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

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

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

Elsevier BV Acta Medica Okayama 2238-7854 42 2026 An electric field temporarily strengthens zirconia ceramics 1806 1810 EN Akira Kishimoto Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takahiro Shimizu Faculty of Environmental, Life, Natural Science and Technology, Okayama University Mitsuru Nishiyama Faculty of Environmental, Life, Natural Science and Technology, Okayama University Shinya Kondo Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takashi Teranishi Faculty of Environmental, Life, Natural Science and Technology, Okayama University By applying an electric field to yttria-stabilized zirconia (8YSZ) equipped with an inert electrode, oxide ions are localized near the positive electrode, causing it to expand. When polarization was performed under different conditions, it was possible to strengthen the material to 1.5 times that of an untreated sample. The lattice constant of the positive electrode surface after polarization was larger than before polarization. When the Vickers hardness of the positive electrode surface was measured by changing the test load, the smaller the load, the higher the hardness value. Polarization caused oxide ions to move near the positive electrode, filling in the defects and generating an expanded layer with a large lattice constant. It is believed that this was subjected to compressive stress from the bulk layer, which had not changed in volume, resulting in an increase in strength. No potential conflict of interest relevant to this article was reported.

岡山大学法学会 Acta Medica Okayama 0386-3050 75 3-4 2026 2024 Irish Dáil Éireann Election: An Analysis of NEDS 2024 Data 494 457 EN T. Narihiro No potential conflict of interest relevant to this article was reported.

