioxidant functions in various organs of mice. Mice were individually housed in cages equipped with running wheels, and allowed voluntary exercise for 5, 15, or 25 days, followed by radon inhalation at 2,000 Bq/m3 for 24 ‍‍h. Antioxidant function was enhanced by the combined treatment in the kidneys, pancreas, spleen, and stomach, with responses varying according to exercise duration. In contrast, antioxidant function was reduced in the lungs and heart. No clear interaction effects of the combined treatment were observed in the liver, small intestine, colon, and brain. These findings suggest that the combined effects of voluntary exercise and radon inhalation on antioxidant functions are organ-specific and can be categorized into distinct response patterns across tissues. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1939-8425 19 1 2026 GWAS and Candidate Gene Prediction of Elemental Accumulation Traits in Rice Using a Multiparental Population 44 EN Qian Zhang Institute of Plant Science and Resources, Okayama University Tomoyuki Furuta Institute of Plant Science and Resources, Okayama University Kazunari Kashihara Institute of Plant Science and Resources, Okayama University Daisuke Ogawa Institute of Crop Science, National Agriculture and Food Research Organization Junichi Yonemaru Research Center for Agricultural Information Technology, National Agriculture and Food Research Organization Jian Feng Ma Institute of Plant Science and Resources, Okayama University Toshio Yamamoto Institute of Plant Science and Resources, Okayama University Rice plants accumulate essential elements to sustain physiological processes during growth and development and to ensure the nutritional quality of the grain as a food source. However, the genetic basis of elemental accumulation and the interrelationships among elemental concentrations across different tissues remain poorly understood. To conduct breeding aimed at improving the absorption characteristics of multiple interrelated elements, genetic analysis using experimental populations that retain diversity while sharing the genetic background of cultivated varieties is effective. Here we show genetic variations in the concentrations of 13 elements (P, K, Ca, Mg, As, Cd, Cr, Cu, Fe, Mo, Mn, Ni, and Zn) in rice straw at the flowering stage and grain at the mature stage using a multi-parent advanced generation inter-cross (MAGIC) population that derived from eight cultivars including both Japonica and Indica. Comprehensive evaluation of the correlation coefficients revealed divergences in the association between grain and straw for several combinations of elements. Haplotype-based genome-wide association studies (GWAS) identified 51 and 53 quantitative trait loci (QTLs) in straw and grain, respectively. In total, the 104 QTLs were grouped into 19 clusters and 60 independent QTLs. By leveraging the haplotype information from the MAGIC population, 52 candidate genes associated with the accumulation of Ca, Mg, Cd, Cu, Fe, and Mo were efficiently predicted from these QTLs, including both previously reported and novel genes. Among them, OsMOT1;1 encoding a molybdenum transporter, was predicted to be within a QTL associated with Mo accumulation in grain on chromosome 8. OsACA9, a homolog of autoinhibited Ca²⁺-ATPases, was predicted within a QTL related to Ca accumulation in straw on chromosome 2. In addition, an unidentified gene, OsCML6, which is presumed to be involved in calcium signaling, was predicted to be a candidate for a Ca-accumulation QTL on chromosome 11. These findings offer insights into haplotypes and putative genes associated with element accumulation and trait interrelationships, providing valuable information for optimizing plant growth and enhancing grain nutritional quality in rice breeding programs. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0143-4160 137 2026 Activation phosphorylation and dephosphorylation dynamics of Ca2+/Calmodulin-dependent protein kinase Iα in HeLa cells 103183 EN Yerun Chen Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masao Miki 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 Satomi Ohtsuka Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masumi Eto Graduate School of Veterinary Science, Okayama University of Science Atsuhiko Ishida Laboratory of Molecular Brain Science, Graduate School of Integrated Sciences for Life, Hiroshima University Futoshi Suizu Clinical Examination Department, Kagawa Prefectural University of Health Sciences Akihiro Mizutani Department of Pharmacotherapeutics, Showa Pharmaceutical University Hideaki Ando Laboratory for Developmental Neurobiology, RIKEN Center for Brain Science Katsuhiko Mikoshiba Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University Hiroshi Tokumitsu Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ca²⁺/calmodulin-dependent protein kinase I (CaMKI), a multifunctional CaM-activated protein kinase, is involved in various Ca²⁺ signaling pathways including neuronal development. Here, we characterize the phosphorylation at Thr177 (an activation Thr residue) and subsequent dephosphorylation dynamics of CaMKIα in HeLa cells upon physiological stimulation that elevates intracellular Ca²⁺. ATP induced CaMKIα phosphorylation within 5–10 min; phosphorylation was then blocked by CaMKK inhibitor TIM-063, or by the depletion of extracellular Ca²⁺. This was followed by gradual dephosphorylation to basal levels within 30–60 min. Histamine induced CaMKIα phosphorylation, peaking within 3–4 min; this process was abolished by treatment with either TIM-063 or intracellular Ca²⁺ chelation using BAPTA-AM and thapsigargin; however, not by extracellular Ca²⁺ depletion. CaMKIα was then rapidly dephosphorylated to basal levels within 10 min. Consistently, histamine-induced (but not ATP-induced) CaMKIα phosphorylation was absent in triple IP₃ receptor-knockout HeLa cells. Dephosphorylation of CaMKIα after ATP-induced phosphorylation was unaffected by okadaic acid or CaMK phosphatase (CaMKP, known as PPM1F) inhibitors (ANS and ANDS). We found that HeLa cell extracts contained Mg2+/Mn2+-dependent CaMKIα dephosphorylation activity that was insensitive to ANS and ANDS. Furthermore, co-expression of PP2Cα fully abolished ATP-, histamine-, or ionomycin-stimulated CaMKIα phosphorylation, which is consistent with in vitro dephosphorylation of CaMKIα at Thr177 by recombinant PP2Cα. Taken together, these results reveal that agonist-induced Ca²⁺ influx from the extracellular space or release from intracellular stores transiently activates CaMKK-CaMKIα signaling in HeLa cells, which is shut off by dephosphorylation catalyzed by PP2Cα as a promising candidate for CaMKIα phosphatase. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 2165-0497 14 9 2026 Combinations of long terminal repeat and tax protein substitutions influence bovine leukemia virus transmission through altered viral productivity e0086926 EN Hironobu Murakami School of Veterinary Medicine, Azabu University Reiichiro Sato Graduate School of Medicine and Veterinary Medicine, University of Miyazaki Jumpei Uchiyama Department of Infectious Diseases, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Kazuyuki Sogawa School of Life and EnvironmentaScience, Azabu University Hiroho Ishida School of Veterinary Medicine, Azabu University Makoto Nagai School of Veterinary Medicine, Azabu University Bovine leukemia virus (BLV) infection imposes a substantial economic burden on the global cattle industry. Although proviral load (PVL) in blood influences transmission, the effects of viral genetic variations, including the high viral production-associated long terminal repeat (LTR) substitution at nucleotide position 175 (LTR175), on herd-level dynamics remain unclear. This study investigated the effects of specific substitutions on the regulation of viral productivity and transmission. Longitudinal monitoring of a single farm (herd size: 50–68 cows; 438 samples collected) over a 7-year period revealed that viral strains carrying cytosine at LTR175 (LTR175C) significantly increased in frequency, becoming dominant over wild-type strains carrying thymidine. In contrast, amino acid substitutions in the Tax protein at positions 69 (Tax69) and 73 (Tax73) modified viral transactivation independent of LTR175. Structural modeling via AlphaFold2 predicted that Tax69 and Tax73 mutations alter protein properties, suggesting modulation of transactivation activity. Consistent with this prediction, in vitro assays confirmed that the substitutions modified viral production by regulating transactivation independent of LTR175. Moreover, high viral-productivity haplotypes containing LTR175C and Tax73Q (glutamine at amino acid residue 73) exhibited a transmission advantage within the herd, even when host PVL levels were not significantly elevated. These findings suggest that cellular-level viral productivity is one of the key determinants of transmission fitness. Overall, this study revealed a regulatory interaction between the LTR and Tax protein that optimizes viral spread and highlights the need for control strategies that account for viral genetic substitutions. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0918-9440 139 2 2026 Knockout of a single aquaporin, OsPIP2;4, decreases root water permeability in rice 255 265 EN Aya Onishi Institute of Plant Science and Resources, Okayama University Tomoaki Horie Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University Ryo Ishitsuka Institute of Plant Science and Resources, Okayama University Shizuka Sasano Institute of Plant Science and Resources, Okayama University Rie Horie Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University Yunosuke Mito Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University Shigeko Utsugi Institute of Plant Science and Resources, Okayama University Junko Ishikawa Institute of Crop Science, NARO Majid Mahdieh Institute of Plant Science and Resources, Okayama University Maki Katsuhara Institute of Plant Science and Resources, Okayama University Aquaporins (AQPs) are membrane proteins that facilitate water transport and are present in nearly all bacterial, animal, and plant cells. In plants, AQPs are classified into four or more subfamilies, with plasma membrane intrinsic proteins (PIPs) playing a key role in root water uptake and cellular water regulation. Previous studies have demonstrated that PIPs contribute to root hydraulic conductivity (Lpr) in various plant species. In this study, we examined the specific role of OsPIP2;4, one of the PIP-type aquaporins among 11 rice (Oryza sativa) PIP2s, in regulating Lpr. Transgenic rice plants, including OsPIP2;4-knockout (KO) and overexpressing (Ox) lines, were used for this investigation. Two independent KO lines, generated via the CRISPR-Cas9 system and T-DNA insertion mutagenesis, respectively, showed significantly lower Lpr compared to wild-type rice plants. The decrease in Lpr in the T-DNA KO line was associated with reduced OsPIP2;4 transcript levels, measured by real-time PCR, and lower OsPIP2;4 protein levels, as shown by immunohistochemical analysis. Conversely, no notable increase in Lpr was observed in the Ox lines. These results suggest that OsPIP2;4 is expressed in appropriate tissues in rice roots and is a key factor influencing Lpr. This research represents a significant step toward further understanding the physiological functions of OsPIP2;4 in rice. No potential conflict of interest relevant to this article was reported.

岡山大学法学会 Acta Medica Okayama 0386-3050 76 1 2026 裏表紙・英文目次 EN No potential conflict of interest relevant to this article was reported.

岡山大学法学会 Acta Medica Okayama 0386-3050 76 1 2026 奥付 EN No potential conflict of interest relevant to this article was reported.

岡山大学法学会 Acta Medica Okayama 0386-3050 76 1 2026 本号執筆者紹介 293 293 EN No potential conflict of interest relevant to this article was reported.

岡山大学法学会 Acta Medica Okayama 0386-3050 76 1 2026 アスベスト被害をめぐる因果関係の主張立証の壁⑴ ―建設アスベスト給付金制度（１人親方等）の問題を中心に― 52 35 EN H. Tsuji No potential conflict of interest relevant to this article was reported.

岡山大学法学会 Acta Medica Okayama 0386-3050 76 1 2026 昭和８年児童虐待防止法の実施状況 292 54 EN Y. Oizumi No potential conflict of interest relevant to this article was reported.

岡山大学法学会 Acta Medica Okayama 0386-3050 76 1 2026 ヤン＝ヴェルナー・ミュラーの冷戦リベラリズム論 ―節度ある感受性から戦闘的信念へ― 1 33 EN D. Odagawa No potential conflict of interest relevant to this article was reported.

岡山大学法学会 Acta Medica Okayama 0386-3050 76 1 2026 表紙・目次 EN No potential conflict of interest relevant to this article was reported.