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

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

American Chemical Society (ACS) Acta Medica Okayama 0022-2623 69 5 2026 Discovery of Thermal Sensitizers That Inhibit Heat-Induced SAFB Granule Formation 5944 5955 EN Yuji Furutani Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Natsuki Shimasaki Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Riko Yamada Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takashi Ohtsuki Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kazunori Watanabe Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Hyperthermia is a minimally invasive cancer treatment based on heat stress-induced apoptosis. Its therapeutic efficacy, however, is often limited by tumor heterogeneity and acquired thermotolerance. Therefore, combination strategies involving hyperthermia and chemotherapy have been developed to enhance the therapeutic efficacy. Previously, we showed that SB366791 enhanced heat-induced apoptosis by inhibiting heat stress-induced scaffold attachment factor B (SAFB) granule formation, although its proapoptotic activity was insufficient. Therefore, we screened to identify novel compounds that enhance heat-induced apoptosis by suppressing SAFB granule formation. We identified four hit compounds that inhibited SAFB granule formation, all exhibiting thermal enhancement ratios > 1.0─that significantly enhanced heat-induced apoptosis efficiency. Additionally, the tumor volume in mice treated with a combination of Z19024498 and hyperthermia was significantly smaller than that in mice treated with hyperthermia or Z19024498. These results indicate that the identified compounds, specifically Z19024498, have potential as thermal sensitizers for hyperthermia therapy. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1364-6753 27 1 2026 Compound heterozygosity of a novel missense variant and exonic deletion in hypomyelinating leukodystrophy 15 16 EN Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology Kenta Orimo Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology Kunihiro Ueda Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology Tomonari Seki Department of Neurology, Tokyo Teishin Hospital Yasushi Shiio Department of Neurology, Tokyo Teishin Hospital Jun Mitsui Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Harushi Mori Department of Radiology, School of Medicine, Jichi Medical University, Shoji Tsuji Institute of Medical Genomics, International University of Health and Welfare Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology Hypomyelinating leukodystrophy 15 (HLD15) results from biallelic pathogenic variants in EPRS1, but exonic deletions have not been reported. We describe a 40-year-old woman with mild intellectual disability, ataxia, dystonia, and MRI showing hypomyelination. Whole-exome sequencing identified a heterozygous missense variant in the prolyl-tRNA synthetase domain of EPRS1 (c.3430 C > G; p.Leu1144Val, NM_004446.3), without second variant. Whole-genome sequencing revealed a heterozygous 220-bp deletion spanning exon 15 (c.1743-30_1932del), and segregation analysis confirmed compound heterozygosity. RT-PCR from lymphoblastoid cells demonstrated exon-15 skipping leading to a frameshift (p.Asn582Serfs*10) and nonsense-mediated decay, leaving predominant expression of the paternally inherited missense allele. These findings support loss-of-function for the deletion and classify c.3430 C > G as likely pathogenic under ACMG/AMP criteria (PM1, PM2, PM3, PP3). This case represents the first exonic deletion reported in EPRS1. The relatively mild, adult-onset phenotype broadens both mutational and clinical spectra of HLD15 and highlights the importance of structural-variant anal No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 0916-9636 2026 Distinct associations of blood pressure phenotypes with subclinical cerebrovascular disease and coronary artery calcification in Japanese men EN Nomin Bayaraa NCD Epidemiology Research Center, Shiga University of Medical Science Yuichiro Yano NCD Epidemiology Research Center, Shiga University of Medical Science Aya Kadota NCD Epidemiology Research Center, Shiga University of Medical Science Nazar Mohd Azahar Tran Ngoc Hoang Phap National Institutes of Biomedical Innovation, Health and Nutrition Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiko Kondo NCD Epidemiology Research Center, Shiga University of Medical Science Sayuki Torii NCD Epidemiology Research Center, Shiga University of Medical Science Akira Fujiyoshi Department of Hygiene, School of Medicine, Wakayama Medical University Takayoshi Ohkubo Department of Hygiene and Public Health, Teikyo University School of Medicine Akihiko Shiino Molecular Neuroscience Research Center, Shiga University of Medical Science Kazuhiko Nozaki Department of Neurosurgery, Shiga University of Medical Science Katsuyuki Miura NCD Epidemiology Research Center, Shiga University of Medical Science Hypertension, encompassing white-coat hypertension (WCH), masked hypertension (MH), and sustained hypertension (SH), is an established risk factor for cardiovascular diseases (CVDs), including atherosclerosis. However, among the general population, findings on which target organ is affected by the different phenotypes of hypertension remain unclear. In this community-based observational study of Shiga Epidemiological Study of Subclinical Atherosclerosis, 740 Japanese men underwent brain magnetic resonance imaging to assess the presence of lacunar infarction, white-matter hyperintensities, microbleeds, and intracranial artery stenosis (ICAS) between 2012 and 2015. They also underwent office blood pressure (BP) measurements, home BP monitoring for at least five consecutive days, and coronary artery calcification (CAC) assessments between 2010 and 2014. The final analysis included 686 participants without a history of CVDs. Of the 686 participants, the mean age ( ± SD) was 68.0 ( ± 8.3) years, and 39.3% were taking antihypertensive medication. In multivariable-adjusted models, each of WCH, MH, and SH was significantly associated with a higher risk of microbleeds compared to normotension. However, the association of WCH with microbleeds was evident only among those on antihypertensive medication (adjusted odds ratio [OR] 6.75 [95% CI 1.83–24.86]) and absent in those not on such medication (adjusted OR 1.20 [95% CI 0.31–4.73]). SH was associated with lacunar infarction, ICAS, and CAC. Among Japanese men, WCH, MH, SH were associated with subclinical cerebrovascular diseases, whereas only SH was associated with CAC. Moreover, any elevated BP phenotype increased the risk of microbleeds. Our findings suggest that different hypertension phenotypes distinctly affect target organs, particularly the brain and heart. No potential conflict of interest relevant to this article was reported.