一般社団法人 電気学会 Acta Medica Okayama 0385-4221 146 9 2026 多様な電力消費形態を考慮したスマートグリッド運用の最適化 864 876 EN Takaki Kawamoto Faculty of Environmental, Life, Natural Science and Technology, Okayama University Yuriko Toda School of Creative Science and Engineering, Waseda University Takashi Hasuike School of Creative Science and Engineering, Waseda University 　This study examines an optimal operation model for a smart grid composed of multiple microgrids to promote renewable energy use in Japan. In Japan, about 70% of electricity is still supplied by fossil fuel power, while renewables account for only 18% despite a 36–38% target for 2030. Using demand and photovoltaic data from Setagaya Ward, we construct a system model with factory/office and residential microgrids and formulate a mathematical optimization model that considers power interchange, batteries and heat storage. Numerical experiments based on several case studies show the effectiveness of smart grid operation designed according to the proposed model in promoting renewable energy utilization and reducing total generation cost. In particular, the results show that increasing photovoltaic capacity, increasing the number of microgrids, and considering heat demand are all effective measures. However, these benefits depend on the season. Future work should extend the system model to account for seasonal variability and associated investment costs. 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 192 2026 裏表紙・英文目次 EN No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 192 2026 奥付 EN 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 192 2026 マット運動の側方倒立回転に関する認識の実態 ― 素朴概念に基づく調査と考察 ― 161 169 EN Toru TAKAHASHI Faculty of Education, Okayama University Kousuke SAKAMOTO International Pacific University Ken HIRONO UCHIDA YOKO CO., LTD. 10.18926/bgeou/71152 　本研究の目的は，小学校体育科，および中学校・高等学校保健体育科の器械運動領域で取り扱われる「側方倒立回転」に関する認識の実態を素朴概念に基づく調査を通して明らかにすることであった。素朴概念とは学習者が日常生活において経験的に獲得した知識，もしくは学校の授業等で学習する科学的概念とは必ずしも一致しない知識を指し示す用語である。本研究にて側方倒立回転という技を取り上げた理由とは，運動の形態上4パターンの実施方法が存在しているにも関わらず，合理的，かつ行い易い実施方法はそのうちの2パターンに限定されるという特殊性にある。本研究では側方倒立回転に対する素朴概念を明らかにするために，その認識を問うためのアンケート調査を実施した。調査期間は2023年6月7月，調査対象はA大学小学校教員養成課程に在籍する学生140名であった。調査の結果140名中35名，割合にすると32.1％が誤った知識を素朴概念として保有していたということが明らかとなった。 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 192 2026 ダンスを通じた共生社会の実現に向けた地域協働プロジェクト ― 岡山うらじゃ祭りにおけるインクルーシブダンス実践 ― 147 159 EN Risako YOSHIMURA The Joint Graduate School in Science of School Education, Hyogo University of Teacher Education Aito ODA Resorttrust, Inc. Wing In CHIU The Joint Graduate School in Science of School Education, Hyogo University of Teacher Education Sayaka TANIGAWA The Joint Graduate School in Science of School Education, Hyogo University of Teacher Education Haruko SAKO Faculty of Education, Okayama University 10.18926/bgeou/71151 　障がい者の文化芸術活動では，障がい者が創造や発信に主体的に関わることが重視されている。しかし，その一形態であるインクルーシブダンスを地域社会に開かれた文化活動へと展開する事例の分析は十分ではない。そこで本稿では，岡山県の「うらじゃ」祭りにおいて発足したインクルーシブ踊り連「一期一会〜輪舞温羅」を対象に，インクルーシブうらじゃダンスの開発および実践過程を整理した。活動記録，映像記録，活動資料をもとに分析した結果，表現内容や実施方法，演舞環境が，参加者の心身の特性を踏まえて段階的に調整されていたことが明らかとなった。また，参加者の主観的運動強度は主に「楽」から「ややきつい」の範囲に分布し，活動満足度も高い傾向を示した。以上より，本プロジェクトは，地域文化を基盤としたインクルーシブな身体表現活動に関する基礎的知見を提供するものであると考えられる。 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 192 2026 岡山大学教育学部初等家庭科必修科目を通した学生の教科観の深化 ―2024-2025年度のアンケート調査の結果から― 137 146 EN Chiharu MORI Faculty of Education, Okayama University Miyuki HISANARI Faculty of Education, Okayama University Yoko SHINOHARA Faculty of Education, Okayama University Kyoungwon LEE Faculty of Education, Okayama University 10.18926/bgeou/71150 　本研究では，岡山大学教育学部新カリキュラムにおける，初等家庭科の必修科目「内容構成基礎」，「指導法基礎」，「指導法�T」の3科目を通して，履修学生の家庭科に対する教科観（イメージや考え方）がどのように変化したのかを，アンケート調査を用いて明らかにすることを目的とした。「指導する立場から小学校家庭科を学修して，家庭科のイメージや考え方が変化した」に対する5件法の回答では，「あてはまる」，「ややあてはまる」を合わせた肯定的な回答の割合は，「内容構成基礎」90.1%，「指導法基礎」88.5%，「指導法�T」95.0%と，「指導法基礎」でやや下がったものの，「指導法�T」で最も高い割合を示した。自由記述のテキスト分析では，必修科目の学修を通した学生の教科観は，「教科の学習内容の理解」→「教科理念の理解」→「教科指導の理解」の段階を踏むことにより，徐々に深化したと推察された。 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 192 2026 「創造性が社会と出会う美術教育」による教員の学びに関する基礎研究�V ― 中学校美術科教員の授業記録と追跡インタビューに基づく事例研究― 125 135 EN Ai MATSUURA Faculty of Education, Okayama University Yusuke SENOO Okayama Prefectural Tamashima High School Hitoshi KIMURA Shiga University Faculty of Education Elementary School Soichiro TAKEDA Okayama University Junior High School Chande SON Osaka Kyoiku University Tennoji Junior High School Tetsuo KIYOTA Faculty of Education, Okayama University 10.18926/bgeou/71149 　本論は，学校外の他者との対話経験が，中学校美術科教員の授業実践においてどのように意味づけられていたのかを明らかにすることを目的とする。市井プロジェクトに参加した教諭Bを対象に，市井インタビュー後に実施された表現活動の授業記録と，授業実践後の追跡インタビューを照合した。その結果，教諭Bは，学校外の他者との対話経験を，授業方法の直接的な変更としてではなく，授業中の判断，生徒理解，題材・表現理解，生活実践との関係において意味づけていたことが確認された。特に，生徒の行動や表現を統制する見方から，その背景や生成過程を見取る見方への移行があった可能性が高い。以上のことから，本論により教師の学びを学校内の研修や同僚性に限定せず学校外の生活世界との関係から捉える意義が示唆された。 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 192 2026 中国地方広域中心都市における人口移動の動向 ―岡山県岡山市の事例― 109 124 EN Masao NOBE Faculty of Education, Okayama University 10.18926/bgeou/71148 　本稿の目的は，2006年から2025年までの岡山市における人口移動を分析し，その動向を明らかにすることである。21世紀に入って以降，岡山市では中心市街地の再開発や分譲マンション供給の拡大により，都心回帰が進展してきた。また，リーマンショックや東日本大震災，新型コロナウイルス感染症の拡大といった出来事も，人口移動に一定の影響を及ぼしたと考えられる。しかし，こうした外部要因にもかかわらず，人口移動の基本的な趨勢に大きな変化はみられなかった。すなわち，岡山市は県内の大部分の圏域および県外の周辺地域から人口を吸収する一方で，三大都市圏を含む関東・近畿・中部地方へ人口を送り出している。 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 192 2026 ウィーン体制における勢力圏 ―1820年代の露墺関係を中心に― 91 107 EN Hiroaki YAGUCHI Faculty of Education, Okayama University 10.18926/bgeou/71147 　国際政治上，頻繁に言及される現象にもかかわらず，「勢力圏」とその概念は十分に整理されていない。本稿では，1820年代ロシアのイタリア半島におけるオーストリアの勢力範囲に対する認識を事例に，19世紀前半のヨーロッパ国際社会における勢力圏のあり方を検討した。とりわけロシアは，1820年代を通じてバルカン半島で継続したギリシア独立革命への干渉を認めさせるべく，1820年代初頭のナポリ立憲革命を鎮圧したオーストリアの干渉の先例に繰り返し言及していた。その結果としてロシアの政策決定者たちは，1820年代初頭には完全に受け入れていなかった，イタリア半島におけるオーストリアの特別な利益の存在を認めるに至った。そして1830年のフランス七月革命の結果として，露墺両国は，バルカン半島とイタリア半島における双方の利益と勢力範囲をお互いに受け入れた。19世紀前半のウィーン体制期の勢力圏は，長期的な交渉の繰り返しで形成・構築されるものであり，認識のすり合わせが成功した場合には，大国間の外交的協力を可能にした。 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 192 2026 法に基づく初等社会科内容構成に関する研究 ―米国法教育教材『民主主義の基礎(FOUNDATIONS of DEMOCRACY)』を手掛かりにして― 79 90 EN Toshinori KUWABARA Faculty of Education, Okayama University Shinnosuke FUKUNAGA Okayama University Graduate School of Education Master's Course 10.18926/bgeou/71146 　本研究は，法に基づいて構成される初等教育段階の社会科の内容構成原理を明らかにするため，米国の初等法教育教材『民主主義の基礎（FOUNDATIONS of DEMOCRACY）』を分析したものである。日本における法教育研究は，1990年代後半から，米国の法教育研究を紹介する形で始まり，その後，数多くの米国の法関連教育教材が日本に紹介され，その分析に基づく研究成果が蓄積されてきた。しかし，それらの研究の多くは，中等教育段階のものであり，初等教育を対象とする法教育の研究は多くはない。本研究は，初等社会科としての法教育に焦点を当て，その内容構成を明らかにしようとする点に独自性がある。本研究で取り上げる『民主主義の基礎』は，日本でも注目され，複数の研究者によって分析されている。本研究では，それらの先行研究をふまえつつ，これまでの研究では十分解明されていなかった内容構成原理の解明を目指す。 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 192 2026 子どもの自己が立ち上がる造形行為についての文献研究 ― 木村敏の文献に基づいた子どもの学びを捉える視点 ― 69 77 EN Shuya OHIRA Faculty of Education, Okayama University 10.18926/bgeou/71145 　本研究では，造形行為において，子どもの「自己」が立ち上がることをその子ども自身の学びとして捉える視点について，木村の文献を手掛かりに検討した。まず，「自我」，「無意識」，「自己」の概念を整理し，造形行為において個々の子どもに経験される学びを考察した。次に，個々の子どもに経験される学びが，活動場所や造形行為を共有する他の子どもへと知られ受容されていく関係が，造形行為の過程で形成されることを考察した。最後に，造形行為において形成される子ども同士の関係へと参与し，同じ経験を共有していくあり方が，子どもの「自己」が立ち上がる学びを捉える視点そのものであることを示した。今後は，芸術教育や芸術実践を対象とした研究により，本研究の知見を深めていく。 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 192 2026 ０歳児クラスにおける負の情動調整を支える保育実践の構造 ―保育者へのグループインタビューの SCAT 分析― 53 67 EN Mika KATAYAMA Faculty of Education, Okayama University Sachiyo OKAMURA Tachibanaima Nursery School of the Tachibana Social Welfare Association 10.18926/bgeou/71144 　本研究の目的は，０歳児クラスにおける乳児の負の情動調整を支える保育実践の構造を明らかにすることである。０歳児クラス担当保育者２名を対象にフォーカス・グループ・インタビューを実施し，逐語録をSCAT により分析した。その結果，【受容的共同調整による情緒的安全基地の形成】【子どもの心情の理解に基づく見立ての深化】【子どもの心情の予測に基づく情動調整】【保育者間協働による情動調整の実践の共有】【好みや文化的媒介を活用した情動安定化】の５つの統合カテゴリーが導出された。保育者が子どもの心情変化を見取りながら，待機・見守り・最小限の介入を調整する「子どもの心情の予測に基づく情動調整」が特徴的であった。情動調整支援が保育者間の協働的実践で支えられていることも明らかになった。 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 192 2026 聴覚障害学生支援のための初学者向け大学ノートテイカー共同養成研修の効果・課題・あり方 ―多様な人的リソースを活用した養成研修モデルの検討― 37 51 EN Takeshi SHIMONAKAMURA Faculty of Education, Okayama University Hiroko INOUE Child Consultation Center, Kumamoto city Yuka TAKAGI Student Accessibility Support Room, Kumamoto University Hirofumi SOEJIMA Student Accessibility Support Room, Kumamoto University Noboru FUJISE Kumamoto Prefecture Mental Health Welfare Center 10.18926/bgeou/71143 　本研究は，多様な人的リソースを活用した聴覚障害学生支援のための初学者向けノートテイカー共同養成研修の効果と課題を明らかにし，今後の共同養成研修のあり方について検討することを目的とした。共同養成研修の効果として，【他大学との交流の有効性】，【研修順序の有効性】，【研修内容の充実】などが見られ，今後の研修の生かし方として，【研鑽や活動拡大】，【支援・研修の充実】などが挙げられており，研修の有効性が明らかになった。一方で，共同養成研修の課題として，交流プログラムの満足度が相対的に最も低く，【時間不足】が背景にあると考えられた。これらのことを踏まえて，共同養成研修のあり方として，学生・教職員が交流する十分な時間の確保や，各講義時間の増加のために，動画を視聴するオンデマンド形式を基本として，交流や演習などを対面，またはリアルタイムオンラインで実施するなどの研修方法が考えられる。 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 192 2026 大学生の主観的幸福感，幸福への動機づけを規定する心理的要因 ―本来感，対人関係，エンゲージメントに着目して― 27 36 EN Tazuko AOKI Faculty of Education, Okayama University Miki HARADA Elementary School teacher in Okayama Prefecture 10.18926/bgeou/71142 　本研究は，大学生の幸福感を規定する心理的要因を明らかにすることを目的とし，主観的幸福感（SHS）および幸せへの動機づけ（HEMA）を従属変数として，本来感，対人関係（被受容感・被拒絶感），エンゲージメント（感情・認識）との関連を検討した。大学生139名を対象に質問紙調査を実施し，相関分析および重回帰分析を行った。その結果，主観的幸福感には本来感と感情エンゲージメントが正の影響を，被拒絶感が負の影響を与えていた。幸せへの動機づけのうち，幸福追求と喜び追求には本来感が正の影響を示し，幸福追求には感情エンゲージメントと認識エンゲージメントも関連していた。一方，くつろぎ追求にはいずれの要因も有意な影響を示さなかった。以上より，大学生の幸福感は，自分らしく行動できている感覚や活動への積極的関与によって高まり，他者からの拒絶感は幸福感を低下させることが示唆された。 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 192 2026 集団活動での協働経験を通じて培われるリーダーシップ効力感 ― 経験を振り返る習慣がもつ意味 ― 13 26 EN Ryo MISAWA Faculty of Education, Okayama University Shunta KANEMI Benesse Corporation Naoko HASEGAWA Faculty of Human Sciences, Department of Psychology, Bunkyo University 10.18926/bgeou/71141 　本研究では，日常的な集団活動での協働経験および経験学習習慣が，リーダーシップ効力感とどのように関連するのかを検討した。大学生を対象に質問紙調査を実施し，99名の有効回答を分析対象とした。因子分析により，協働経験について「協働的問題解決」，「集団内責任遂行」，「意思決定参画」の3因子が抽出された。リーダーシップ効力感（鼓舞力，変革力，共感力）との関連を階層的重回帰分析で検討した結果，集団内責任遂行の経験は変革力と，意思決定参画の経験は鼓舞力と関連し，経験学習習慣は変革力および共感力と正の関連を示した。また，協働的問題解決の経験が少ない場合には，経験学習習慣が鼓舞力と変革力を補完的に高める可能性が示唆された。得られた知見に基づき，大学生のリーダーシップ育成における協働経験の内容に応じた支援と，経験を省察する習慣形成の重要性を議論した。 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 192 2026 19世紀後半日本における一斉教授法の受容の一断面 ― 近世・近代転換期の教育状況の視野 ― 1 12 EN Kazuaki KAJII Faculty of Education, Okayama University 10.18926/bgeou/71140 　近代日本における西洋教育の日本教育への影響を考察し，とくに世界で伝播のあったモニトリアル・システム（助教法）の日本教育における位置を検討する。19世紀後半は，近世の寺子屋の時代から近代の小学校の時代への転換期であった。国民教育の場としての小学校が整い，男女が就学する状況の形成があった。この過程において，日本がアメリカ経由で受容した一斉教授は，教師が教室で教授する方法であった。助教を用いる方法ではなかった。本稿は，近代日本ではモニトリアル･システムを基本的には経験しない展開と，一斉教授を行う教師の養成があったことを論じるものである。 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 192 2026 表紙・目次 EN No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2666-5174 11 2026 Interbacterial antagonism mediates plant growth modulation by rhizosphere synthetic communities in barley 100639 EN Md Asif Mahamud Institute of Plant Science and Resources, Okayama University Rungnapa Pichaikarn School of Science, Walailak University Muhammad Ammar Latif Institute of Plant Science and Resources, Okayama University Takakazu Matsuura Institute of Plant Science and Resources, Okayama University Izumi C Mori Institute of Plant Science and Resources, Okayama University Daisuke Saisho Institute of Plant Science and Resources, Okayama University Pakpimol Ungcharoenwiwat School of Science, Walailak University Akio Tani Institute of Plant Science and Resources, Okayama University Microbial communities in plant roots are shaped by complex interbacterial interactions, yet how these interactions translate into plant fitness remains poorly understood. In this study, 127 bacterial isolates were obtained from barley (Hordeum vulgare L.) roots of two cultivars grown in a non-fertilized field, representing 45 genera and 72 species. Screening identified isolates with growth-promoting, growth-reducing, and neutral phenotypes. Co-inoculation experiments using synthetic communities (SynComs) demonstrated that growth-promoting isolates effectively cancelled the inhibitory effects of growth-reducing isolates on barley seedling growth. Mechanistic investigation revealed that growth-promoting isolates Variovorax sp. 14F-2.1 and Pseudomonas sp. 37A kill growth-reducing isolates Flavobacterium sp. 2D-1 through direct cell-to-cell contact. Deletion of the Type VI secretion system (T6SS) gene tssA in Variovorax sp. 14F-2.1 substantially reduced this activity, implicating T6SS as a key antagonistic mechanism. Phytohormone profiling revealed that growth-promoting and neutral isolates, but not growth-reducing isolates, produce cytokinins, and only Variovorax sp. 14F-2.1 could degrade IAA, suggesting a potential hormonal basis for differential growth effects. A two-year field microbiome study showed that fertilization regimen and seasonal sampling times were dominant drivers of rhizosphere community composition, while bacterial inoculation had limited and inconsistent effects on microbial diversity and plant growth under field conditions. These results demonstrate that interbacterial antagonism is a key determinant of community-level plant growth outcomes and highlight the complexity of translating laboratory inoculant effects to field settings. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1523-7060 28 1 2025 Optimization of the External Directing Group Depending on the Substrates for the Regioselective C–H Alkenylation of Phenyl Ethers 94 99 EN Koki Yano Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Sawada Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Using an external directing group (externalDG), we have succeeded in ortho-selective C–H alkenylation of various DG-free phenyl ethers, including bulky silyl ethers. Also, we demonstrated a strategy to develop regioselective C–H activation by optimizing externalDG depending on the substrate. The means for optimizing externalDG include the selection of the precursor, the addition of a Lewis acid, and changing the ratio of the precursor/Pd, to control the reactivity and regioselectivity. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 17 2026 Assessment of the Association of Periodontitis and Diabetes Mellitus with Alzheimer’s Disease in a Mouse Model 7542 EN Momoko Nakahara Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Kataoka 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 Mohammad Nurhamim Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Yixuan Zhang Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Daiki Fukuhara Department of Preventive Dentistry, Dental School, Okayama University Yoko Uchida-Fukuhara Laboratory of Biological Anthropology, Research Center for Integrative Evolutionary Science, The Graduate University for Advanced Studies, SOKENDAI Md Monirul Islam Centre for Policy Studies, University College Cork Manabu Morita Department of Oral Health Sciences, Faculty of Health Care Sciences, Takarazuka University of Medical and Health Care Takashi Saito Department of Neuropathology, Graduate School of Medicine, The University of Tokyo Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The purpose of the present study was to investigate how periodontitis and diabetes mellitus (DM) are associated with Alzheimer’s disease (AD) through microRNA (miRNA) using AD model mice. The experimental period was 8 weeks. Twenty-four male knock-in mice (B6-AppNL-G-F/NL-G-F/J) were divided into four groups: control group fed a normal diet (C), DM group fed a high-fat/sucrose diet (DM), periodontitis (P) group, and DM + periodontitis (DM+P) group. Memory performance was compared using the Y-maze test. Next-generation sequencing was performed on brain samples, and fold changes in miRNA expression were calculated by comparing the DM+P and C groups. Integrated miRNA–mRNA analysis identified putative miRNA-targeted mRNAs, and protein expression of the top candidate gene was assessed. Memory function in the DM+P group was significantly lower than in the C group. Among the seven mRNAs identified by the integrated analysis, Neurod1 showed the greatest decrease in expression, and it was predicted to be regulated by miR-693-3p. Neurod1 protein expression in the hippocampus was significantly lower in the DM+P group than the C group. Our results suggest that the combined exposure to periodontitis and DM was associated with AD-like pathological changes and identified the miR-693-3p/Neurod1 pair as a candidate regulatory axis. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0005-2728 1867 4 2026 Cryo-EM structure of photosystem II D1-V185T mutant from Thermosynechococcus vestitus 149598 EN Haowei Jiang Research Institute for Interdisciplinary Science, Advanced Research Field and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiki Nakajima Research Institute for Interdisciplinary Science, Advanced Research Field and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Fusamichi Akita Research Institute for Interdisciplinary Science, Advanced Research Field and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hongjie Li Center for Transformative Science, School of Life Science and Technology and Shanghai Clinical Research and Trial Center, ShanghaiTech University Koji Kato Research Institute for Interdisciplinary Science, Advanced Research Field and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Miwa Sugiura Proteo-Science Research Center, Ehime University Jian-Ren Shen Research Institute for Interdisciplinary Science, Advanced Research Field and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Photosystem II (PSII) catalyzes water oxidation into electrons, protons and dioxygen at its catalytic center, a Mn4CaO5 cluster, utilizing light energy. An amino acid residue D1-V185 in the D1 protein is located close to the Mn4CaO5 cluster, and plays a critical role in its catalytic function. In this research we purified PSII dimers from a D1-V185T mutant of Thermosynechococcus vestitus and analyzed its structure using low-damage cryo-electron microscopy (cryo-EM) at a resolution of 1.88 Å. The results revealed the presence of multi-conformations at the mutation site. Unlike the wild-type valine, which does not allow water molecules to be able to form hydrogen-bonds with it, both conformations of the mutant formed hydrogen bonds with nearby water molecules, which leads to rearrangement of the hydrogen bond networks in the O1 and Cl-1 channels. In conformation-A, the mutated Thr residue forms a hydrogen bond with a water molecule W6, which creates a new channel that bypasses the original O1 channel. Due to the hydrophilic OH group of Thr, the side-chain of D1-Glu189 was attracted and shifted toward the mutant Thr residue. In conformation-B, it forms a hydrogen bond with a water molecule W9 in the Cl-1 channel, bringing W9 closer and thereby disrupting the hydrogen bond network of the Cl-1 channel. In addition, multi-conformations of D2-K317, which is a ligand of Cl-1, were found in the mutant. These changes alter the environment surrounding the Cl-1 ion and Mn4CaO5, thereby affecting the PSII water-oxidation activity. 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 Microstructural changes in irradiated teeth revealed by swept-source optical coherence tomography 22258 EN Kumiko Matsuzaki Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital Hidenobu Matsuzaki Department of Oral Diagnosis and Dentomaxillofacial Radiology, Okayama University Hospital Tomoko Tabata Department of Cariology and Operative Dentistry, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Hideki Aoyama Central Division of Radiology, Okayama University Hospital Kotaro Yoshio Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirotaka Kosaki Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital Naoko Ohara Department of Operative Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Alireza Sadr Biomimetics Biomaterials Biophotonics Biomechanics & Technology Laboratory, Department of Restorative Dentistry, Magnuson Health Sciences Center, University of Washington Yoshihiko Soga Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital Yasushi Shimada Department of Cariology and Operative Dentistry, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Radiation-induced caries is a late complication of radiotherapy for head and neck cancers. Although direct irradiation-induced changes in tooth structure may contribute to its development, these changes have not been fully characterized. This study evaluated irradiation-associated microstructural alterations and tissue density changes in human teeth using swept-source optical coherence tomography (SS-OCT). Eight extracted fully impacted human third molars were assigned to irradiated and non-irradiated groups (n = 4 each). The irradiated group received X-rays at a total dose of 70 Gy, a clinically relevant dose in definitive radiotherapy for head and neck cancer. A total of 64 SS-OCT cross-sectional images were obtained and analyzed, with 32 images from each group, including 16 from the coronal area on the occlusal side and 16 from the cervical area. Microcrack-like features were observed in 100% (16/16) of irradiated and 31.3% (5/16) of non-irradiated images in the coronal area on the occlusal side, and in 43.8% (7/16) and 0% (0/16) of images in the cervical area, respectively. Attenuation coefficients were significantly higher in irradiated enamel and dentin. These findings suggest that irradiation-induced microstructural changes in extracted human teeth in vitro may contribute to increased susceptibility to radiation-induced caries. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 138 2 2026 第125回　岡山医学会総会 80 86 EN No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 138 2 2026 第33回日本ステロイドホルモン学会学術集会 78 79 EN Fumio Otsuka Department of General Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 138 2 2026 第５回日本周産期麻酔科学会学術集会開催報告 76 77 EN Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 138 2 2026 病理診断の国際的標準化 71 73 EN Hidetaka Yamamoto Department of Pathology and Oncology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 138 2 2026 薬物相互作用（66―オレキシン受容体拮抗薬の薬物相互作用） 68 70 EN Yuka Narumoto Department of Pharmacy, Okayama University Hospital Hirofumi Hamano Department of Pharmacy, Medical Development Field, Okayama University Yoshito Zamami Department of Pharmacy, Medical Development Field, Okayama University No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 138 2 2026 肺癌における分子標的治療の新展開―抗体医薬時代の到来― 62 67 EN Tomoka Nishimura Department of Respiratory Medicine, Okayama University Hospital Go Makimoto Department of Respiratory Medicine, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 138 2 2026 自然脱落した子宮原発 DLBCL に対して Pola-R-CHP 療法と CNS 再発予防を行った１例 58 61 EN Hikaru Osada Department of Hematology, Japanese Red Cross Okayama Hospital Maiko Kimura Department of Hematology, Japanese Red Cross Okayama Hospital Manaka Muneishi Department of Hematology, Japanese Red Cross Okayama Hospital Kozo Murayama Department of Hematology, Japanese Red Cross Okayama Hospital Daigo Niiya Department of Hematology, Japanese Red Cross Okayama Hospital Makoto Takeuchi Department of Hematology, Japanese Red Cross Okayama Hospital Soichiro Fujii Department of Hematology, Japanese Red Cross Okayama Hospital 　A 55-year-old woman presented to her local physician with the chief complaint of genital bleeding. A 22×19-mm mass was noted on the patient's cervix, and during the internal examination the mass auto-amputated. The pathological examination of the auto-amputated mass revealed diffuse large B-cell lymphoma (DLBCL). An examination by F-fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) showed FDG uptake at physiological levels in the cervix, with no abnormal uptake in other organs. Cervical tissue was sampled after the spontaneous detachment of the cervical mass, and the biopsy of the cervical mass did not reveal findings suggestive of lymphoma. Six courses of chemotherapy with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisolone (Pola-R-CHP) plus an intramedually injection of methotrexate, cytarabine, and predonisolone (IT-triple), followed by two courses of high-dose intrathecal methotrexate (HD-MTX) were adiministered, and the patient has remained recurrence-free for the more than 8 months since the completion of this treatment. Primary uterine DLBCL is an extremely rare disease with a high rate of recurrence in the central nervous system and a poor prognosis. Our search of the relevant literature identified very few reports describing the prognoses of cases with spontaneous tumor detachment. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 138 2 2026 細菌性コラゲナーゼの構造活性相関と医療応用 50 57 EN Osamu Matsushita Professor Emeritus, Okayama University No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 138 2 2026 感染症学分野創設マニフェスト―日本屈指の感染症研究拠点を目指して― 45 49 EN Hideharu Hagiya Department of Infectious Diseases, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 138 2 2026 ３型免疫応答による腸管恒常性維持および自己免疫性関節炎誘導機構 40 44 EN Keiji Hirota Department of Immunology and Inflammation, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 138 2 2026 令和７年度岡山医学会賞　がん研究奨励賞（林原賞・山田賞） 38 39 EN Hibiki Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 138 2 2026 令和７年度岡山医学会賞　胸部・循環研究奨励賞（砂田賞） 35 37 EN Yoshihiko Itoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 138 2 2026 令和７年度岡山医学会賞　総合研究奨励賞（結城賞） 31 34 EN Yui Kambara Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1662-5110 20 2026 New mechanistic insight into SARM1 activation: TRIM32-mediated ubiquitination is a key lever that actuates SARM1’s catalytic action, leading to axon degeneration and cell death 1842408 EN Hitoshi Murata Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nahoko Tomonobu Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-ichi Yamamoto Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Kinoshita Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sterile alpha and TIR motif-containing protein 1 (SARM1) is an enzyme that cleaves nicotinamide adenine dinucleotide (NAD+) and plays a role in disrupting neural circuits through axon degeneration and cell death. SARM1 is activated by changes in the nicotinamide mononucleotide (NMN)/NAD+ ratio and by various post-translational modifications, but its complete regulatory mechanism remains poorly understood. Here, we report that tripartite motif-containing protein 32 (TRIM32) activates SARM1 through specific ubiquitination triggered by anticancer drug treatment. TRIM32 promotes the attachment of Lys27-linked ubiquitin chains to Lys173 and Lys375 within the ARM domain, which is an autoinhibitory region of SARM1. This ubiquitination by TRIM32 increases SARM1’s NAD+-cleaving catalytic activity and enhances its ability to induce neurite degeneration and cell death. A mutant form of TRIM32 lacking the enzymatically active RING domain fails to promote SARM1 ubiquitination, and reducing TRIM32 levels decreases SARM1 ubiquitination. Additionally, ubiquitin-specific peptidase 13 (USP13), a known negative regulator of SARM1, can deubiquitinate SARM1. These findings suggest that TRIM32 is a key regulator of axon degeneration and cell death through its ubiquitination of SARM1. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0360-3199 270 2026 The effect of end-gas auto-ignition flame properties on the knocking intensity of a dual-fuel hydrogen engine 157103 EN Riku Okamoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nobuyuki Kawahara Faculty of Environmental, Life, Natural Science and Technology, Okayama University Yoshimitsu Kobashi Faculty of Environmental, Life, Natural Science and Technology, Okayama University This study sought to elucidate the mechanism governing PRE-mixed mixture ignition in end-gas region (PREMIER) combustion in a dual-fuel hydrogen engine. Both knocking and PREMIER combustion are induced by end-gas auto-ignition, but differ in terms of the subsequent development of pressure waves. Knocking is accompanied by strong waves, whereas PREMIER combustion is characterized by the absence of, or very few, such waves. End-gas auto-ignition of hydrogen–air mixtures was visualized while in-cylinder pressure was measured using an optical compression and expansion machine. The visualization data indicate that KI increased as the spread velocity of the end-gas auto-ignition front rose. That velocity remained below 100 m/s during PREMIER combustion, but attained approximately 400 m/s in severe knocking cycles. The theory proposed by Bradley was used to evaluate the experimental results, and two dimensionless parameters, ξ and ε, were estimated. The ξ-ε diagram showed a distinct transition from PREMIER combustion to knocking. (150 words). No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0360-3199 270 2026 Synergistic effects of gas-to-liquid pilot ignition and high rates of nitrogen-based simulated EGR on PREMIER combustion in dual-fuel hydrogen engines 157237 EN Nirendra Nath Mustafi Graduate School of Natural Science and Technology, Okayama University Nobuyuki Kawahara Graduate School of Natural Science and Technology, Okayama University Yoshimitsu Kobashi Graduate School of Natural Science and Technology, Okayama University Hydrogen-fueled compression-ignition engines offer a pathway to decarbonize heavy-duty propulsion but face a trade-off between thermal efficiency, NOx emissions, and narrow knock-free windows. Although EGR dilution and pilot-fuel reactivity control have each been studied independently, their combined effect on hydrogen PREMIER (PREmixed Mixture Ignition in the End-gas Region) combustion has not been systematically characterized. This study addresses that gap by comparing diesel and high-cetane Gas-to-Liquid (GTL) pilot fuels in a supercharged hydrogen dual-fuel engine, while varying nitrogen addition to isolate the inert dilution effect of simulated EGR (0–50%). GTL's superior ignitability shortened ignition delay and enhanced combustion stability versus diesel. Increasing inert EGR (nitrogen) dilution suppressed NOx by over 90% (360 to 30 ppm) via reduced peak temperatures, while sustaining knock-free PREMIER combustion and achieving a peak indicated thermal efficiency of 43.55% at ∼0.80 MPa IMEP. Coupling pilot-fuel reactivity control with EGR dilution enables safe, clean, high-efficiency hydrogen dual-fuel. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1616-301X 2026 Biomineral-Inspired Organic/Inorganic Colloidal Liquid-Crystalline Hybrids for Photoresponsive Adhesion e77420 EN Junya Uchida Research Institute for Interdisciplinary Science, Okayama University Ryuta Kiguchi Department of Chemistry and Biotechnology School of Engineering, The University of Tokyo Riki Kato Research Institute for Interdisciplinary Science, Okayama University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Takashi Kato Research Institute for Interdisciplinary Science, Okayama University Bioinspired hybrid nanostructures offer a promising strategy for developing dynamic functional materials. Herein, we report a new class of photoresponsive liquid-crystalline (LC) adhesives based on organic/inorganic nanostructured colloidal hybrids. These LC materials are composed of a biomineral-inspired hydroxyapatite (HAp) nanorod and azobenzene-based forklike molecules. The organic/inorganic LC hybrids exhibit unusual photo-enhanced adhesion upon photoinduced order–disorder phase transitions of these LC materials. The photoresponsive adhesion functions of the colloidal LC hybrids are tuned by spacer moieties of the forklike molecules as well as mixing of the hybrids with the forklike molecules. The reversible photo-enhanced adhesion of the LC hybrids is achieved when the forklike molecule having oligooxyethylene spacers is hybridized with the HAp nanorod. The flexible oligooxyethylene spacers of the forklike molecule are effective for the formation of less ordered packing of the azobenzene units in the LC hybrids, which enables the dynamic photoresponsive functions. We propose an approach to the development of bioinspired photoresponsive LC materials through self-assembly of functional organic molecules and biomineral-based colloidal hybrids. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2059-1381 12 1 2026 Potential effects of intradialytic exercise therapy on physical performance in hemodialysis patients based on the intervention period: a systematic review and meta-analysis 19 EN Daisuke Uchida Department of Internal Medicine, Teikyo University Hospital Mizonokuchi Yu Honda Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine Shigeki Kojima Kojima Kidney and Dialysis Clinic Hiromasa Miyake Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Masatoshi Nishimoto Department of Nephrology, Nara Medical University Akihito Hishikawa Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine Shun Tonomura Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine Tadashi Sofue Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University Naohiko Fujii Department of Nephrology, Hyogo Prefectural Nishinomiya Hospital Masakazu Saitoh Department of Physical Therapy, Faculty of Health Science, Juntendo University Ichiei Narita Niigata Institute for Health and Sports Medicine, Niigata Sports Association Kunihiro Yamagata Department of Nephrology, Institute of Medicine, University of Tsukuba Junichi Hoshino Division of Preventive and Sports Nephrology, Graduate School of Comprehensive Human Sciences, Tokyo Women’s Medical University Hiroo Kawarazaki Department of Internal Medicine, Teikyo University Hospital Mizonokuchi Tsutomu Sakurada Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine Background Intradialytic exercise during hemodialysis (HD) improves physical function and shows high adherence. In Japan, the 2018 guideline by the Japanese Society of Renal Rehabilitation supports intradialytic exercise, but medical insurance only covers the first 90 days. As new studies have emerged since the guideline was published, we conducted a systematic review and meta-analysis to evaluate the impact and optimal duration of exercise interventions beyond 12 weeks.<br> Methods We followed a preregistered protocol (PROSPERO CRD42025642273) and PRISMA-P guidelines. Randomized controlled trials of adult patients undergoing HD performing structured exercise were identified via MEDLINE database (PubMed, March 2017–November 2024) and ICHUSHI-Web database. Two independent reviewers screened studies, extracted data, and assessed risk of bias using Cochrane RoB 2.0. Outcomes included peak oxygen uptake (VO2peak), maximal oxygen uptake (VO2max), 6 min walk distance, timed up and go (TUG) test, handgrip strength, sit-to-stand (STS) performance, and biochemical measures (hemoglobin, standard weekly urea Kt/V [std Kt/V]). Pooled mean differences (MD) with 95% confidence intervals (CI) were calculated using a mixed-effects model (Hartung–Knapp–Sidik–Jonkman method).<br> Results A total of 71 studies, including 43 newly identified studies, were included. Risk of bias was moderate-to-high. Interventions > 12 weeks significantly improved 6 min walking distance (MD 52.4 m [95% CI 35.4–69.3], p < 0.01), VO2peak (MD 3.5 mL/kg/min [95% CI 1.96–5.04], p < 0.01), VO2max (MD 5.29 mL/kg/min [95% CI 2.36–8.22], p < 0.01), hemoglobin (MD 0.94 g/dL [95% CI 0.09–1.78], p = 0.03), and std Kt/V (MD 0.16 [95% CI 0.12–0.20], p < 0.01). TUG (MD −1.68 s [95% CI −2.96 to −0.41], p = 0.02), handgrip strength (MD 4.08 kg [95% CI 1.95–6.22], p < 0.01), and STS performance (MD −2.75 s [95% CI −4.45 to −1.05], p < 0.01) significantly improved in the integrated results of undefined study periods, with nonsignificant trends in studies of > 12 weeks of exercise.<br> Conclusions Our findings suggest that exercise interventions lasting more than 12 weeks can enhance physical performance. Nevertheless, the applicability of these results to older patients remains uncertain, as most evidence is derived from middle-aged cohorts.<br> Trial registration Registered in the PROSPERO database (CRD42025642273). No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-2615 16 15 2026 The Impact of Cold Storage and Seasonality on Raw Cow Milk Microbiota, Assessed by Conventional and Viability PCR 2302 EN Phong Dinh Tran Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takeshi Tsuruta Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Naoki Nishino Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The microbiota of healthy Holstein cow’s milk was analyzed to evaluate the effects of immediate (freezing at the farm: on-site workflow) and delayed processing (freezing after cool transport: laboratory workflow) and to investigate seasonal changes in September, November, and January. Propidium monoazide (PMA) was also used to distinguish between viable and non-viable cells. Microbiota composition differed between the laboratory and the on-site workflow. After cool transport, the abundances of Lactobacillus and Turicibacter increased, while those of Streptococcus, Bradyrhizobium, and Acinetobacter decreased. Based on the β-diversity assessment, the difference between viable and non-viable cells was marginal compared with the difference between on-site and laboratory workflows. In the subsequent on-site workflow experiment, seasonal variation was clearly demonstrated. The relative abundances of Lactobacillus, Turicibacter, and Bacillus were high in September; Staphylococcus, Phenylobacterium, and Bradyrhizobium in November; and Phyllobacterium in January. The seasonal effect was greater than the PMA treatment effect. Despite the study’s limitations, such as a limited number of milk samples and data from only one farm with a single management system, our findings indicate that storage and transport at low temperatures could lead to inaccurate assessments, particularly of opportunistic environmental microbiota. Viability PCR could help improve our understanding of the factors involved but would not substantially alter the raw milk microbiota. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1386-1425 359 2026 Discrimination of nanovesicles using two-color laser-induced fluorescence detection 127928 EN Shunsuke Asahi Department of Chemistry, Okayama University Takashi Kaneta Department of Chemistry, Okayama University A two-color fluorescence-detection system was developed to distinguish between two types of nanovesicles labeled with different fluorescent dyes. This system employs two lasers emitting at distinct wavelengths (488 and 635 nm). These lasers are reshaped into sheet-like beams and focused at separate positions within a square capillary. As vesicles flow through the capillary, they pass through the laser beams and emit fluorescence when excited by the corresponding wavelength. This technique allows for the counting of vesicles and identification of the specific fluorophores on the vesicles based on their emission positions. The system was validated using liposomes labeled with fluorophores excited by the 488 and 635 nm lasers. It was then applied to differentiate CD63-positive extracellular vesicles (EVs) from other types of EVs in a culture media consisting of HeLa and A549 cells. Additionally, the system was used to study the effect of the anticancer drug doxorubicin on EV secretion in these cancer cells. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 18 10 2026 Racial/Ethnic Disparities in Neoplasm-Related Mortality and the Social Determinants of Health 1572 EN Yoshito Nishimura Division of Hematology, Mayo Clinic Mariko Fujii Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nanami Sako Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Quynh Thi Vu Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ko Harada Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital, Urshila Durani Division of Hematology, Mayo Clinic Stephen M. Ansell Division of Hematology, Mayo Clinic James R. Cerhan Department of Quantitative Health Sciences, Mayo Clinic Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Racial/ethnic and regional disparities in neoplasm-related mortality remain a significant public health challenge. In this study, we aimed to evaluate long-term trends in county-level neoplasm-related mortality rates by race/ethnicity in the United States and examine associations with social determinants of health. Methods: We conducted a cross-sectional ecological study using population-based data from the Global Burden of Disease Study, including individuals residing in 50 states of the United States and the District of Columbia from 2000 to 2019. We analyzed age-standardized neoplasm-related mortality rates by ethnicity/race. Joinpoint regression analysis was used to identify significant changes in mortality trends, summarized as average annual percentage change. County-level correlations between mortality and key social determinants of health were also assessed. Results: Neoplasm-related mortality rates declined across all racial/ethnic groups from 2000 to 2019; however, disparities persisted. The age-standardized neoplasm-related mortality rates per 100,000 population decreased in all racial/ethnic subgroups. The average annual percentage change ranged from −0.94% (Hispanic and non-Hispanic American Indian or Alaska Native) to −1.90% (Black). Sex-specific analyses revealed similar trends. Southeastern states experienced slower declines than Northeastern states did. County-level smoking and poverty rates were positively correlated, whereas the primary care physician-to-population ratio, excessive alcohol consumption rate, mammography screening rate, and median household income were inversely correlated with neoplasm-related mortality rate, varying by race/ethnicity. Conclusions: Targeted, community-specific interventions are required to reduce inequities in cancer outcomes. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1356-9597 31 5 2026 Transforming Life Science Through Chromosome‐Level Genome Assemblies e70145 EN Tetsuo Kon Department of Neurosciences and Developmental Biology, University of Vienna Kosuke Kataoka Graduate School of Engineering, Tokyo University of Agriculture and Technology Yi‐Jyun Luo Biodiversity Research Center, Academia Sinica Johannes Nicolaus Wibisana Genomics and Regulatory Systems Unit, Okinawa Institute of Science and Technology Graduate University Kouhei Toga Laboratory of BioDX, PtBio Co‐Creation Research Center, Genome Editing Innovation Center, Hiroshima University Narumi Uno Laboratory of Bioengineering, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences Yuki Monden Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Mayuko Hamada Ushimado Marine Institute, Okayama University Advances in long-read sequencing and Hi–C scaffolding have made chromosome-level genome assembly increasingly accessible to individual laboratories, shifting genome research from large consortium-led projects toward investigator-driven studies across diverse taxa. This transition allows researchers to select organisms based on biological questions rather than the prior availability of genomic resources. In this review, we summarize the core experimental and computational steps for generating, evaluating, and annotating chromosome-level assemblies, and examine how they have advanced research in non-model organisms and genetically complex systems. Representative case studies illustrate four major contributions: resolving structural variation and lineage-specific genome architecture, linking genome organization to phenotypic innovation and plasticity, reconstructing deep chromosome evolution and macrosynteny, and distinguishing homologous and homoeologous chromosomes in polyploid genomes. These examples show that chromosome-level assemblies provide more than complete reference sequences. They establish a continuous genomic coordinate system through which genes, regulatory elements, transposable element insertions, sequence variants, and cellular states can be interpreted within broader chromosomal, population, and evolutionary contexts. We describe this integrative perspective as “glocal biology.” Future progress will require pangenomic, population-scale, and haplotype-resolved resources integrated with multi-omics and functional analyses. Collectively, chromosome-level genomics is reshaping life science by embedding molecular functions within chromosomal and evolutionary contexts. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2699-9307 6 6 2026 NUAK2 Inhibition Enhances Macromolecular Drug Delivery in a 3D Fibrotic Model of the Pancreatic Tumor Microenvironment e202500237 EN Misaki Nakamura Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hiroyoshi Y. Tanaka Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Mayu Ohira 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 Reika Nakamura Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Yu Seno Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Saaya Yara Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Sakura Fujita Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Daichi Shibata Department of Pharmaceutical Biomedicine Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Masaya Yamamoto Department of Materials Processing Graduate School of Engineering, Tohoku University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Kensuke Osada Department of Molecular Imaging and Theranostics Institute for Quantum Medical Science, National Institutes for Quantum Sciences and Technology (QST) 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 Pancreatic ductal adenocarcinoma (PDAC) features a fibrotic tumor microenvironment that impedes drug delivery and significantly limits the successful clinical application of nanomedicines. Targeting signaling in pancreatic stellate cells (PSCs), which drive fibrosis via excessive secretion of extracellular matrix proteins such as collagen I, may be useful in overcoming this fibrotic barrier. The AMPK-related kinases NUAK1/2 have recently gained interest as promoters of fibrosis, but whether they play a profibrotic role in PSCs remains unknown. Here, patient PSCs are used to assess NUAK1/2 involvement in the PDAC fibrotic barrier. Leveraging a 3D cell culture model of PDAC fibrosis, the effect of targeting NUAK1/2 on the permeability of macromolecular dextrans of various sizes, as well as physiologically relevant macromolecules, albumin and IgG, and clinical nanomedicines, Doxil and Abraxane, is investigated. NUAK1/2 inhibition is shown to diminish collagen I to enhance macromolecular permeability, via a mechanism independent of established pathways involving transforming growth factor-β (TGFβ) and yes-associated protein (YAP). Through isoform-specific knockdown, predominant NUAK2 involvement is demonstrated. Mechanistically, actin stress fiber regulation by NUAK2 is shown to be important. Altogether, these results show in vitro that NUAK2 promotes fibrotic signaling in PSCs 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 2056-306X 12 1 2026 Knockout analysis of period and timeless and EGFP-based visualization of per-expressing clock cells in the cricket circadian clock 12 EN Kenji Tomioka Graduate School of Natural Science and Technology, Okayama University Shintaro Inoue Bio-Innovation Research Center, Tokushima University Taro Mito Bio-Innovation Research Center, Tokushima University Yoshiyuki Moriyama Department of Natural Sciences, Kawasaki Medical School Taishi Yoshii Graduate School of Environmental, Life, Natural Science and Technology, Okayama University In the present study, we generated crickets with knockout of either period (per) or timeless (tim) gene by CRISPR/Cas9-based genome editing. We also identified a naturally occurring per- mutant lacking a large coding region including PAS domains. To examine possible synergistic effects, a per- and timKO double mutant was generated by applying genome editing to the per- crickets. Under constant darkness (DD), timKO crickets exhibited a locomotor rhythm with a free-running period of 23.06 ± 0.20 h (mean ± SD), which was significantly shorter than that of the parental strain (23.78 ± 0.12 h). By contrast, perKO and per- crickets showed basically similar phenotype of locomotor rhythm: they exhibited an arrhythmic pattern during the first two to three weeks after transfer to DD but subsequently showed a complex rhythmic pattern with one or multiple components with significantly longer free-running periods (33.35 ± 10.72 h). In the per-;timKO double mutants, approximately 60% of individuals became arrhythmic, while the remaining 40% exhibited complex rhythms with extremely longer free-running periods (37.0 ± 9.17 h) under DD. These results suggest the existence of an underlying oscillatory mechanism that is responsible for regulating locomotor rhythms independently of the canonical per/tim feedback loop. Furthermore, we generated a reporter line on a per− background by knocking egfp into exon 1 of the per gene, allowing egfp expression to report per transcription. EGFP expression was detected in three distinct clusters of cells within the optic lobe: two located along the dorsal and ventral boundaries between the lamina and medulla neuropils, and one situated near the accessory medulla. These findings raise the possibility that these form part of the circadian clock network that governs circadian locomotor rhythms. No potential conflict of interest relevant to this article was reported.