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

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

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

Elsevier BV Acta Medica Okayama 2212-4292 71 2025 A cross-sectional study of the gut microbiota associated with urinary and serum equol production status in a general population of Japanese men 107048 EN Yukiko Okami NCD Epidemiology Research Center, Shiga University of Medical Science Hisatomi Arima Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University Shigeki Bamba Department of Fundamental Nursing, Shiga University of Medical Science Fu Namai Graduate School of Agricultural Science, Tohoku University Keiko Kondo NCD Epidemiology Research Center, Shiga University of Medical Science Yuki Ideno Gunma University Center for Food Science and Wellness Ayumi Soejima Nutraceuticals Research Institute, R&D Headquarters, Nutraceuticals Division, Otsuka Pharmaceutical Co., Ltd. Haruna Miyakawa Nutraceuticals Research Institute, R&D Headquarters, Nutraceuticals Division, Otsuka Pharmaceutical Co., Ltd. Sayuki Torii NCD Epidemiology Research Center, Shiga University of Medical Science Hiroyoshi Segawa NCD Epidemiology Research Center, Shiga University of Medical Science Mizuki Ohashi NCD Epidemiology Research Center, Shiga University of Medical Science Megumi Kawashima NCD Epidemiology Research Center, Shiga University of Medical Science Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aya Kadota NCD Epidemiology Research Center, Shiga University of Medical Science Akira Sekikawa Department of Epidemiology, School of Public Health, University of Pittsburgh Akira Fujiyoshi Department of Hygiene, Wakayama Medical University Katsuyuki Miura NCD Epidemiology Research Center, Shiga University of Medical Science SESSA Research Group Equol is a metabolite produced by the gut microbiota from the soy isoflavone daidzein. Previous studies identified bacteria capable of converting daidzein to equol. We investigated whether equol producers among Japanese with a high soy intake contained these bacteria. We also examined differences in equol production status between urine and serum and how the gut microbiota differs between these statuses. To minimize the potential confounding effects of hormonal variability in women, this cross-sectional study analyzed 853 Japanese men. Urinary and serum isoflavones were collected in the morning after fasting and were analyzed using LC-MS/MS. By applying a finite mixture model for each log10 equol/daidzein ratio, we defined equol producers and non-producers from urine and serum. Among 669 participants with fecal microbial measurements, the 16S rRNA gene was sequenced on a MiSeq System. The cut-off values for the log10 equol/daidzein ratio were −0.94 for urine and −0.95 for serum. Equol production status in urine and serum matched in 97 %, and equol producers from urine or serum were 42 %. The microbiota was more diverse in producers than in non-producers; the genus Senegalimassilia included strains with high sequence identity (>98 %) to daidzein reductase. The family Oscillospiraceae and class Clostridia also had approximately 46 %–48 % sequence identity. The equol production status of fasting urine and serum almost matched among a general population of Japanese men. Although we did not detect a microbiota with known daidzein reductase in equol producers, several shared similar sequences; these may include equol-producing bacteria that have not yet been identified. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 2639-8028 8 2 2026 Association Between Positive End-Expiratory Pressure at Venovenous Extracorporeal Membrane Oxygenation Initiation and Liberation Outcomes in Acute Respiratory Distress Syndrome: A Multicenter Retrospective Study e1375 EN Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yoshinori Kosaki Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Mitsuaki Nishikimi Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Shinichiro Ohshimo Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Nobuaki Shime Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University IMPORTANCE: The optimal level of positive end-expiratory pressure (PEEP) during venovenous extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) remains uncertain.<br> OBJECTIVES: This study aimed to evaluate the association between initial PEEP settings at ECMO initiation and the rate of successful ECMO liberation in patients with severe ARDS.<br> DESIGN, SETTING, AND PARTICIPANTS: We conducted a post hoc analysis of the multicenter Japan Chest CT for ARDS Requiring Venovenous ECMO (J-CARVE) registry. Adult patients with severe ARDS treated with venovenous ECMO between 2012 and 2022 at 24 institutions were included. Participants were categorized into three groups according to PEEP at ECMO initiation: low (< 8 cm H2O), middle (8–10 cm H2O), and high (> 10 cm H2O).<br> MAIN OUTCOMES AND MEASURES: The primary outcome was successful liberation from ECMO within 30 days. Multivariable Cox proportional hazards models were used to evaluate associations. Secondary outcomes included 60-day mortality, duration of ECMO support, and duration of mechanical ventilation.<br> RESULTS: Among 683 patients analyzed, the overall ECMO liberation rate at 30 days was 69.2%. Liberation rates were 57.8% (103/178), 73.5% (259/352), and 72.5% (111/153) in the low, middle, and high PEEP groups, respectively. After adjustment, the low group had a significantly lower likelihood of successful ECMO liberation (hazard ratio [HR], 0.56; 95% CI, 0.39–0.81) compared with the middle group. No significant difference was observed between the high and middle groups (HR, 0.80; 95% CI, 0.58–1.10). The low group had longer ECMO duration; however, 60-day mortality and hospital length of stay did not differ significantly among groups.<br> CONCLUSIONS AND RELEVANCE: Lower PEEP levels at ECMO initiation were associated with reduced likelihood of successful ECMO liberation compared with moderate PEEP, whereas estimates for high vs. moderate PEEP were not statistically significant. These findings support avoiding insufficiently low PEEP and underscore the need for prospective studies to refine optimal PEEP strategies in patients with severe ARDS. No potential conflict of interest relevant to this article was reported.