公益社団法人 日本放射線技術学会 Acta Medica Okayama 0369-4305 82 10 2026 ベイズ推定を用いたラジオクロミックフィルムのADC値–線量変換法 26-1707 EN Yuki Tanimoto Department of Radiology, NHO Iwakuni Clinical Center Kohei Sugimoto Department of Radiological Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare Masahide Tamori Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center Miho Yatsuki Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center Shohei Yoshida Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center Kazuma Sugahara Department of Radiology, NHO Kure Medical Center and Chugoku Cancer Center Masataka Oita Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University 【目的】ラジオクロミックフィルムは高い空間分解能を有することから，患者別IMRT品質保証（IMRT QA）に広く利用されている．一方，ピクセル値を線量へ変換するためのキャリブレーションには，複数の既知線量で照射したフィルムが必要であり，作業負担が大きいことから，施設によってはフィルムロット変更時などに限定して実施される場合がある．本研究では，過去のキャリブレーションデータセットと対象フィルムの未照射時ピクセル値を用いてキャリブレーション曲線を推定するベイズ推定モデルを構築し，キャリブレーション作業の効率化を目的としてその有用性を検証した．【方法】TomoHDを用いて取得した93組のキャリブレーションデータセットを解析対象とした．線量および照射からスキャンまでの経過時間を説明変数とする二次多項式回帰モデルを構築した．モデルはスキャナの読み取り方向（縦方向・横方向）ごとに作成し，対象フィルムの未照射時ピクセル値を切片項として推定した．ベイズ推定にはStanを用い，トレースプロットおよびRhat統計量により収束性を評価した．更にモデル性能の評価には，異なるロットのEBT4フィルム10枚を用いて予測ピクセル値と実測値を比較するとともに，線量誤差を評価した．【結果】すべてのモデルでRhatは1.01未満を示し，良好な収束性が確認された．検証用フィルムでは，ピクセル値の誤差は3.6%未満，決定係数（R2）は0.99以上であった．また，線量誤差は24 cGyで平均2.7 cGy（SD 1.3），868.2 cGyで平均37.5 cGy（SD 12.8）であり，最大線量誤差は710.6 cGyにおいて66.6 cGyであった．【結語】本手法は，過去のキャリブレーションデータセットと対象フィルムの未照射時ピクセル値を用いてキャリブレーション曲線を推定できる可能性を示した．また，ラジオクロミックフィルムのキャリブレーション作業の効率化に寄与する可能性が示唆された．今後は患者別IMRT QAに適用し，線量分布評価への影響を検証する必要がある． No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0960-7412 127 3 2026 AHG1–AFP interaction as a regulatory node in the ABA response during seed germination e71081 EN Noriyuki Nishimura Institute of Agrobiological Sciences, National Agriculture and Food Research Organization Sho Ushiyama Institute of Plant Science and Resources, Okayama University Masato Otagiri Institute of Plant Science and Resources, Okayama University Kouji Satoh Institute of Agrobiological Sciences, National Agriculture and Food Research Organization Nahomi Suzuki Institute of Agrobiological Sciences, National Agriculture and Food Research Organization Tomoko Irisa Institute of Agrobiological Sciences, National Agriculture and Food Research Organization Nobutaka Mitsuda Biomanufacturing Process Research Center, National Institute of Advanced Industrial Science and Technology Taishi Umezawa Graduate School of Advanced Interdisciplinary Science, Tokyo University of Agriculture and Technology Hideki Nishimura Institute of Plant Science and Resources, Okayama University Keiichirou Nemoto Proteo-Science Center, PIAS, Ehime University Wataru Tsuchiya Research Center for Advanced Analysis, National Agriculture and Food Research Organization Ryoichi Yano Research Center for Advanced Analysis, National Agriculture and Food Research Organization Tatsuya Sawasaki Proteo-Science Center, PIAS, Ehime University Toshimasa Yamazaki Research Center for Advanced Analysis National Agriculture and Food Research Organization Tsukuba Ibaraki 305‐8518 Japan Takashi Hirayama Research Center for Advanced Analysis, National Agriculture and Food Research Organization Seed dormancy and germination are tightly regulated by complex signaling networks that integrate internal and external cues, including the endogenous phytohormone abscisic acid (ABA). ABA HYPERSENSITIVE GERMINATION 1 (AHG1), a group A type 2C protein phosphatase (PP2C), is thought to modulate the activity of transcription factors such as ABA INSENSITIVE 5 (ABI5) in seeds and during germination. AHG1 is regulated by DELAY OF GERMINATION 1 (DOG1), a key regulator of seed dormancy, through physical interaction. We previously reported that AHG1 also interacts with ABI FIVE BINDING PROTEIN 2 (AFP2), a member of the AFP family; however, the molecular basis of AHG1–AFP coordination has remained unclear. In this study, we show that AHG1 interacts with all AFP family members and that AFP3 binds AHG1 and ABI5 through adjacent but distinct amino acid residues within its C-domain, allowing simultaneous association with both proteins. In addition, AHG1 modulates the phosphorylation status of AFP3 at Ser60 in a DOG1-dependent manner, suggesting that DOG1–AHG1 regulates AFP3 post-translationally. Transcriptomic analyses of AHG1- or AFP3-overexpressing lines revealed that these factors are associated with the regulation of a shared set of ABA-responsive genes, including AFPs, and that AFP3 overexpression is predominantly associated with altered expression of genes involved in transcriptional regulation. Large-scale protein interaction analyses showed that AFPs interact with multiple classes of transcription factors, suggesting their involvement in diverse regulatory pathways, including ABA signaling. Together, these findings demonstrate that DOG1 regulates ABI5 function and modulates ABA responses, at least in part, by controlling AHG1-mediated dephosphorylation of AFPs. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0016-6480 384 2026 Alternative transcription of the mouse Gh gene identifies an immune-associated transcript with species-specific structural divergence 114996 EN Ai Fukushima Graduate School of Natural Science and Technology, Okayama University Yu Takeuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hibiki Fukuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sakura Egoshi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hirotaka Sakamoto Graduate School of Natural Science and Technology, Okayama University Sayaka Aizawa Graduate School of Natural Science and Technology, Okayama University Sakae Takeuchi Graduate School of Natural Science and Technology, Okayama University Growth hormone (GH) in mice is primarily expressed in the anterior pituitary, although Gh expression has been reported in extrapituitary tissues, including immune organs. However, the structure of immune-associated Gh transcripts remains poorly characterized. To determine whether splenic Gh transcripts differ from pituitary Gh mRNA, 5′- and 3′-rapid amplification of cDNA ends (RACE) analyses were performed. While 3′ RACE showed a shared polyadenylation site, 5′ RACE identified a novel exon located approximately 2 kb upstream of the conventional exon 1, generating a transcript (spl-Gh mRNA) with a distinct first exon but shared downstream exons with pituitary Gh mRNA (pit-Gh mRNA). RT-PCR analysis revealed that spl-Gh mRNA is predominantly expressed in immune tissues such as spleen and bone marrow, and its distribution did not correlate with Pit-1 mRNA expression. Quantitative RT-PCR further demonstrated that spl-Gh mRNA was expressed at levels comparable to those of pit-Gh mRNA in the mouse spleen, indicating that spl-Gh is one of the major Gh transcript forms in this tissue. Sequence analysis indicated that spl-Gh mRNA is predicted to retain coding potential for a GH protein. Comparative genomic analyses further demonstrated that genomic features associated with the spl-Gh transcriptional unit are conserved only in a subset of closely related Mus species. In contrast, although a spl-Gh–related transcript was detected in rat spleen, no properly spliced mouse-like transcript was identified under the present experimental conditions. The detected transcript exhibited intron retention and an in-frame stop codon, suggesting that it is unlikely to produce a functional GH protein. These findings identify a distinct immune-associated Gh transcript generated through alternative transcription of the mouse Gh gene and suggest that immune-associated Gh transcriptional mechanisms have undergone species-specific divergence among rodents. Together, these findings reveal previously unrecognized complexity in Gh gene regulation and highlight species-specific differences in immune-associated Gh transcripts. No potential conflict of interest relevant to this article was reported.