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

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

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

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

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

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

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

Elsevier BV Acta Medica Okayama 1156-5233 35 2 2025 Cerebellar abscess caused by Cladophialophora bantiana involving an elderly Japanese woman 101548 EN Kenta Nakamoto Department of Infectious Diseases, Okayama University Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Kohei Oguni Department of Infectious Diseases, Okayama University Hospital Yukika Yokoyama Microbiology Division, Clinical Laboratory, Okayama University Hospital Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Shuichiro Hirano Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Yaguchi Division of Clinical Research, Medical Mycology Research Center Sayaka Ban Division of Clinical Research, Medical Mycology Research Center Akira Watanabe Division of Clinical Research, Medical Mycology Research Center Hiroki Okunobu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuhito Suyama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Marina Kawaguchi Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yousuke Sazumi Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Phaeohyphomycosis is a rare fungal infection that presents significant challenges in diagnosis and treatment. Herein, we document a case of a cerebellar abscess caused by Cladophialophora bantiana. A 77-year-old woman with type 2 diabetes mellitus and a previous history of diffuse large B-cell lymphoma gradually developed ataxia and was transferred to an emergency department. Head imaging investigations indicated a cerebellar mass and the patient underwent an emergent endoscopic drainage. Although bacterial cultures of the drainage specimen yielded no growth, a dematiaceous fungus was isolated and subsequently identified as C. bantiana through ITS sequencing analysis. The patient received antifungal combination therapy, initially with liposomal amphotericin B and voriconazole, and finally posaconazole and 5-fluorocytosine. Brain abscesses caused by C. bantiana are rarely documented, and an optimal treatment strategy has yet to be established. Given the high fatality rate, an early surgical intervention is crucial for both diagnosis and treatment. The present case was successfully treated with minimally invasive surgical intervention alongside the antifungal combination therapy. No potential conflict of interest relevant to this article was reported.