AIP Publishing Acta Medica Okayama 0021-9606 165 7 2026 High-resolution analysis of the S1–S0 transition of magnesium phthalocyanine: Rotational structure and electronic angular momentum 074308 EN Yuki Miyamoto Research Institute for Interdisciplinary Science, Okayama University Katsunari Enomoto Department of Physics, University of Toyama Kana Iwakuni Institute for Laser Science, University of Electro-Communications Susumu Kuma Department of Physics, Rikkyo University Koichi M. T. Yamada Institute for Laser Science, University of Electro-Communications We report a high-resolution spectroscopic analysis of the S1–S0 transition of magnesium phthalocyanine (MgPc), obtained by probing buffer-gas-cooled molecules with a narrow-linewidth laser. The observed spectrum exhibits a characteristic three-peak pattern, which is well reproduced by modeling MgPc as an oblate symmetric top with D4h symmetry. A key result of this work is that the spectrum is strongly influenced by electronic Coriolis coupling, which is associated with electronic angular momentum. The electronic Coriolis constant is determined to be ∼2, indicating an effective orbital angular momentum of about 2 in the excited S1 state, originating from the π-conjugated ring excitation. This provides a direct spectroscopic signature of electronic angular momentum in a large polyatomic molecule. The presence of nonzero electronic orbital angular momentum is qualitatively consistent with the perimeter model of phthalocyanines. The value lies within the range inferred from previous magnetic circular dichroism (MCD) studies. Compared with the previous MCD estimate, the present analysis provides a more state-specific and narrower constraint, demonstrating that high-resolution spectroscopy enables direct access to electronic and magnetic properties beyond conventional structural characterization. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 15 13 2026 Changing Trends in Cardiovascular Disease Burden in North Africa and the Middle East, 1990–2023: A Joinpoint Analysis of GBD 2023 Data 4866 EN Hanane Ouddoud Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Judah Israel Ong Lescano Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Keith Pardillada Belangoy Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yoshito Nishimura Division of Hematology and Oncology, Mayo Clinic Ko Harada Division of Hematology and Oncology, Mayo Clinic Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Quynh Thi Vu Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Naohiro Iwata Department of Pharmacy, Okayama University Hospital Tatsuaki Takeda Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background/Objectives: Cardiovascular disease (CVD) burden decreased in the North Africa and Middle East (NAME) region between 1990 and 2019. This study used Global Burden of Disease (GBD) 2023 data to examine whether trends in mortality, disability-adjusted life years (DALYs), incidence, and prevalence continued through 2023 across all 21 NAME countries. Methods: We analysed age-standardised CVD mortality, incidence, prevalence, and DALY rates from 1990 to 2023. Joinpoint regression identified changes in temporal trends and calculated the annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals (CIs). Results: Age-standardised CVD mortality decreased from 579.6 per 100,000 in 1990 to 358.2 in 2023 (AAPC: −1.42%; 95% CI: −1.48 to −1.35). However, no significant reduction occurred between 2019 and 2023 (APC: −0.33%; 95% CI: −1.37 to 1.75). DALY, incidence, and prevalence rates followed similar patterns, with no significant decline in the final years of this study. Egypt was the only country with a long-term increase in CVD mortality, which accelerated after 2020 (APC: +5.20%; 95% CI: 1.20 to 12.87). High systolic blood pressure, dietary risks, lead exposure, and air pollution were the leading modifiable risk factors. Conclusions: The earlier decline in CVD burden in the NAME region did not clearly continue after 2019. The region is currently off track to meet Sustainable Development Goal 3.4 by 2030. Future progress may depend on improved blood pressure control, lipid management, dietary habits, and environmental risk reduction. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2399-3642 8 1 2025 Structural insights into tRNA recognition of the human FTSJ1-THADA complex 893 EN Kensuke Ishiguro Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research Atsushi Fujimura Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mikako Shirouzu Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research tRNA undergoes various post-transcriptional modifications in the anticodon loop. FTSJ1, a protein conserved among most eukaryotes, mediates 2’-O-methylations at position 32 (Nm32) or position 34 (Nm34), complexed with THADA or WDR6, respectively. These methylations are crucial for accurate translation and cellular growth. FTSJ1 mutations are associated with non-syndromic X-linked intellectual disability. Although the structure of the FTSJ1-WDR6 complex in yeast has been solved, the structural details of the FTSJ1-THADA complex formation and substrate recognition remain unclear. Herein, using cryo-electron microscopy, we solve the high-resolution structure of FTSJ1-THADA with or without a tRNA substrate. FTSJ1 binds to THADA via its C-terminal region, with a unique interaction mode distinct from the FTSJ1-WDR6 complex. The tRNA substrate is anchored inside THADA, and key THADA residues for THADA-tRNA interaction are identified via structural and biochemical analyses. These findings demonstrate how FTSJ1 and THADA form a complex to mediate Nm32 modification in various tRNAs. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 2226-7190 13 3 2024 Hormonal changes revealed by selective arterial calcium injection tests in patients with insulinoma treated with EUS–guided ethanol injection 193 195 EN Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Motoshi Komatsubara Department of Endocrinology, Okayama City Hospital Kenichi Inagaki Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Hospital Motoyuki Otuka Department of Gastroenterology and Hepatology, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1356-9597 30 3 2025 Polished Rice Regulates Maturation but Not Survival of Secondary Cells in Drosophila Male Accessory Gland e70025 EN Shinichi Otsune Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mirai Matsuka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Chisato Shirakashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Xuanshuo Zhang Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hideki Nakagoshi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University In Drosophila males, the accessory gland is responsive to nutrient signal-dependent regulation of fertility/fecundity. The accessory gland is composed of two types of binucleated epithelial cells, about 1000 main cells and 60 secondary cells (SCs). The transcription factors Defective proventriculus (Dve), Abdominal-B, and Ecdysone receptors (EcRs) are strongly expressed in adult SCs. In response to nutrient conditions during development, coordinated action between Dve and ecdysone signaling determines the optimal number of SCs and regulates their maturation. A downstream effector of ecdysone signaling, Ftz-F1, is crucial in this process. Another downstream effector, Polished rice (Pri), is small peptides of 11 or 32 amino acids. Here we show that pri is required for maturation of SCs and for male fecundity, whereas it is not involved in determination of the number of SCs. We provide evidence that Pri acts downstream of Ftz-F1 to regulate maturation but not survival of SCs. 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 Amyloid-forming property of the N-terminal 1−70 residues of human apolipoprotein A-IV 13203 EN Norihiro Namba Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University Tokiko Danjo Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University Yuichiro Kitagawa Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University Yoshito Naito Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University Takashi Ohgita Center for Instrumental Analysis, Kyoto Pharmaceutical University Toshinori Shimanouchi Graduate School of Environmental and Life Science, Okayama University Hiroyuki Saito Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University Apolipoprotein A-IV (apoA-IV), the largest member of the exchangeable apolipoprotein family, is a common constituent of amyloid deposits in renal and cardiac amyloidosis. In this study, we characterized the aggregation propensity of the apoA-IV N-terminal fragment to form amyloid fibrils using a variety of biophysical techniques. Thioflavin T fluorescence assay, circular dichroism measurement, and microscopic observations revealed that the N-terminal 1−70 amino acid fragment of apoA-IV readily forms amyloid fibrils by a transition from a random coil to a β-sheet-rich structure. Sequence-based analysis indicated that residues 7−16 and 38−42 are the major aggregation-prone segments within the N-terminal 1−70 residues of apoA-IV. Consistent with this, deletion of these residues strongly inhibited the β-transition and fibril formation of apoA-IV 1−70. Kinetic and thermodynamic analyses of fibril formation by the apoA-IV 1−70 fragment demonstrated that primary nucleation is the dominant step in fibril formation, for which the activation energy barrier is entirely entropic. In addition, we found that the presence of heparin, a representative glycosaminoglycan, accelerated fibril formation kinetics and enhanced the yield of apoA-IV 1−70 fibrils, and the positively charged residues K58-K59 play a critical role in heparin interaction. Overall, our results suggest that the strong amyloid-forming propensity of the N-terminal fragment of apoA-IV may play a key role in amyloid deposition associated with apoA-IV amyloidosis. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 2296-634X 14 2026 Prolonged TNF-α stimulation induces a PD-1–associated exhaustion-like phenotype in mesenchymal stromal cells 1680076 EN Naoya Matsunaga Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Akiyama Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aung Ye Mun Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tinling Zou Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Ito Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ruji Tagashira Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuo Kuboki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mesenchymal stromal cells (MSCs) have emerged as promising therapeutic agents for inflammatory diseases because of their potent immunomodulatory properties. Although acute inflammation transiently enhances MSC functionality, the impact of chronic inflammatory exposure remains poorly defined. In this study, we investigated the effects of sustained TNF-α stimulation and indirect co-culture with M1 macrophages on MSC behavior. Comprehensive gene expression profiling was performed to assess the changes in immunoregulatory, apoptotic, and metabolic pathways. To determine functional reversibility, we also evaluated MSCs following the withdrawal of TNF-α. Short-term exposure led to upregulation of Tgf-β, Il-10, and Fasl, whereas prolonged stimulation suppressed these genes and significantly increased the expression of immune checkpoint genes Pd-1 and Ctla-4, indicative of an exhaustion-like phenotype. This phenotypic shift was associated with sustained NF-κB activation, upregulation of Stat3 and Ap-1, suppression of mTORC1/2 components, decreased Pd-l1 expression, and increased Pd-1 expression, raising the possibility that PD-1 upregulation is associated with MSC dysfunction under chronic inflammatory stress. These findings revealed that prolonged stimulation (48 h) induces an exhaustion-like dysfunction state in MSCs, characterized by checkpoint activation, transcriptional repression, and metabolic dysfunction. PD-1 may serve as a biomarker associated with inflammation-induced MSC impairment. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1648-9144 62 7 2026 Diabetes Burden in the Middle East and North Africa Region, 1990–2023: An Ecological Time-Trend Analysis of GBD Estimates 1352 EN Hanane Ouddoud Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Judah Israel Ong Lescano Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Keith Pardillada Belangoy Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yoshito Nishimura Division of Hematology and Oncology, Mayo Clinic Ko Harada Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Quynh Thi Vu Faculty of Pharmacy, Haiphong University of Medicine and Pharmacy Naohiro Iwata Department of Pharmacy, Okayama University Hospital Tsukasa Higashionna Department of Pharmacy, Okayama University Hospital Tatsuaki Takeda Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background and Objectives: The Middle East and North Africa (MENA) region has one of the highest age-standardized diabetes prevalence rates globally, yet all-age, diabetes-specific evidence incorporating GBD 2023 estimates through 2023 remains limited. Materials and Methods: Using Global Burden of Disease (GBD) 2023 estimates for 21 MENA countries from 1990 to 2023, this ecological time-trend analysis quantified 33-year trends in incidence, prevalence, mortality, and disability-adjusted life-years (DALYs); compared pre-2019 and post-2019 trajectories using joinpoint regression; characterized age- and sex-specific burden patterns; and quantified contributions of modifiable risk factors. Results: Age-standardized incidence increased 92%, from 251.7 (95% uncertainty interval [UI]: 231.5 to 272.4) to 482.5 (95% UI: 451.5 to 516.4) per 100,000, and prevalence more than doubled, from 5564 (95% UI: 5088 to 6024) to 11,247 (95% UI: 10,382 to 12,132) per 100,000. In 2023, males exhibited higher DALY rates than females in most adult age groups from age 15 years onward, shifting away from the female-predominant pattern seen in 1990; female rates remained higher at several of the oldest age groups. Children aged 0 to 14 years were the only group with declining DALY rates (−52% to −57%). Post-2019 incidence was higher in 15 of 21 countries, and six countries had higher DALY trends with non-overlapping confidence intervals. Because we only have four to five years of data, these short trends are preliminary and require care when evaluating. High body-mass index was the leading modifiable risk factor. Conclusions: These data support country-specific prevention and chronic-care strategies across the MENA region. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1467-7644 2026 Identification of Critical Amino Acid Residues Required for the Polar Localization of a Rice Manganese Transporter EN Noriyuki Konishi Institute of Plant Science and Resources, Okayama University Jian Feng Ma Institute of Plant Science and Resources, Okayama University Rice has developed an efficient system for manganese (Mn) uptake, mediated by two distinct transporters, OsNramp5 and OsMTP9. These transporters exhibit polar localization at the root exodermis and endodermis; however, the mechanisms underlying their polar localization and their role in Mn uptake remain unclear. Here, we identified key amino acid residues critical for the polar localization of OsNramp5 at the distal side. Through analysis of chimeric proteins between OsNramp5 and its non-polar homologues, we found that the C-terminal cytosolic region of OsNramp5 is essential for its polar localization. Site-directed mutagenesis further revealed that aspartate 500 and four valine residues at positions 494, 495, 498 and 506 are crucial for polarity. Substitution of these valine residues with isoleucine, leucine, phenylalanine, or threonine partially or fully maintained polar localization, whereas substitution with alanine, serine, or asparagine resulted in loss of polarity. These findings suggest that β-branching and high hydrophobicity of amino acid side chains are likely required for OsNramp5 polarity. Furthermore, we found that adaptor protein 2-dependent clathrin-mediated endocytosis is not involved in the polar localization of OsNramp5. Finally, we provided experimental evidence showing the significant role of OsNramp5 polarity in efficient Mn uptake in rice; plants expressing non-polarly localized OsNramp5 exhibited reduced Mn uptake compared to those with polarly localized OsNramp5. In addition, we found that cadmium accumulation in shoots could be reduced by manipulating OsNramp5 polarity in combination with its overexpression, without a growth penalty. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0001-8686 358 2026 Revisiting particle formation beyond classical nucleation: A unified classification framework for nonclassical pathways 104018 EN Yuya Iida Faculty of Environmental, Life, Natural Science and Technology, Okayama University Satoshi Watanabe Department of Chemical Science and Engineering, Kyoto University Particle formation is pervasive in both nature and technology, shaping environmental and biological phenomena while underpinning a broad range of industrial products. A mechanistic understanding of particle formation is therefore important both for fundamental science and for the design of particle properties. It is now well established that particle formation can proceed through diverse pathways beyond classical one-step nucleation. At the same time, the proliferation of reported nonclassical pathways has blurred the distinctions among mechanistic categories and obscured their underlying relationships. In this review, we revisit the development of concepts in particle formation pathways and present a unified perspective on this increasingly complex mechanistic landscape. To this end, we classify the nonclassical features of particle formation along three conceptual axes: stepwise transitions between phases or phase-like fluctuations, chemically driven formation of structural units, and aggregation-dominant nucleation and growth processes. This framework places diverse pathways within a common three-dimensional space referenced to classical nucleation, providing a basis for comparing apparently distinct mechanisms within a single picture. We further discuss representative theoretical descriptions in relation to these axes and outline future challenges. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2452-302X 10 10 2025 Inhibition of Scarb1 on Endothelial Cells Attenuates Pressure Overload-Induced Heart Failure Progression 101308 EN Toshiomi Katsuki Department of Cardiology, Keio University School of Medicine Dai Kusumoto Department of Cardiology, Keio University School of Medicine Yohei Akiba Department of Cardiology, Keio University School of Medicine Mai Kimura Department of Cardiology, Keio University School of Medicine Jin Komuro Department of Cardiology, Keio University School of Medicine Takahiro Nakamura Department of Cardiology, Keio University School of Medicine Hisayuki Hashimoto Department of Cardiology, Keio University School of Medicine Thukaa Kouka Department of Cardiology, Keio University School of Medicine Kazuhisa Sugai Institute for Integrated Sports Medicine, School of Medicine, Keio University Yoshinori Katsumata Department of Cardiology, Keio University School of Medicine Masaki Miyasaka Department of Computational Biology and Medical Sciences, the University of Tokyo Yutaka Suzuki Department of Computational Biology and Medical Sciences, the University of Tokyo Junko Kuramoto Department of Pathology, Keio University School of Medicine Yoshiaki Kubota Department of Anatomy, Keio University School of Medicine Keiichi Fukuda Department of Cardiology, Keio University School of Medicine Shinsuke Yuasa Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaki Ieda Department of Cardiology, Keio University School of Medicine Inappropriate endothelial cell (EC) interactions contribute to heart failure; however, their precise mechanisms remain poorly understood. This study investigated EC-fibroblast interactions mediated by Scarb1 using single-cell RNA-sequencing analysis in a mouse heart failure model. ECs exhibited inflammatory and fibrotic gene expression, with Scarb1-mediated fibroblast-EC interactions driving disease progression. EC-specific Scarb1 knockout and systemic SCARB1 inhibition attenuated heart failure progression. In vitro and spatial omics analyses confirmed the role of SCARB1 in ECs and cell-cell interaction during heart failure progression. These findings highlight SCARB1 as a promising therapeutic target for EC-focused interventions. 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 Novel Approximate Solution Method for Euclidean Steiner Tree Problem Based on Genetic Algorithm 122947 122962 EN Liping Zhang Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tsuyoshi Migita Faculty of Environmental, Life, Natural Science and Technology, Okayama University Norikazu Takahashi Faculty of Environmental, Life, Natural Science and Technology, Okayama University A novel approximate solution method for the Euclidean Steiner tree problem is proposed and its performance is demonstrated through experiments using 195 benchmark problem instances from the OR-Library. Given a finite number of terminal points, the proposed method first generates non-terminal points around each terminal point and at the same location as the Steiner point for each triangle obtained by the Delaunay triangulation for all terminal points. It next runs a genetic algorithm to select a subset of the generated non-terminal points, aiming to minimize the total edge length of a minimum spanning tree for all the terminal points and the selected non-terminal points. It then optimizes the locations of the non-terminal points in the tree using Weiszfeld’s method, while preserving the topology. It finally refines the tree by adding new non-terminal points, adding and removing edges, and optimizing the locations of all non-terminal points. The experimental results show that, among 150 benchmark problem instances with known optimal solutions, the proposed method successfully constructs a Euclidean Steiner tree for 61 instances. For the remaining 89 instances, it produces an approximate solution whose total edge lengths is less than 100.7% of the optimal. The experimental results also show that the proposed method obtains approximate solutions efficiently: within 1.5 seconds for instances with up to 100 terminal points and within 61 seconds for instances with up to 1,000 terminal points. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 2169-9313 131 8 2026 Effect of Fluorine on the Stability of Dense Hydrous Mg Silicates With Implications for the Deep Water Cycle e2025JB033593 EN Takashi Yoshino Institute for Planetary Materials, Okayama University Yunfan Miao Institute for Planetary Materials, Okayama University Satheesh T. Saji Institute for Planetary Materials, Okayama University Daijo Ikuta Institute for Planetary Materials, Okayama University Nozomi Kondo Institute for Planetary Materials, Okayama University Takayuki Ishii Institute for Planetary Materials, Okayama University Xuejing He Geochemical Research Center Graduate School of Science, The University of Tokyo Tsutomu Ota Institute for Planetary Materials, Okayama University Takuya Kunihiro Institute for Planetary Materials, Okayama University Water is believed to be transported, at least locally, into the Earth's deep mantle via hydrous minerals. Fluorine not only tends to interact with water but also influences the stability of hydrous minerals. Thus, knowledge of its stability could be important in understanding the deep-water cycle. In this study, we conducted high-pressure experiments to investigate the stability of dense hydrous Mg silicates in the presence of fluorine at pressures ranging from 9 to 23 GPa. In the presence of even small amounts of fluorine, clinohumite or phase E survives up to approximately 17 GPa, allowing it to exist without dehydration at temperatures by about 200°C higher than a fluorine-free system. At pressures above 18 GPa, superhydrous phase B stabilizes as a major fluorine host. Fluorine partitions very little into phase D, leaving its stability field unchanged, but the stability field of superhydrous phase B extends to temperatures above 1400°C, thereby enabling the hydrous phase in the dragged wedge mantle just above the slab to have transport potential into the lower mantle. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 2169-9313 131 8 2026 Spin Transition of Ferric Iron in Silicate Glasses Inferred by High‐Pressure Electrical Conductivity Measurements e2026JB034225 EN Izumi Mashino Institute for Planetary Materials, Okayama University Takashi Yoshino Institute for Planetary Materials, Okayama University Shinji Kitao Institute for Integrated Radiation and Nuclear Science, Kyoto University Takaya Mitsui Synchrotron Radiation Research Center, Kansai Photon Science Institute, Quantum Beam Science Research Directorate, National Institutes for Quantum Science and Technology Ryo Masuda Graduate School of Science and Technology, Hirosaki University Makoto Seto Institute for Integrated Radiation and Nuclear Science, Kyoto University Silicate melt has been proposed to exist near the base of the mantle and has been invoked to explain seismic and electrical conductivity anomalies observed near the core-mantle boundary; however, its presence and stability under lowermost-mantle conditions remain uncertain. Here we report high-pressure electrical conductivity measurements of Fe2+- and Fe3+-bearing pyroxene glasses (Fe3+/ΣFe ≈ 0.5), used as analogs of silicate melts, up to megabar pressures at room temperature. At lower pressures, conductivity increases with pressure and iron content, consistent with electron-hole hopping between Fe2+ and Fe3+. Above 77–85 GPa, all samples show a marked conductivity decrease, suggesting a pressure-induced spin transition of Fe3+. Previous studies have suggested that lower-mantle silicate melts may be enriched in Fe3+, and iron spin-state changes may modify iron partitioning between silicate melts and coexisting crystalline phases. Therefore, the Fe3+ spin transition inferred here may affect the evolution of deep-mantle melts through pressure-dependent changes in iron partitioning behavior. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 2026 Clinical utility of diagnosing Lynch syndrome in gynecologic oncology: a joint statement from four Japanese academic societies EN Shinya Sato Department of Obstetrics and Gynecology, Faculty of Medicine, Tottori University Kenta Masuda Department of Obstetrics and Gynecology, Keio University School of Medicine Katsutoshi Oda Division of Integrative Genomics, Graduate School of Medicine, The University of Tokyo Takeshi Kuwata Department of Genetic Medicine and Services, National Cancer Center Hospital East Takeshi Nakajima Division of Hereditary Tumors, Department of Genetic Oncology, Osaka International Cancer Institute Masayoshi Yamada Endoscopy Division, National Cancer Center Hospital Tatsuro Yamaguchi Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Akira Hirasawa Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaki Mandai Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine Kohji Tanakaya Department of Surgery, National Hospital Organization Iwakuni Medical Center Hideyuki Ishida Department of Clinical Genetics, Saitama Medical Center, Saitama Medical University Takayuki Yoshino Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East Aikou Okamoto Department of Obstetrics and Gynecology, Sanno Hospital, International University of Health and Welfare Lynch syndrome (LS) is an autosomal dominant cancer predisposition syndrome, associated with substantially increased risks of colorectal and gynecologic malignancies. Endometrial cancer may serve as a sentinel cancer for LS, placing gynecologists and gynecologic oncologists in a key position for early recognition and long-term management. This joint statement was developed through a multidisciplinary process involving the Japan Society of Gynecologic Oncology, the Japan Society of Clinical Oncology, the Japanese Society of Hereditary Tumors, and the Japanese Society for Cancer of the Colon and Rectum. It aims to clarify the clinical utility of diagnosing LS in gynecologic oncology within the Japanese healthcare system. We outline a tumor-first paradigm in which universal mismatch repair immunohistochemistry and/or microsatellite instability testing for endometrial cancer facilitates LS detection and provides actionable biomarkers for systemic therapy. This statement summarizes the clinical impact of LS diagnosis across gynecologic oncology. We highlight patterns of synchronous and metachronous malignancies and the prevalence of LS in ovarian cancer, particularly in endometrioid and clear–cell subtypes. We discuss surgical implications, including risk-reducing hysterectomy with bilateral salpingo-oophorectomy, consideration of concomitant gynecologic risk-reducing surgery during colorectal cancer resection, and individualized ovarian preservation in selected early-stage endometrial cancer or atypical endometrial hyperplasia. We also review the treatment relevance of deficient mismatch repair/microsatellite instability-high status for immune checkpoint inhibitors and emerging fertility-preserving approaches, and address surveillance, cascade testing for relatives, implementation barriers, and the need for multidisciplinary pathways and healthcare system–level support to ensure equitable access to genetic counseling and testing. No potential conflict of interest relevant to this article was reported.