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

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

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

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

岡山医学会 Acta Medica Okayama 0030-1558 137 3 2025 備前市における新型コロナウイルス感染症の抗体検査に関する研究の成果報告 118 125 EN Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University Ayako Sasaki Kurashiki City Public Health Center Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University Tomoka Kadowaki Center for Public Health Action in Applied Epidemiology, National Institute of Infectious Diseases Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Soshi Takao Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University 　We conducted two prospective cohort studies (June 2022–March 2023 and Nov 2023–Jan 2024) of 1,899 and 445 residents and other individuals who are affiliated with institutions in the city of Bizen in Japan's Okayama prefecture (population 32,320 as of 2020). We measured the subjects' titers of antibodies against SARS-CoV-2, evaluated changes in their antibody titers, and assessed the associations of the titers with the subjects' vaccination status, infection, and COVID-19 status/severity. This report summarizes the two studies' findings. These prospective studies based on a wide age range in a general population provide information that can be used to determine the appropriate timing of vaccination during a pandemic. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 2949-7744 3 2025 Efficient variant phasing utilizing a replication cycle reaction system 103457 EN Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Jun Mitsui Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Shoji Tsuji Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Purpose: When 2 heterozygous variants are detected in autosomal recessive disease genes, determining whether they are in cis or in trans is essential. Subcloning polymerase chain reaction products or complementary DNA is limited by variant distance (up to 10 kb) and complementary DNA availability. Droplet digital polymerase chain reaction, effective up to 100 kb, faces probe design challenges. We used replication cycle reaction (RCR), which replicates large DNA fragments based on E. coli chromosome replication, to phase widely spaced heterozygous variants.<br> Methods: Circular DNA molecules were formed by ligating CRISPR/Cas9-cleaved genomic fragments with an oriC-AmpR cassette, then amplified by RCR. Using a genomic DNA (gDNA) sample that is previously analyzed by long-read sequencing, we optimized reaction conditions (including gDNA to oriC-AmpR cassette ratios) and validated phasing accuracy via electrophoresis and Sanger sequencing. Finally, we applied this method to 7 patients harboring 2 heterozygous pathogenic variants (4.3-152 kb apart).<br> Results: RCR amplified genomic regions up to 104 kb. Lower gDNA-to-cassette ratios favored monoallelic amplification, enabling straightforward phasing, whereas higher ratios yielded biallelic products requiring transformation-based allele separation. For variants 152 kb apart, an intervening single-nucleotide variant enabled phased reconstruction. Ultimately, RCR confirmed compound heterozygosity in all 7 patients.<br> Conclusion: This method effectively phases multiple heterozygous variants across large genomic distances. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 2167-8421 2025 Novel in-frame duplication variant of SOD1 in a Japanese family with familial amyotrophic lateral sclerosis EN Masanori Nakajima Department of Neurology, Kyorin University School of Medicine Hiroya Naruse Department of Neurology, Graduate School of Medicine, The University of Tokyo Yuichi Riku Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Kunihiro Ueda Department of Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Jun Mitsui Department of Neurology, Graduate School of Medicine, The University of Tokyo Yoshitsugu Nakamura Division of Neurology, Department of Internal Medicine IV, Osaka Medical and Pharmaceutical University Shimon Ishida Division of Neurology, Department of Internal Medicine IV, Osaka Medical and Pharmaceutical University Takashi Yamada Department of Pathology, Osaka Medical and Pharmaceutical University Naoki Moro Department of Neurology, Kyorin University School of Medicine Naoki Kotsuki Department of Neurology, Kyorin University School of Medicine Kentaro Nagai Department of Neurology, Kyorin University School of Medicine Shin-ichi Tokushige Department of Neurology, Kyorin University School of Medicine Ayumi Uchibori Department of Neurology, Kyorin University School of Medicine Chizuko Oishi Department of Neurology, Kyorin University School of Medicine Hiroyuki Yabata Department of Neurology, Shiga University of Medical Science Makoto Urushitani Department of Neurology, Shiga University of Medical Science Yasushi Iwasaki Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Hiroyuki Ishiura Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 Yaeko Ichikawa Department of Neurology, Kyorin University School of Medicine Objectives: To analyze the cases of a family with a novel in-frame duplication variant (NM_000454.5:c.357_357 + 2dup, p.Val120dup) of SOD1 and a structural model of the mutated SOD1 protein. Methods: The clinical profiles of three patients in the family were analyzed, including the neuropathological findings of the proband’s mother. Genetic analyses were conducted for three patients. cDNA and in silico structural analyses were performed to evaluate the effects of duplication variants on the structure of SOD1. Results: The clinical features of the patients included predominant involvement of the lower motor neurons, asymmetric onset of motor symptoms in the lower limbs, and a relatively rapid progression of muscular weakness and respiratory insufficiency. Neuropathological findings revealed severe loss of spinal cord motor neurons, and immunohistochemistry using an anti-misfolded SOD1 antibody revealed aggregates in the spinal cord. Genetic analyses revealed a c.357_357 + 2dup at the exon 4–intron 4 boundary of SOD1 in three patients. cDNA analysis of the proband suggested the presence of a valine (p.Val120dup) duplication in the heterozygous state, and the SOD1 transcript level showed no significant differences from those of healthy controls. In silico structural analyses predicted that p.Val120dup could affect the structure of the β-barrels and copper ion binding site of SOD1, suggesting an abnormal conformation of SOD1 that is predicted to interfere with the binding of copper ions. Conclusion: We identified a novel in-frame duplication variant in the C-terminus of β7 of SOD1. This genotype–structure–phenotype study of SOD1 provides valuable insights into disease-causing mechanisms. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2328-9503 2025 Dorsolateral Cervical Cord T2 Hyperintensity in KIF1C-Related Disease (Spastic Paraplegia 58): Two Long-Duration Cases EN Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo Masao Osaki Department of Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Miho Osako Department of Neurology, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled Chisen Takeuchi Department of Neurology, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Jun Mitsui Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Ryo Kurokawa Department of Radiology, Graduate School of Medicine, The University of Tokyo Harushi Mori Department of Radiology, School of Medicine, Jichi Medical University Yuji Takahashi Department of Neurology, Graduate School of Medicine, The University of Tokyo Jun Goto Department of Neurology, Graduate School of Medicine, The University of Tokyo Shoji Tsuji Institute of Medical Genomics, International University of Health and Welfare Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Pathogenic variants in KIF1C cause Spastic Paraplegia 58 (SPG58), typically presenting with cerebellar ataxia and spastic paraparesis. We report two unrelated patients with spastic paraparesis, cerebellar ataxia, and tremor. Whole-exome sequence analysis identified novel homozygous variants in the motor domain of KIF1C (NM_006612.6): c.921G>A (p.Trp307Ter) and c.607C>T (p.Arg203Trp). In addition to the canonical brain MRI showing leukoencephalopathy with posterior dominance and hyperintensity along the corticospinal tracts, both patients showed symmetric T2 hyperintensity confined to the lateral and dorsal columns of the cervical cord. Given the long disease durations (22 and 51 years), these findings may represent late-emerging or previously overlooked spinal cord involvement and broaden the neuroradiological spectrum of SPG58. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0969-806X 237 2025 Impact of different X-ray tube positions on actual dose measurements during CT examinations -An effect of patient physique- 113001 EN Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University Tatsuya Maeda Graduate School of Medical Sciences, Kanazawa University Kazuki Takegami Department of Radiological Technology, Yamaguchi University Hospital Sota Goto Faculty of Health Sciences, Kobe Tokiwa University Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Daiki Kobayashi Graduate School of Medical Sciences, Kanazawa University Yuki Kanazawa Faculty of Life Science, Kumamoto University Kazuta Yamashita Department of Orthopedics, School of Medicine, Tokushima University Takeshi Konishi MEDITEC JAPAN Co., Ltd. Motochika Maki MEDITEC JAPAN Co., Ltd. Dose management of patients is very important during X-ray Computed Tomography (CT) examinations, but because the patient's surface dose is inhomogeneous, it is difficult to measure the most probable value using a small passive-type dosimeter, lent to the patient. To solve this problem, our research group developed a precise dose analysis procedure in which a systematic uncertainty related to the X-ray incident direction (θin) is reduced. θin information was analyzed from CT images. However, the applicability of our procedure to actual patients with various physiques has not been examined. This study aims to propose a dose analysis procedure that can be applied to patients with various physiques, and to show its impact on dose measurement. Clinical data of 198 patients with Body Mass Index (BMI) values between 15 and 40 kg/m2 (mean value: 23.1 ± 3.8 kg/m2) who underwent chest CT scans were analyzed after dividing them into three groups based on BMI values. The absorbed dose was measured with a small-type Optically Stimulated Luminescence (OSL) dosimeter. To derive correction factors related to θin, the dependence of the actually-measured dose values of various patients on θin was analyzed. The correction coefficients were determined independently for the three groups classified by BMI values. By correcting the effect of θin, the systematic uncertainty element could be reduced, resulting in 30 % reduction of the uncertainty. Furthermore, it was found that our analysis procedure makes it possible to visualize outliers. In comparison with the expected dose values based on Computed Tomography Dose Index (CTDI) values, most of the data fell within the range of ±1.34 mGy (=1σ). However, 7 % of the data showed large deviations larger than 2σ. In conclusion, our research group has developed a procedure for measuring patient surface doses that can be applied to patients having various physiques, in which the effects of X-ray incident direction were accurately corrected. The procedure could be one solution to the problems with actual dose measurements during CT examinations, and will be useful for dose management based on the small-type dosimeter. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0169-555X 493 2026 Coast uplifted by nearby shore-parallel active submarine faults during the 2024 Mw 7.5 Noto Peninsula earthquake 110069 EN Hideaki Goto Hiroshima University Tomoru Yamanaka Natural History Museum and Institute Chiba Tomohiro Makita Hiroshima University Yoshiya Iwasa University of Teacher Education Fukuoka Takuro Ogura Hyogo University of Teacher Education Kyoko Kagohara Yamaguchi University Yasuhiro Kumahara Hiroshima University Yasuhiro Suzuki Nagoya University Nobuhisa Matta Okayama University Tatsuto Aoki Kanazawa University Wataru Mori Hiroshima University Kenta Haranishi Hiroshima University Takashi Nakata Hiroshima University An Mw 7.5 earthquake occurred at 16:10 JST on January 1, 2024 at a depth of 16 km on the Noto Peninsula, central Japan. This earthquake was the second-largest intraplate earthquake recorded in Japan during 120 years of seismic observation, and it caused approximately 100 km of coastal seafloor emergence along the peninsula's northern coast. Herein, we mapped the emergence of this coastal seafloor and measured the uplift along the coast. The movement of the coastline led to the emergence of approximately 4.4 km2 of seafloor, which is continuous and probably the longest in the world. We determined the uplift distribution along the coast using the white remains of a reddish seaweed called Corallina pilulifera. Its upper limit exhibited a distinct horizontal line, effectively representing the uplift amount throughout the peninsula. Two large, uplifted regions were identified, around Cape Saruyama (5.21 m) in the west and Cape Kurasaki (2.70 m) in the north. Although active offshore submarine faults have been extensively researched, the fault traces remain poorly defined because they are primarily interpreted from seismic reflection profiles. We identified the distribution of active submarine faults using anaglyph-type stereoscopic images, confirming the subsurface deformation structure seen through the seismic reflection profiles. The main fault trace is primarily straight and contiguous with the nearby north coast. The uplift amount is greater near the active fault traces on the north side and diminishes sharply with increasing distance from these faults, indicating a southward tilt of surface uplift related to the active submarine faults. No potential conflict of interest relevant to this article was reported.