Public Library of Science (PLoS) Acta Medica Okayama 1932-6203 21 8 2026 Study protocol: Effect of inulin supplementation on gut microbiota in patients with oral lichen planus ― A double-blind, randomised, placebo-controlled parallel-group trial e0356180 EN Koki Nambu Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Naoki Kaneko Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Shiho Yokomizo Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Hu Chen Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Lijing Yan Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Wang Shiyao Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Ryusei Shizuma Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Eiji Iwata Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yukiko Ohyama Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Shohei Akagawa Department of Pediatrics, Kansai Medical University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shintaro Kawano Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Masafumi Moriyama Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Oral lichen planus is a chronic inflammatory disease of the oral mucosa characterised by immune dysregulation, but its pathogenesis remains incompletely understood and no curative treatment has been established. Our previous work showed that patients with oral lichen planus exhibit gut dysbiosis, including reduced microbial diversity and depletion of butyrate-producing bacteria. Because butyrate promotes regulatory T-cell differentiation and supports immune homeostasis, targeting this dysbiosis may represent a microbiota-directed approach for immune modulation in oral lichen planus. This study aims to investigate the effects of inulin supplementation on the gut microbiota and related immune markers in patients with oral lichen planus. This multicentre, double-blind, randomised, placebo-controlled parallel-group trial will enrol 80 patients with oral lichen planus. Participants will be randomly assigned in a 1:1 ratio to receive either inulin (8 g/day) or a maltose placebo for 4 weeks, in addition to standard care. The primary outcome is the change in the relative abundance of prespecified butyrate-producing gut bacteria from baseline to the end of intervention at Week 6. Secondary outcomes include changes in gut microbiota diversity, salivary microbiota composition, faecal short-chain fatty acid concentrations, peripheral blood regulatory T-cell counts, blood test parameters, and clinical symptoms of oral lichen planus. Analyses will follow the intention-to-treat principle, and between-group differences will be assessed using appropriate statistical methods. This trial is designed to evaluate, in a randomised placebo-controlled setting, whether a microbiota-directed intervention can modify gut microbial profiles and related immune markers in patients with oral lichen planus. The findings are expected to clarify whether inulin supplementation can modify gut microbial profiles and related immunological markers in patients with oral lichen planus. Trial registration: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000060840, registered on 1 April 2026 (https://rctportal.mhlw.go.jp/detail/um?trial_id=UMIN000060840#). No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0449-3060 67 4 2026 Enhancement of antioxidant function in various organs in mice using combined thermal and radon inhalation treatment 538 549 EN Shogo Miyanaga Graduate School of Health Sciences, Okayama University Ayumi Tanaka Graduate School of Health Sciences, Okayama University Reiju Takenaka Graduate School of Health Sciences, Okayama University Shota Naoe Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Shuna Goto Graduate School of Health Sciences, Okayama University Mitsuki Nagano Graduate School of Health Sciences, Okayama University Kotaro Tano Graduate School of Health Sciences, Okayama University Norie Kanzaki Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Akihiro Sakoda Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Takahiro Kataoka Faculty of Health Sciences, Okayama University Enhancing antioxidant function is a key strategy for preventing and treating oxidative stress-related diseases. Radon inhalation and thermal treatment (TT) increase the levels of antioxidant enzymes, such as superoxide dismutase (SOD). The positive effects of this combination on pain-related diseases have been reported; however, few studies have elucidated the underlying mechanisms. In this study, we examined the enhancement of antioxidant function in various organs of mice subjected to combined TT and radon inhalation. The mice were placed in an incubator once daily for 40 min at 38.5 ± 0.5°C and treated for 1, 3 and 7 days. The mice then inhaled radon at a concentration of 2000 Bq/m3 for 24 h. The characteristic changes in antioxidant function following combined TT and radon inhalation could be categorized into four groups: (i) increased antioxidant function in the brain and colon; (ii) increased or decreased antioxidant function, as observed in the kidney; (iii) decreased antioxidant function, such as in the lungs and (iv) no changes, such as in the small intestine, spleen, pancreas, heart, liver and stomach. Additionally, SOD may be the antioxidant enzyme most sensitive to combined TT and radon treatment. Collectively, the combined treatment may be the most effective in activating antioxidative functions in the brain and colon. This study provides new insights into the effects of combined TT and radon inhalation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 1 2025 Association Between Dinner-to-Bed Time and Gastroesophageal Reflux-Related Diseases in Children e77709 EN Kensuke Uraguchi Department of Epidemiology, 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 Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Soshi Takao Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Seiichiro Makihara Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mizuo Ando Department of Otolaryngology- Head and Neck Surgery, 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 Introduction: Gastroesophageal reflux disease (GERD) is characterized by esophageal mucosal injury due to the reflux of gastroduodenal contents. Typical symptoms include heartburn and acid regurgitation. In addition, gastroesophageal reflux (GER) can influence conditions such as otitis media, rhinitis, and asthma. This study aimed to examine the association between dinner-to-bed time and GER-related diseases, such as otitis media, allergic rhinitis, and asthma.<br> Methods: This was a longitudinal cohort study using secondary data. Data were collected from a large-scale birth cohort study conducted in Japan including babies born in 2001 and 2010. Dinner-to-bed time was categorized as “longer dinner-to-bed time" (>120 minutes), “shorter dinner-to-bed time" (≤120 minutes or less), and “irregular dinner-to-bed time.” Modified Poisson regression with robust variance was used to estimate risk ratios (RRs).<br> Results: A total of 60,392 children were included in this study. Children with shorter dinner-to-bed time had a higher risk of asthma (adjusted RR (aRR) = 1.10; 95% confidence interval (CI), 1.03-1.18) than those with longer dinner-to-bed time. However, no significant association was observed between shorter dinner-to-bed time and otitis media or allergic rhinitis. Furthermore, supplementary analyses revealed that the risk of asthma was significantly higher in children born in 2001 (aRR = 1.13; 95% CI, 1.04-1.22).<br> Conclusion: This study showed that dinner-to-bed time within 120 minutes after dinner increases the risk of developing asthma. This underscores the importance of considering lifestyle modifications, as certain pediatric asthma cases may be influenced by behaviors that promote GER. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1523-7060 2026 Cathodic AziridinationUsing Dichloramine-Tas a Nitrogen Source EN Eisuke Sato Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kanon Nagamine Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koichi Mitsudo Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Seiji Suga Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Aziridines are valuable motifs in organic synthesis due to their biological activities and their utility as synthetic intermediates. Although electrochemical methods have been developed for aziridine synthesis, these approaches rely on anodic oxidation. This study reports the first cathodic reduction-promoted aziridine formation using dichloramine-T as a nitrogen source. The reaction conditions were optimized via Gaussian process regression. Overall, this strategy enables aziridine formation with broad substrate scope, providing a practical platform that expands the electrochemical synthesis toolbox. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1936-0568 20 1 2026 Early-Stage Oral Squamous Cell Carcinoma in Adolescents and Young Adults Compared with Older Patients Exhibits Distinct Clinicopathological Features 88 EN Sawako Ono Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsutoshi Hirose Department of Oral and Maxillofacial Pathology, Osaka University Graduate School of Dentistry Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsuya Abe Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University Shintaro Sukegawa Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine Masanori Masui Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chihoko Ikeda Department of Oral Pathology, Osaka Dental University Madoka Isomura Department of Diagnostic Pathology, School of Medicine, Fujita Health University Yuri Tachibana Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Faculty of Medicine Junya Ono Department of Pathology, The Nippon Dental University School of Life Dentistry at Niigata Katsumitsu Shimada Department of Clinical Pathophysiology, School of Dentistry, Matsumoto Dental University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidetaka Yamamoto Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose This study aimed to compare the clinicopathological features of stage I–II oral squamous cell carcinoma (OSCC) between adolescents and young adults (AYAs) and older patients, and to identify prognostic factors in AYA OSCC.<br> Methods Forty-eight AYA patients aged 15–39 years and 69 older patients aged ≥ 65 years with surgically treated stage I–II OSCC were retrospectively analyzed. Histological evaluation, survival analysis, immunohistochemistry for p53, p16, and MTAP, high-risk HPV RNA in situ hybridization, and fluorescence in situ hybridization for CDKN2A and MTAP were performed.<br> Results Compared with older patients, OSCCs in AYAs were more frequently located on the tongue (93.7% vs. 47.8%) and more often exhibited a superficial spreading growth pattern (60.4% vs. 31.8%). AYA tumors more frequently showed modified WPOI-1, high tumor budding, and abnormal p53 immunophenotypes (85.4% vs. 68.1%). AYA patients showed significantly better overall and disease-free survival than older patients. Within the AYA group, depth of invasion (DOI) > 5 mm was associated with distant metastasis and poorer overall and disease-free survival. Postoperative lymph node metastasis occurred in 31.2% of AYAs. Univariable analysis suggested that clinical stage II, tumor thickness > 5 mm, DOI > 5 mm, and tumor budding scores 1–2 were associated with postoperative lymph node metastasis. Molecular status, including p53, p16/CDKN2A, and MTAP, did not provide robust prognostic stratification.<br> Conclusion Early-stage AYA OSCC exhibits distinct clinicopathological features. DOI was the strongest prognostic indicator, whereas clinical stage, tumor thickness, and tumor budding may provide additional prognostic information regarding the risk of late nodal metastasis. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0032-0781 66 12 2025 ABA receptor isoforms differently regulate stomatal movements and generation of reactive oxygen species in ABA signaling in Arabidopsis guard cells 1811 1822 EN Ye Yin Graduate School of Environmental and Life Science, Okayama University Yuki Hayashi Graduate School of Science, Nagoya University Monira Sirajam Graduate School of Environmental and Life Science, Okayama University Oumayma Shaiek Graduate School of Environmental and Life Science, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Toshinori Kinoshita Graduate School of Science, Nagoya University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Izumi C Mori Institute of Plant Science and Resources, Okayama University ABA signaling in stomatal guard cells is crucial for plants to cope with abiotic stress condition. Pyrabactin is a synthetic agonist of ABA that has a selective affinity to limited isoforms of ABA receptors. Here, we investigated the differential utilization of downstream signaling events in guard cell ABA signaling under specific receptor isoforms taking advantage of pyrabactin affinity. Pyrabactin-induced stomatal closure as well as ABA, while it did not inhibit stomatal opening. Plasma membrane inwardly rectifying K+ channel was not regulated by pyrabactin, while H+-ATPase activation was negatively regulated by pyrabactin. Pharmacological and molecular genetic evidence supported that reactive oxygen species production occurred differentially between the closure-inducing and opening-inhibiting signals in guard cells. These findings offer a previously unidentified mechanism for ABA signaling events promoting closure induction and opening inhibition of stomata, which were distinct from each other and governed by different ABA receptor isoforms discriminable by their affinity for pyrabactin. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1526-9914 27 7 2026 Potential of quantitative X‐ray imaging from photon‐counting CT: A novel analysis based on effective atomic number and physical density e70673 EN Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Mana Mitani Division of Radiological Technology, Medical Support Department, Okayama University Hospital Yusuke Morimitsu Division of Radiological Technology, Medical Support Department, Okayama University Hospital Noriaki Akagi Division of Radiological Technology, Medical Support Department, Okayama University Hospital Fumiyo Higaki Department of Radiology, 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 Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation Kanazawa University Kanazawa Ishikawa Japan Background: Conventional CT assessment of lung lesions is based mainly on morphological features. CT values represent relative X-ray attenuation that does not directly reflect tissue composition and/or physical density. Quantitative imaging using photon-counting CT (PC-CT) has the potential to provide quantitative parameters, such as effective atomic number (Zeff) and effective physical density (ρeff).<br> Purpose: The purpose is to develop and demonstrate the potential of an algorithm that generates both the Zeff and ρeff images, derived directly from virtual monoenergetic images (VMIs) acquired with a clinical PC-CT system.<br> Methods: The ρeff image was generated by fitting a database of mass attenuation coefficients (μ/ρ) to the measured linear attenuation coefficients (μ), which were obtained from two VMIs at 70 and 100 keV. As an effective material, Zeff information was also determined and fed back into the ρeff calculation. An in-house low-density phantom was scanned for quantitative evaluation of ρeff. In addition, to demonstrate the applicability of our procedure to actual clinical imaging, representative chest PC-CT images from patients were analyzed.<br> Results: In experiments using low-density phantoms, the CT values did not necessarily correlate with Zeff values, but they showed a very good correlation with the ρeff values. The ρeff values calculated using our procedure correlated well with the correct values of ρ. A relative root mean square error of ρeff calculation was 5.5%. Furthermore, we found that in pulmonary diagnosis, image contrast information from ρeff makes it easier to identify and distinguish lesions compared to that from Zeff.<br> Conclusions: The proposed procedure directly generated Zeff and ρeff images from PC-CT data and enabled quantitative interpretation of CT value in terms of elemental composition and physical density. In this study, the feasibility of generating Zeff and ρeff images was demonstrated. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0021-9258 302 8 2026 Proton pump rhodopsins for optogenetic manipulation of biological activities and beyond 113318 EN Keiichi Kojima Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miyu Inokuchi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Sudo Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Water (H2O), the principal component of living organisms including humans, dissociates into H+ and OH- in aqueous environments, and the resulting H+ concentration determines both cellular pH and the proton motive force (PMF) across cellular membranes. These physicochemical parameters are fundamental regulators of a wide range of biological processes. Optogenetics enables the manipulation of biological and cellular functions using light, typically through the ectopic expression of microbial rhodopsins as photoreceptive proteins in target cells or organs. This review provides a comprehensive overview of optogenetic studies employing H+ pump rhodopsins in diverse biological systems and highlights their growing relevance to neuroscience, cell biology, bioengineering, and therapeutic research. Notably, optical control of H+ concentration allows the precise modulation of neural and non-neural activities in animals and bacteria, highlighting the broad applicability and significant potential of H+ pump rhodopsins for optogenetics. Based on previous and current studies, we discuss how further expansion of the molecular toolkit of H+ pump rhodopsins could enable increasingly fine-tuned manipulation of intracellular pH dynamics and PMF for probing cellular physiology and designing next-generation therapeutic strategies and consider emerging directions that extend beyond classical optogenetics toward the optical control of bioenergetic and chemical processes. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2367-0932 10 7 2026 Photochemical Oxidative Esterification of Aldehydes with Radical-Sensitive Alcohols via CH Bromination e70221 EN Nova Alfian Hariyanto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haru Ando Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Atsuya Miyamoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyoshi Takamura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Isao Kadota Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kenta Tanaka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Photochemical esterification is an attractive strategy for the synthesis of multifunctionalized esters, and the use of aldehydes as substrates offers an alternative to conventional carboxylic acid–based approaches. In particular, reactions via acyl halide intermediates are useful for accessing functionalized esters; however, examples of such transformations remain limited so far, and their compatibility with radical-sensitive alcohols remains relatively unexplored. Here, we report a photochemical oxidative esterification of aldehydes with radical-sensitive alcohols enabled by CH bromination. This reaction proceeds without stoichiometric additives, such as bases, and enables the incorporation of a broad range of radical-sensitive functional groups into esters. Thus, it represents a promising platform for the synthesis of pharmaceuticals and functional materials. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0024-6093 58 8 2026 On Nielsen equivalence classes of two‐element generators of mapping class groups e70454 EN Susumu Hirose Department of Mathematics, Faculty of Science and Technology, Tokyo University of Science Naoyuki Monden Department of Mathematics, Faculty of Science, Okayama University We show that there are infinitely many Nielsen equivalence classes of the mapping class group of a closed oriented surface of genus at least eight. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0947-6539 2026 Synthesis of Tris(indol-3-yl)methanes From Indoles, CO2, and Dimethylphenylsilane With BPh3: Two-Step Construction of π-Conjugated Systems e71464 EN Sha Li Graduate School of Environmental, Life, Natural Science and Technology, Okayama University So Saibara Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Reito Yasui Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuto Takaishi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Natsumi Nitta Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tadashi Ema Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tris(indol-3-yl)methanes were synthesized from indoles, CO2, and PhMe2SiH in the presence of BPh3 in acetonitrile at 50°C. This is the first CO2 fixation reaction forming the aliphatic methine (>CH─) group. The isotope-labeling experiments clearly demonstrated that the carbon and hydrogen atoms of the methine group originated from carbon dioxide and dimethylphenylsilane, respectively. The mechanism for the multicomponent cascade reaction was elucidated by DFT calculations. One of the CO2-derived products, tris(4-bromo-1-methylindol-3-yl)methane, underwent palladium-catalyzed intramolecular cascade reactions for the selective formation of two novel polycyclic heteroaromatic compounds, where the methine C(sp3) atom originating from CO2 was converted into aromatic C(sp2) atoms. One is formally produced via double direct C─H arylation, Wacker-type oxidation, dehydrogenation, and debromination, while the other seems to be produced via the intramolecular homocoupling of aryl bromide, direct C─H arylation, Wacker-type oxidation, and dehydrogenation. Both of them are new intramolecular cascade reactions that are useful for the short-step construction of nitrogen-doped nanographenes. On the other hand, one of the CO2-derived products, tris(1-pentylindol-3-yl)methane, was converted into tris(1-pentylindol-3-yl)methylium methanesulfonate, which is a potential antitumor drug. This is the first derivatization of CO2 to a cationic C(sp2) center. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0305-1846 52 4 2026 Frontotemporal Lobar Degeneration‐TDP Type C With Striatal Glial Cytoplasmic Inclusions and Motor Neuron Degeneration e70090 EN Akiko Uchino Department of Neuropathology (Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Kazutomi Kanemaru Department of Neurology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Airi Tarutani Department of Clinical Medical Sciences, Tokyo Metropolitan Institute of Medical Science Masato Hasegawa Department of Clinical Medical Sciences, Tokyo Metropolitan Institute of Medical Science Hiroya Naruse Department of Neurology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shigeo Murayama Department of Neuropathology (Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Yuko Saito Department of Neuropathology (Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0168-0102 229 2026 Enhanced calcium activity and transcriptomic alterations in iPSC-derived neurons from BAFME patients with repeat expansions 105080 EN Yuki Nagasako Department of Neurology, Graduate School of Medicine, The University of Tokyo Mitsuru Ishikawa Department of Physiology, Keio University School of Medicine Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sopak Supakul Department of Physiology, Keio University School of Medicine Sumihiro Maeda Department of Physiology, Keio University School of Medicine Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Shoji Tsuji Department of Neurology, Graduate School of Medicine, The University of Tokyo Hideyuki Okano Department of Physiology, Keio University School of Medicine Benign adult familial myoclonus epilepsy (BAFME) is caused by intronic TTTCA and TTTTA repeat expansions in SAMD12 and other genes; the neuronal basis of cortical hyperexcitability, however, remains unclear. We generated induced pluripotent stem cell (iPSC)-derived glutamatergic and GABAergic neurons from three BAFME1 patients and examined functional and transcriptomic phenotypes. Patient-derived neurons retained the pathogenic repeat expansions and showed a tendency toward upstream intronic RNA accumulation. Calcium imaging revealed increased spontaneous Ca2 + transient frequency in both neuronal subtypes, indicating heightened activity. Pharmacological profiling demonstrated attenuated responses to calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor (CP-AMPAR) blockade and GABAA receptor antagonism in GABAergic neurons, suggesting altered inhibitory signaling. RNA sequencing revealed transcriptomic alterations without differential expression of ion channels and neurotransmitter receptors. In glutamatergic neurons, ATF4-regulated genes, including SLC7A5 encoding LAT1, a Kv1.2 channel modulator, were downregulated. Reduced SLC7A5 expression was validated at both mRNA and protein levels. In GABAergic neurons, synapse-associated genes PTPRD and GPC6 were upregulated. TCERG1L and NLRP2 were suppressed across both neuronal subtypes. These findings suggest subtype-specific alterations may contribute to neuronal hyperexcitability in BAFME and provide a platform for mechanistic studies of repeat expansion-associated epilepsies. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-2607 14 7 2026 Upregulation of the Outer Membrane Protein OmpV and Its Role in Polymyxin B Stress Adaptation in Vibrio mimicus 1527 EN Shin-ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuta Onodera Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunki Annoi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Basilua Andre Muzembo Research Center for Intestinal Health Science, Okayama University Daisuke Imamura Research Institute of Nursing Care for People and Community, University of Hyogo OmpV is an outer membrane protein found in a variety of Gram-negative bacteria. In this study, we demonstrated that V. mimicus strain CS-66, isolated from a patient with diarrhea, was resistant to polymyxin B (PL-B) and colistin (CL) but susceptible to chloramphenicol and ciprofloxacin. When strain CS-66 was cultured in Luria–Bertani broth containing a sub-minimal inhibitory concentration of each antibiotic used for the susceptibility tests, ompV expression as assayed by reverse transcription-qPCR, significantly increased regardless of the antibiotic tested. In contrast, cell aggregation during the early log phase was observed only when the strain was grown in the broth supplemented with PL-B or CL. A space-filling model of V. mimicus OmpV was generated. The model showed that, although OmpV adopted a β-barrel conformation, it had closed top and bottom ends and possessed a lateral cavity. Structural analysis further indicated that the interior of this lateral cavity was negatively charged and sufficiently large to accommodate PL-B. These results suggest that V. mimicus may adapt to PL-B stress through physical sequestration within the negatively charged cavity of OmpV. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0022-1759 541 2025 Development of a novel histidine-rich glycoprotein measurement system as a biomarker for sepsis 113868 EN Takaoki Uchiumi Diagnostic Drug Office, Shionogi & Co., Ltd. Masahiro Nishibori Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoko Inoue Diagnostic Drug Office, Shionogi & Co., Ltd. Hiroshi Nishi Diagnostic Drug Office, Shionogi & Co., Ltd. Norio Ota Diagnostic Drug Office, Shionogi & Co., Ltd. The plasma histidine-rich glycoprotein concentration is a marker of sepsis severity. In this study, we generated selective and specific monoclonal antibodies against histidine-rich glycoprotein for use in a prototype enzyme-linked immunosorbent assay-based in vitro diagnostic system. First, we investigated the properties of monoclonal antibodies produced by 21 hybridomas that we developed using immunized mice, and we identified monoclonal antibodies 69-1A and 75-2D to be the most suitable combination for use in the sandwich enzyme-linked immunosorbent assay. Wild-type histidine-rich glycoprotein (Form-1, 75 kDa) with a proline residue at amino acid position 204 is the most common isoform of the protein in humans, followed by its variant (Form-2, 77 kDa), which has a serine residue at position 204.<br> The epitope mapping was examined for the HRG amino acid sequence with 69-1A and 75-2D mAbs to achieve the identification of respective specific binding domains, though the other kinds of mAbs showed considerably complex domains. The identified epitopes recognized by 69-1A and 75-2D monoclonal antibodies did not span position 204. Furthermore, immunoprecipitation-immunoblotting analysis showed that the 69-1A and 75-2D monoclonal antibodies could bind to both Form-1 and Form-2 in human plasma samples. Thus, these two new antibodies can be used to clearly detect both forms of histidine-rich glycoproteins in human plasma samples. In our analysis of clinical samples by enzyme-linked immunosorbent assays using various combinations of our newly synthesized antibodies, we found that the histidine-rich glycoprotein concentration was significantly lower in plasma samples from septic patients than in those from healthy volunteers (p < 0.01). Thus, our novel analysis system using the new antibodies is expected to be a useful tool for sepsis research, and it may be adapted as an in vitro diagnostic tool for many other kinds of diseases in the future. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1746-8094 127 2026 Outcome-aware and interpretable subtyping of chronic kidney disease: an analysis of the FROM-J study 111090 EN Tianyi Shi Department of Computer Science, University of Tsukuba Xiucai Ye Department of Computer Science, University of Tsukuba Wenyu Xi Department of Computer Science, University of Tsukuba Akira Imakura Department of Computer Science, University of Tsukuba Kaori Mase Department of Nephrology, Faculty of Medicine, University of Tsukuba Ryoya Tsunoda Department of Nephrology, Faculty of Medicine, University of Tsukuba Chie Saito Department of Nephrology, Faculty of Medicine, University of Tsukuba Akihiko Kato Blood Purification Unit, Hamamatsu University School of Medicine Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoichi Maruyama Department of Nephrology, Nagoya University Graduate School of Medicine Takashi Wada Department of Nephrology and Rheumatology, Kanazawa University Ichiei Narita Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences Kunihiro Yamagata Department of Nephrology, Faculty of Medicine, University of Tsukuba Tetsuya Sakurai Department of Computer Science, University of Tsukuba Chronic kidney disease (CKD) affects approximately 10% of the global population and exhibits substantial heterogeneity in disease progression and clinical outcomes. Despite ongoing efforts to develop new therapeutic strategies, the number of patients progressing to end-stage kidney disease (ESKD) and the incidence of cardiovascular disease (CVD) continue to rise. Although severity classification systems for CKD are well established and refined, they remain insufficient to capture prognostically relevant patient subtypes. In this study, we developed an outcome-aware and interpretable clustering framework for CKD subtyping using data from the FROM-J cohort with prognostic follow-up. A supervised XGBoost model was first trained to predict a ≥ 30% decline in estimated glomerular filtration rate (eGFR), a surrogate marker of CKD progression. SHAP (SHapley Additive exPlanations) values derived from this model were then used to quantify outcome-relevant feature contributions. Based on these feature attributions, a similarity graph was constructed, and spectral clustering was performed to identify patient subtypes driven by prognostic relevance. The proposed framework identified four CKD subtypes with distinct baseline clinical characteristics and significantly different risks of renal replacement therapy (RRT) and cardiovascular disease (CVD) events. Serum albumin, blood urea nitrogen (BUN), and smoking status consistently emerged as key features defining subtype structure and prognosis. Robust risk stratification was preserved even when clustering was restricted to these three routinely measured variables. Overall, our findings demonstrate that integrating outcome-driven feature attribution into clustering enables interpretable and clinically relevant CKD subtyping, providing a practical approach for characterizing disease heterogeneity and supporting risk stratification and personalized management. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 2165-0497 2026 Escalation of CTX-M-producing extensively drug-resistant Shigella spp. in Kolkata, India, following the COVID-19 pandemic e02824-25 EN Puja Bose Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Gourab Halder Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Pratanu Kayet Division of Bioinformatics, ICMR-National Institute for Research in Bacterial Infections Goutam Chowdhury Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Surajit Basak Division of Bioinformatics, ICMR-National Institute for Research in Bacterial Infections Deboleena Roy Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Daisuke Imamura Research Center for Intestinal Health Science, Okayama University Shin-ichi Miyoshi Research Center for Intestinal Health Science, Okayama University Masatomo Morita Department of Bacteriology I, National Institute of Infectious Diseases Thandavarayan Ramamurthy Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Hemanta Koley Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Santasabuj Das Division of Clinical Medicine, ICMR-National Institute for Research in Bacterial Infections Asish Kumar Mukhopadhyay Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections Shigella spp. is recognized by the World Health Organization as a high-priority pathogen due to its global prevalence, unique pathogenic mechanisms, and growing antimicrobial resistance (AMR). Nearly half of all Shigella strains worldwide are now multidrug-resistant (MDR), and the emergence of extensively drug-resistant (XDR) variants―resistant to ciprofloxacin, ceftriaxone, and azithromycin―has severely limited effective treatment options. The present study is based on prospective laboratory surveillance involving 323 Shigella isolates collected during 2021–2023, with pre-COVID-19 pandemic data included from a previously published study solely for historical comparison. The presence of antibiotic resistance genes (ARGs) was investigated, and whole-genome sequencing (WGS) was performed on representative isolates to assess phylogenetic relatedness with global isolates. Approximately 10% of isolates exhibited resistance to third-generation cephalosporins. While only 3% of Shigella isolates carried the blaCTX-M-15 gene from 2013 to 2019, its prevalence increased to 26% by 2022–2023. Among 38 ceftriaxone-resistant S. sonnei isolates, 33 were also resistant to azithromycin, categorizing them as XDR. These isolates showed 48% clonal similarity and high phylogenetic resemblance to the isolates reported from England. Hybrid genome assembly revealed a plasmid harboring both the blaCTX-M-15 and mphA ARGs. Conjugation experiments and plasmid profiling confirmed the plasmid’s transferability. We report a rising trend in third-generation cephalosporin resistance among Shigella spp., primarily driven by the spread of extended-spectrum β-lactamase-producing S. flexneri and the emergence of XDR S. sonnei. These findings underscore the urgent need for strengthened national AMR containment strategies and enhanced international surveillance of cephalosporin-resistant Shigella to mitigate this growing public health threat. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0024-4937 542-543 2026 Serpentinization parageneses controlled by lithological variations among olivine gabbro and peridotite from the Atlantis Massif, Mid-Atlantic Ridge 108716 EN Toshio Nozaka Department of Earth Sciences, Okayama University Shun Kazumata Department of Earth Sciences, Okayama University Frieder Klein Department of Marine Chemistry and Geochemistry, Woods Hole Oceanographic Institution Serpentinization of olivine impacts the geochemical and ecological environment via molecular hydrogen production, promoted by iron oxidation to form magnetite and ferric iron in serpentine. Previous studies suggested that serpentinization proceeds with various reactions and the extent of iron oxidation is variable depending on the reaction pathways. To examine the effect of lithological variation on reactions at an incipient stage of serpentinization, we carried out microscopic observations, electron-probe analyses, and Raman spectroscopy of serpentine veins cutting olivine in gabbroic rocks and peridotites from the Atlantis Massif, Mid-Atlantic Ridge. The results indicate that the serpentine veins in the proximity of olivine dominantly comprise lizardite mixed with variable minor phases or components depending on igneous lithology: brucite in peridotites, troctolites, and primitive olivine gabbros; cronstedtite-bearing serpentine, commonly without brucite, in some troctolites and slightly evolved olivine gabbros; and neither brucite nor cronstedtite component in evolved olivine gabbros. This suggests that incipient-stage serpentinization paragenesis is dominantly controlled by silica activity reflecting lithological variation. In addition to magnetite, the formation of cronstedtite in gabbroic rocks has the potential to produce hydrogen. The presence or absence of brucite and cronstedtite could affect the timing and magnitude of iron oxidation and hydrogen production during serpentinization. Considering the predominance of gabbroic rocks in the lower oceanic crust, the variation in incipient-stage serpentinization paragenesis in gabbroic rocks may have an impact on the redox state and ecological environment around the (sub)seafloor. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 2296-4185 14 2026 High horizontal force and lateral force transmission induced by the twist of the Achilles tendon 1874501 EN Shota Enomoto Graduate School of Education, Okayama University Kohta Ito Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology (AIST) The Achilles tendon―the largest and strongest of the many tendons in the human body―consists of subtendons arising from each head of the triceps surae. These subtendons run helically and intertwine to form a twisted three-dimensional structure. More than a century has passed since the twisted structure of the Achilles tendon was first described, and numerous studies have investigated its functional morphology. However, it remains unclear how the presence or degree of twist affects the mechanical function of the lower limbs. Here, using finite element models of the Achilles tendon with and without twist, we show that the presence and degree of twist can modulate the forces transmitted from muscle to skeleton in a complex manner. In contrast to the model without twist, the twisted models clearly exhibit anterolaterally directed horizontal forces at the distal end under a simple proximal tensile load. The lateral and anterior components reach approximately 101 N and 63 N, respectively. Furthermore, the twisted structure induces inter-subtendon force transmission, and the magnitude of the transmitted force increases with increasing degree of twist. These results indicate that the uniaxial contractile force generated by the triceps surae is transformed into triaxial forces by the twisted Achilles tendon and is redistributed in a complex three-dimensional manner through inter-subtendon interactions. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1463-9262 28 29 2026 Terpolymerization of epoxide, oxetane, and CO2 for the synthesis of polycarbonates with high CO2 contents, physical tunability, and enzymatic degradability 12214 12224 EN Kaito Niki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Chihiro Maeda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tadashi Ema Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Although poly(cyclohexene carbonate) (PCHC) synthesized by the copolymerization of cyclohexene oxide (CHO) and CO2 is a promising material, the physical properties of this material need to be altered and tuned for its wider applications. To this end, we employed a terpolymerization strategy increasing the CO2 content in the resulting polymers. Terpolymerization of CHO, oxetane, and CO2 using AlIII porphyrin catalysts with quaternary ammonium halides afforded polycarbonates with high CO2 contents, physical tunability, and enzymatic degradability. The counter anions of the catalysts were crucial factors in the formation of the poly(trimethylene carbonate) (PTMC) unit. 1a with bromide ions preferentially produced trimethylene carbonate (TMC) over PTMC, while 1d with chloride ions suppressed the formation of TMC and produced PCHC–PTMC directly. PCHC–PTMC showed glass transition temperatures (Tg) between 69 °C and −9 °C, depending on the PCHC/PTMC ratio. The tensile test revealed that the PTMC unit contributed to the softening of the film materials. For example, a film material with a CO2 content of 38 wt% showed 505% elongation at break with an elastic character, which contrasted starkly with the 1.3% elongation at break of PCHC with a CO2 content of 31 wt%. Moreover, the selective degradation of the PTMC unit in PCHC–PTMC was achieved with lipases, and a gradient character in the sequence structure was suggested. Overall, PCHC–PTMC is an environmentally benign and sustainable CO2-based polycarbonate. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1344-6223 84 2026 Factors that delay discovery in cases of death at home in Japan 102895 EN Yukie Yamasaki Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nanako Tamiya Department of Health Services Research, Faculty of Medicine, University of Tsukuba Hideki Yamamoto Department of Environmental Health, Faculty of Pharma-Science, Teikyo University Masanobu Miura Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaori Taniguchi Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chie Kobayashi Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Motomura Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ayako Himemiya-Hakucho Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Miyaishi Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences In Japan, solitary deaths have become a social issue, with an increasing number of cases in which the body is discovered long after death. This study aimed to clarify the factors underlying such delays. Cases of death at home were extracted from forensic autopsies. In each case, we collected information about the deceased and their living conditions. The postmortem interval until finding (PMI-f) was calculated by measuring the time between death and discovery. We classified the cases into long PMI-f (LPMI-f; having PMI-f of ≥3 days) and short PMI-f (SPMI-f; having PMI-f of <3 days), and examined the factors that lead to LPMI-f. The characteristics of the group living alone with a PMI-f of <24 h and living with family or acquaintances with an LPMI-f were also analyzed. Among the 420 cases included, 244 (58.1%) were in the LPMI-f group. The LPMI-f group had higher number of males; older individuals; those living alone; those found inside their homes; single, retired, or non-employed individuals; those without long-term care certification; and those with drinking habits. Forty-seven individuals lived alone and had PMI-f of <24 h. Regular visits from relatives living separately led to early detection after death. In the LPMI-f group, 56 individuals lived with family or acquaintances. The absence of regular visits can result in delayed discovery after death; however, the time between death and discovery could be shortened by implementing systems such as allowing neighbors to check the person's safety by noticing uncollected mail. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 0094-8276 53 14 2026 Electrical Conductivity of Hydrous Ultramafic Melts With Implications for Origin of Low Velocity Layer Atop of the 410 km Seismic Discontinuity e2026GL122472 EN Takashi Yoshino Institute for Planetary Materials, Okayama University Longjian Xie Center for High Pressure Science & Technology Advanced Research Low-velocity layers (LVLs) above the 410-km discontinuity are commonly attributed to partial melt generated by dehydration melting when hydrous mantle transition-zone material rises into the upper mantle, where water solubility in nominally anhydrous minerals decreases. Interpreting coexisting high-conductivity anomalies requires constraints on the intrinsic conductivity of the melt phase at pressures just above the transition zone. We measured electrical conductivity of hydrous ultramafic melts representative of incipient melts, ranging from 6.3 to 18.6 wt% H2O at 13 GPa using impedance spectroscopy in a Kawai-type multi-anvil apparatus. Hydrous ultramafic melts are extremely conductive, and conductivity increases systematically with H2O content to values comparable to alkali-carbonate melts. The high conductivity implies that even small fractions of interconnected hydrous melt can dominate bulk mantle conductivity. Combining our measurements with geophysical conductance estimates indicates that <1 vol% melt can produce conductive layers thicker than 10 km, consistent with seismological constraints on LVL structure. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0140-7791 2026 Tripartite Interaction Between Penicillium pinophilum-Host Plants and CMV-Y: A Model for Endophyte-Mediated Viral Biocontrol EN Sarah R. Ibiang Group of Plant-Microbe Interactions, Institute of Plant Science and Resources, Okayama University Ivan Galis Group of Plant-Insect Interactions, Institute of Plant Science and Resources, Okayama University Hideki Kondo Group of Plant-Microbe Interactions, Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki Group of Plant-Microbe Interactions, Institute of Plant Science and Resources, Okayama University Plant-fungus-virus tripartite interactions represent complex ecological systems in which mutualistic endophytes can influence host physiology, yet the molecular basis of endophyte-mediated defence remains poorly understood. Here, we demonstrate that the endophytic fungus Penicillium pinophilum EU0013 suppresses the yellow strain of cucumber mosaic virus (CMV-Y) in Solanum lycopersicum and Nicotiana benthamiana. CMV-Y infection induced pronounced oxidative and hormonal perturbations, which were mitigated by P. pinophilum colonisation. Endophyte-associated plants exhibited early accumulation of jasmonate intermediates, consistent with the activation of jasmonate signalling. This response promoted the degradation of jasmonate-ZIM-domain proteins and release of core JA-responsive transcription factors. Virus-induced gene silencing identified MYC2 as a key regulator required for endophyte-mediated antiviral protection, with WRKY17 contributing to defence modulation. In parallel, transcriptome analysis revealed the upregulation of a Dicer-like gene, indicating enhanced engagement of RNA silencing, a primary antiviral mechanism targeting viral RNA. This coordinated activation occurred alongside significant induction of pathogenesis-related proteins, particularly PR9, and improved control of reactive oxygen species. Salicylic acid-responsive defences showed a host-modulated pattern, with PR1 induced by CMV and PR2/PR5 preferentially enhanced in endophyte-associated plants. Collectively, these findings demonstrate that P. pinophilum enhances antiviral immunity through coordinated defence integration pathways, providing a framework for endophyte-based viral disease management. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1639-4488 2026 Triple Oxygen Isotope Compositions of Isotopic Reference Waters: Implications for VSMOW-Scale and VSMOW–SLAP-Scale Δ′17O Calibration EN Ryoji Tanaka The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Andreas Pack Georg-August-Universität Göttingen, Geowissenschaftliches Zentrum Tyler B. Coplen US Geological Survey Triple oxygen isotope ratios of waters are commonly reported on the VSMOW–SLAP scale, whereas comparison with theoretical calculations and assessment of instrumental scale distortion require accurate constraints on the measured isotopic compositions of the primary isotopic reference materials (iRMs) themselves. In particular, the measured δ17OVSMOW and Δ′17OVSMOW values for SLAP and its substitute, SLAP2, remain insufficiently constrained and reported values differ among laboratories. Here, we measured triple oxygen isotope ratios for two primary iRMs (VSMOW and SLAP) and twelve secondary iRMs (VSMOW2, SLAP2, GISP, GRESP, USGS45, USGS46, USGS46a, USGS47, USGS48, USGS49, USGS50 and USGS53) using BrF5 fluorination and dual-inlet isotope-ratio mass spectrometry. For SLAP, we obtained δ18OVSMOW = -55.50 ± 0.15‰ and δ17OVSMOW = -29.66 ± 0.08‰, giving Δ′17OVSMOW = 34 ± 6 per meg (all expanded uncertainties, k = 2). The corresponding values for SLAP2 agree within uncertainty. When expressed on the conventional VSMOW–SLAP scale, our Δ′17OVSMOW–SLAP values for all secondary iRMs with available literature values agree with previously published values within uncertainty, confirming interlaboratory comparability on that scale. In contrast, waters with low δ18O values, Δ′17OVSMOW values are systematically higher than the corresponding Δ′17OVSMOW–SLAP values. These results further suggest that accurate determination of the VSMOW-scale isotopic composition of SLAP and/or SLAP2 across laboratories is essential, particularly for low-δ18O samples, for which the difference between VSMOW-scale and VSMOW–SLAP-scale Δ′17O values becomes large, and for meaningful comparison between measured data and theoretical calculations. No potential conflict of interest relevant to this article was reported.

公益社団法人　日本租税研究協会 Acta Medica Okayama 0288-0768 921 2026 組織再編成の適格要件の再検討−スピンオフの濫用防止を中心として− 166 193 EN No potential conflict of interest relevant to this article was reported.

Ceramic Society of Japan Acta Medica Okayama 1348-6535 134 7 2026 Dielectric response modulation in relaxor (Sr,Ba)Nb2O6 via engineered defect 455 460 EN Ryusei Shiota Graduate School of Natural Science and Technology, Okayama University Takashi Teranishi Graduate School of Natural Science and Technology, Okayama University Shinya Kondo Department of Energy Engineering, Nagoya University Akira Kishimoto Graduate School of Natural Science and Technology, Okayama University Defect engineering provides an effective pathway to tune the dielectric response of relaxor ferroelectrics, yet the roles of individual defect species in tungsten bronze (TTB) systems remain unclear. Here, we investigated how engineered Ti–VO•• defect dipoles and native oxygen vacancies introduced through reduction annealing modify the dielectric properties of relaxor (Sr0.5,Ba0.5)Nb2O6 (0.5-SBN). Ti loading forms stable defect dipoles that generate smaller polar nanoregions (PNRs), suppress their overgrowth, and increase the number of dynamically active PNRs at room temperature, leading to enhanced permittivity ε′ while preserving DC-bias stability and breakdown strength (EB). Reduction annealing generates Nb4+-related local polarizations aligned with the external electric field, which strengthen dipole fluctuations and slightly increase ε′. Electron localization further relaxes the TTB-A2 site disorder–induced random fields, yielding a sharper dielectric peak and promoting more uniform PNR growth. Microwave dielectric spectroscopy combined with electromagnetic simulations revealed that the increases in ε′ for both Ti-loaded and reduced samples (0.5-SBNT and Reduced 0.5-SBN, respectively) originate predominantly from enhanced dipole polarization. Despite grain coarsening in 0.5-SBNT, the EB remained unchanged, indicating that defect dipoles act as pinning centers that inhibit field-induced PNR aggregation. In reduced 0.5-SBN, EB increased up to pO0 = 4.3 × 10−3 atm owing to relaxed random fields, whereas excessive reduction reduced EB through carrier-driven space-charge effects. These results demonstrate that precise control of defect species enables simultaneous optimization of ε′, DC-bias stability, and EB in TTB-type relaxor ferroelectrics. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0941-4355 34 8 2026 Incidence and impact of odontogenic infection-related febrile episodes during perioperative doxorubicin-cyclophosphamide or docetaxel-cyclophosphamide chemotherapy for breast cancer 747 EN Yoshihiko Soga Division of Hospital Dentistry, Okayama University Hospital Kumiko Matsuzaki Division of Hospital Dentistry, Okayama University Hospital Hirotaka Kosaki Division of Hospital Dentistry, Okayama University Hospital Tomoko Kishimoto Division of Hospital Dentistry, Okayama University Hospital Aiko Yoshitomi Division of Hospital Dentistry, Okayama University Hospital Makoto Kajizono Department of Pharmacy, Okayama University Hospital Takashi Makita Department of Pharmacy, Okayama University Hospital Yuta Tanaka Department of Pharmacy, Okayama University Hospital Yoshito Zamami Department of Pharmacy, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyoshi Doihara Department of Surgery, Kawasaki Medical School General Medical Center Background Doxorubicin-cyclophosphamide (AC) and docetaxel-cyclophosphamide (TC) are standard perioperative chemotherapy regimens for breast cancer. Febrile neutropenia (FN) is a common adverse event, and odontogenic infections may contribute to febrile episodes. This study was performed to investigate the incidence and impact of febrile episodes clinically associated with odontogenic infections during AC and TC chemotherapy.<br> Methods A total of 408 patients with breast cancer receiving 4 cycles of AC (n = 285) or TC (n = 123) between 2015 and 2020 were included in this single-center retrospective study. Patients recorded daily axillary temperatures and oral symptoms. Dental evaluations were performed when oral infection was suspected. Febrile episodes (≥ 37.5 °C) were assessed, and their clinical association with odontogenic infections was determined based on dental records and the documented clinical course. Relative dose intensity (RDI) was calculated to assess chemotherapy delivery.<br> Results Overall, 40.2% of patients experienced febrile episodes, and the frequency was higher in the TC group (48.8%) than the AC group (36.5%, P = 0.02). Febrile episodes associated with oral infections occurred in 9.1% of patients, of which 78.4% were clinically associated with odontogenic infections (7.1% of all patients). Most such episodes occurred during the first chemotherapy cycle (79.3%, P < 0.01). Chemotherapy RDI was reduced in three patients with febrile episodes clinically associated with odontogenic infection, but remained ≥ 85%.<br> Conclusions Febrile episodes clinically associated with odontogenic infections occurred in approximately 7%–8% of patients with breast cancer receiving perioperative AC or TC chemotherapy, predominantly during the first cycle. Odontogenic infections should be considered one possible source of febrile episodes during treatment. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1664-462X 17 2026 Quantitative resistance to Rhizoctonia solani AG-4 develops independently in leaves and roots of Brachypodium distachyon 1875734 EN Rozi Fernanda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Niranjan Mahadevan Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Natsuka Kohno School of Agriculture, Okayama University Reiko Nagao School of Agriculture, Okayama University Megumi Watanabe Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nanami Sakata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hidenori Matsui Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuhiro Toyoda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuki Ichinose Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yusuke Kouzai Crop Stress Management Group, Division of Plant Molecular Regulation Research, Institute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO) Keiichi Mochida RIKEN Center for Sustainable Resource Science Yoshiteru Noutoshi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Rhizoctonia solani is a soil-borne phytopathogen with a broad host range, classified into multiple anastomosis groups (AGs). While the rice sheath blight pathogen AG-1 IA is well-studied, defense mechanisms against AG-4, which infects diverse monocots and dicots, remain unclear. Here, we screened 153 Brachypodium distachyon accessions for resistance to AG-4 HG-I+II using both leaf and soil inoculation assays. The accessions exhibited a quantitative resistance spectrum in both assays. Some accessions were resistant to both methods, while others showed resistance in only one, indicating that leaf and root defenses operate independently. Unlike the salicylic acid (SA)-dependent resistance observed in several accessions against AG-1 IA, AG-4 leaf resistance appears to be largely SA-independent. Among 22 resistant accessions, only eight induced the SA marker BdWRKY38, whereas twelve induced the jasmonic acid (JA) marker BdAOS. Additionally, resistance in Bd3–1 was unaffected by expression of the SA hydroxylase NahG. These results are consistent with previous findings that exogenous application of SA, JA, or ethylene fails to confer AG-4 resistance. Instead, most AG-4-resistant accessions showed common upregulation of cell wall biosynthesis-related genes following leaf infection, suggesting that cell wall fortification may contribute to defense against AG-4. These findings establish B. distachyon as a valuable model for dissecting resistance mechanisms against R. solani AG-4. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1745-6215 27 1 2025 Oral health care during pregnancy to prevent preterm birth and low birth weight: study protocol for a randomized controlled trial 35 EN Junko Yasuoka Division of Global Health Sciences, Graduate School of Public Health, St. Luke’s International University Yohei Takeshita Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunsuke Okada Department of Oral and Maxillofacial Radiology, Medical Development Field, Okayama University Prodhan MD Rubayet Alam Department of Orthodontics, Dental Unit, TMSS Medical College & Rafatullah Community Hospital Akira Shibanuma Department of Community and Global Health, Graduate School of Medicine, The University of Tokyo Keiko Nanishi Office of International Academic Affairs, Graduate School of Medicine, The University of Tokyo Yoko Sato Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University Md. Zahid Hossain Department of Periodontology and Oral Pathology, Holy Family Red Crescent Medical College Hospital Musfiqa Aman Department of Periodontology, Dental Unit, TMSS Medical College & Rafatullah Community Hospital Fahmida Karim Department of Obstetrics & Gynecology, Holy Family Red Crescent Medical College Hospital Sultana Razia Department of Obstetrics & Gynecology, TMSS Medical College & Rafatullah Community Hospital Rifat Rezwana Department of Molecular and Cellular Biochemistry, Division of Oral Health, Brain Health and Total Health, Faculty of Dental Science, Kyushu University Md Mahmudur Rahman Global Communication Center, Grameen Communications Nusrat Jahan Khan Global Communication Center, Grameen Communications Naoki Nakashima Department of Medical Informatics, Graduate School of Medical Sciences, Kyushu University Rafiqul Islam Division of Healthcare Digital Transformation, Kyushu University Kimiyo Kikuchi Department of Research Promotion, Institute for Asian and Oceanian Studies, Kyushu University Background Periodontal disease during pregnancy has been associated with an increased risk of preterm birth (PTB) and low birth weight (LBW). However, most previous interventional studies have reported that scaling and root planing (SRP), a form of basic periodontal treatment, is insufficient to effectively prevent PTB and LBW. Recent systematic reviews and meta-analyses suggest that combining SRP with routine use of chlorhexidine gluconate (CHG) mouthwash may reduce the risk of these adverse birth outcomes by approximately half. This study will be among the first randomized controlled trials (RCTs) to evaluate the potential synergistic effects of this combined approach on improving birth outcomes.<br> Methods This multi-center, three-arm RCT will be conducted at two hospitals in Dhaka and Bogura, Bangladesh, between April 2025 and September 2026. A total of 480 pregnant women less than 20 weeks’ gestation attending antenatal checkups will be recruited. Participants diagnosed with periodontal disease will be randomly assigned to either an intervention group or a positive control group. Participants without periodontal disease will be assigned to a negative control group. The intervention consists of SRP combined with continued use of CHG mouthwash throughout pregnancy. The primary outcome will be the rate of PTB. Secondary outcomes include the birth weight of the newborn baby, maternal periodontal status, and oral health-related quality of life (OHRQoL). Effectiveness will be assessed by comparing outcomes across the study groups.<br> Discussion The oral health intervention is expected to improve both birth outcomes and maternal oral health. Demonstrating its effectiveness in a real-world setting may support the integration of oral health care into broader maternal, neonatal, and child health strategies, particularly in resource-limited settings.<br> Trial registration UMIN Clinical Trials Registry. UMIN000057519. Registered on April 4, 2025. https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000065719. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1756-0500 19 1 2025 Plasma expression levels of microRNA-101 are downregulated in patients with Parkinson’s disease 19 EN Tomohiro Omura Department of Pharmacy, Kobe University Hospital Hiroki Nishiguchi Department of Pharmacy, Kobe University Hospital Haruka Kaneda Department of Pharmacy, Kobe University Hospital Yumi Kitahiro Department of Pharmacy, Kobe University Hospital Kotaro Itohara Department of Pharmacy, Kobe University Hospital Kazuhiro Yamamoto Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyasu Sakane Department of Pharmaceutical Technology, Kobe Pharmaceutical University Ikuko Yano Department of Pharmacy, Kobe University Hospital Objective Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons. Endoplasmic reticulum (ER) stress contributes to PD pathogenesis, with the ER-associated degradation (ERAD) system playing a protective role. HRD1, an ER-resident ubiquitin ligase, and its stabilizer SEL1L are involved in ERAD and neuronal survival. This study investigated alterations in the plasma levels of microRNA-101 (miR-101), which targets SEL1L, in patients with PD, and its potential role as a biomarker.<br> Results Plasma miR-101 levels in patients with PD significantly decreased compared with those in healthy controls. Receiver operating characteristic curve analysis demonstrated that miR-101 could moderately discriminate patients with PD from healthy individuals (area under the curve = 0.781, 95% confidence interval = 0.547–1.00). The optimal cutoff, as determined by the Youden index, was 0.737 (expression ratio relative to that in the healthy control group), yielding a sensitivity of 50% and specificity of 100%. These results suggested that reduced plasma miR-101 expression may reflect the pathophysiological state of PD, and miR-101 has potential as minimally invasive biomarker for PD. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0289-0771 2026 Sex differences and contest experience shape walking patterns in the broad-horned flour beetle EN Kentarou Matsumura Graduate School of Arts and Sciences, The University of Tokyo Sora Hashioka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Naohisa Nagaya Faculty of Information Science and Engineering, Kyoto Sangyo University Ryusuke Fujisawa Faculty of Environmental Engineering, University of Kitakyushu, Takahisa Miyatake Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Animal movement patterns vary widely across species, and sex differences are often expected because males typically need to encounter multiple females and acquire resources. In species where males engage in male–male combat using exaggerated weapons, variation in weapon size and contest outcomes is known to influence male reproductive strategies, and may therefore also affect movement behavior. However, sex-specific and male-specific differences in locomotor behavior, particularly in relation to weapon size and social interactions, remain poorly understood. Here, we investigated walking trajectories in the broad-horned flour beetle (Gnatocerus cornutus) to test for (1) sex differences, (2) associations between male weapon size and movement behavior, and (3) the effects of male–male combat. Males exhibited more tortuous and localized movement, whereas females showed straighter and more spatially extensive trajectories. Following contests, all males showed a reduction in activity regardless of contest outcome; however, winners and losers exhibited divergent changes in movement patterns, with winners showing straighter and more spatially extensive trajectories and losers showing more tortuous and localized trajectories. In contrast, body-size-corrected weapon size was not associated with any aspect of walking behavior. These results indicate that locomotor behavior in G. cornutus varies with sex and contest experience, and that variation in walking behavior is more closely associated with social experience than with weapon morphology. No potential conflict of interest relevant to this article was reported.

岡山大学経済学会 Acta Medica Okayama 2433-4146 58 1 2026 裏表紙・英文目次 EN No potential conflict of interest relevant to this article was reported.

岡山大学経済学会 Acta Medica Okayama 2433-4146 58 1 2026 19世紀ザクセンの土地制度（６） 47 59 EN Nobushige Matsuo 10.18926/OER/70976 No potential conflict of interest relevant to this article was reported.

岡山大学経済学会 Acta Medica Okayama 2433-4146 58 1 2026 IAS41 と AASB1037 における生物の範囲設定に関する歴史的変遷 33 45 EN Kohei Yoshida 10.18926/OER/70975 No potential conflict of interest relevant to this article was reported.

岡山大学経済学会 Acta Medica Okayama 2433-4146 58 1 2026 中国における経済学アカデミック・ジョブマーケットの現状と課題 ―クラウドソーシング・データに基づくインセンティブ構造の分析― 21 32 EN Ruiting Wang 10.18926/OER/70974 No potential conflict of interest relevant to this article was reported.