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

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

Oxford University Press (OUP) Acta Medica Okayama 1465-3621 55 5 2025 Multicenter, open-label, randomized, controlled study to test the utility of electronic patient-reported outcome monitoring in patients with unresectable advanced cancers or metastatic/recurrent solid tumors 547 555 EN Naruto Taira Department of Breast and Thyroid Surgery, Kawasaki Medical School Naomi Kiyota Department of Medical Oncology and Hematology, Cancer Center, Kobe University Hospital Yuichiro Kikawa Department of Breast Surgery, Kansai Medical University Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Kyoko Kato Department of Medical Oncology, National Hospital Organization Nagoya Medical Center Kaoru Kubota Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Ryosuke Tateishi Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo Akinobu Nakata Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine Keiichiro Nakamura Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukiya Narita Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Hiroji Iwata Department of Advanced Clinical Research and Development, Nagoya City University Akihiko Gemma Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Kojiro Shimozuma Department of Biomed Sciences, College of Life Sciences, Ritsumeikan University Kei Muro Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine Tetsuya Iwamoto Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Yuki Takumoto Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Takeru Shiroiwa Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Takashi Fukuda Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health Takuhiro Yamaguchi Division of Biostatistics, Tohoku University Graduate School of Medicine Yasuhiro Hagiwara Department of Biostatistics, Division of Health Sciences and Nursing, The University of Tokyo Graduate School of Medicine Hironobu Minami Division of Medical Oncology and Hematology, Department of Medicine, Kobe University Graduate School of Medicine Electronic patient-reported outcome (ePRO) monitoring for patients undergoing cancer chemotherapy may provide qualified and early detection of adverse events or disease-related symptoms, leading to improved patient care. The aim of this study is to examine whether addition of ePRO monitoring to routine medical care contributes to improved overall survival and quality of life of cancer patients undergoing chemotherapy. Patients with unresectable advanced cancers or metastatic/recurrent solid tumors receiving systemic chemotherapy will be randomized to an ePRO monitoring group and a usual care group. The ePRO group will conduct weekly symptom monitoring using an electronic device after study enrollment until the end of the study. Monitoring results will be returned to medical personnel and used as information for patient care. The primary endpoints are overall survival and health related quality of life. The initial target sample size for the study was 1500 patients. However, due to delays in enrollment, the target was readjusted to 500 patients. Enrollment has been completed, and the study is now in the follow-up phase. No potential conflict of interest relevant to this article was reported.

Georg Thieme Verlag KG Acta Medica Okayama 0013-726X 57 S 01 2025 Underwater endoscopic papillectomy of a duodenal adenoma extending to the papilla using a forward-viewing endoscope E667 E668 EN Takashi Yamamoto Department of Gastroenterology, Okayama University Hospital Yasushi Yamasaki Department of Gastroenterology, Okayama University Hospital Yuki Fujii Department of Gastroenterology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 1350-4487 191 2026 Experimental approach of internal dose map visualization during helical CT examinations: importance of X-ray incident direction analysis and central internal dose estimation 107586 EN Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University Kazuki Takegami Department of Radiological Technology, Yamaguchi University Hospital Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Daiki Kobayashi Graduate School of Medical Sciences, Kanazawa University Sota Goto Faculty of Health Sciences, Kobe Tokiwa University Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Masaki Takemitsu Department of Radiological Technology, Yamaguchi University Hospital Rin Ishii College of Transdisciplinary Sciences for Innovation, Kanazawa University Shinichi Morimoto Meditec Japan Co., Ltd. Motochika Maki Meditec Japan Co., Ltd. During computed tomography (CT) examination, radiation exposures should be appropriately managed taking into considering the effects of bowtie filter, the heel effect and over-beaming effect. Furthermore, the analysis of an X-ray incident direction is important. The purpose of this study is to develop a procedure to obtain two-dimensional (2D) internal dose distributions based on actual measurements of surface dose distribution and central internal dose data. Experiments were conducted using a clinical CT scanner and four cylindrical polyacetal resin (POM) phantoms having diameters of 15–30 cm. The entrance surface doses and the central internal dose were measured by placing the optically stimulated luminescence (OSL) dosimeters on the surface and inner part of the phantom, respectively, during helical CT scans. The X-ray incident direction at the slice containing the dosimeter was estimated based on the noise distribution analysis of the CT image. Then, circumferential surface dose distributions were determined as a function of the X-ray incident direction. Based on these experimental data, we succeeded in visualizing the 2D dose distributions. The obtained dose distribution was inhomogeneous, clearly reflecting the influence of factors such as the heel effect. The uncertainty due to our methodology was estimated to be from 4.3 % to 7.4 %. Our methodology needs central internal dose data, and the absence of this data introduced additional systematic uncertainties of +6.9 % to −11.4 %. In conclusion, correcting for the effect of the X-ray incident directions for entrance surface dose and adding the central inner dose data can improve the reliability of the internal dose distribution. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1350-4487 191 2026 A novel wearable dosimeter system that can analyze the incident direction of X-rays for medical dosimetry – Improvements to the detector arrangements and analysis algorithm – 107592 EN Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Daiki Kobayashi Graduate School of Medical Sciences, Kanazawa University Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Sota Goto Faculty of Health Science, Kobe Tokiwa University Kazuki Takegami Department of Radiological Technology, Yamaguchi University Hospital Rin Ishii College of Transdisciplinary Sciences for Innovation, Kanazawa University Mana Mitani Division of Radiological Technology, Medical Support Department, Okayama University Hospital Mitsugi Honda Division of Radiological Technology, Medical Support Department, Okayama University Hospital Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University When performing real-time dosimetry using an active-type dosimeter during clinical fluoroscopic procedures, angular dependence of dosimeter response should be taken into account. Our research group addressed this issue and proposed a triple-type dosimeter that can determine the incident angle of scattered X-rays. The triple-type detector consists of three active dosimeters. The two side dosimeters have slope filters to enhance the angular dependence and are intentionally tilted. The central dosimeter faces forward. The incident angle of X-rays (θin) is estimated using the signal differences between the central dosimeter and the left and/or right dosimeters. Then, the absolute dose is determined by correcting the angular dependence of the central dosimeter based on the estimated θin. In order to verify the concept of the triple-type dosimeter, we conducted a proof-of-concept experiment using clinical X-ray fluoroscopic equipment. Scattered X-rays were generated by irradiating an elliptical cylindrical water phantom. The response of the triple-type dosimeter was evaluated by rotating it to vary the incident angle of scattered X-rays generated by the water phantom. The proposed dosimetry system could estimate the θin over an angular range of ±80° (with uncertainty of 1.35°), which is 30° wider than the previous version, and successfully determined the absolute doses after correction for the angular dependence of the dosimeter. Although the active-type dosimeter had a systematic uncertainty related to the angular dependence of ±15.2 %, our system succeeded in reducing the systematic uncertainty to ±3.2 %. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2666-5204 26 2025 Characteristics of out-of-hospital cardiac arrest due to cerebrovascular disorders: a nationwide, retrospective, observational study 101145 EN Yoshiyuki Ueda Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Tsuyoshi Nojima Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Takafumi Obara Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Takashi Hongo Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Tetsuya Yumoto Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Kohei Tsukahara Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Takashi Yorifuji Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Epidemiology Atsunori Nakao Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Hiromichi Naito Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Background: Data on out-of-hospital cardiac arrest (OHCA) due to cerebrovascular disorders is limited. This study aimed to describe the characteristics, outcomes, and annual trends of outcomes for OHCA originating from cerebrovascular disorders.<br> Methods: This study was a retrospective analysis using an Utstein-style Japanese National Registry. Adult patients with OHCA due to cerebrovascular disorders and transported to the hospital between 2005 and 2021 were included. The primary outcome was a favorable neurological outcome at 30-day. We analyzed factors associated with outcomes using a multivariable logistic regression model, then evaluated annual trends of outcomes for cerebrovascular-induced OHCA.<br> Results: Among 2,081,023 OHCA patients, 52,969 had cerebrovascular-induced cardiac arrest. Of these, 1903 (3.5 %) achieved a favorable neurological outcome. In the multivariable logistic regression model, male sex (adjusted odds ratio [aOR] 1.41, 95 % confidence interval [CI] 1.20–1.61), initial shockable rhythm (aOR 3.10, 95 % CI 2.18–4.40), witnessed cardiac arrest (aOR 1.92, 95 % CI: 1.57–2.34), and prehospital return of spontaneous circulation (ROSC) (aOR 11.1, 95 % CI: 9.09–13.5) were associated with favorable neurological outcomes. Prehospital adrenaline administration was negatively associated with favorable neurological outcomes (aOR 0.22, 95 % CI: 0.16–0.30). The proportion of patients with favorable neurological outcomes increased over time, rising from 3.14 % in 2005 to 4.12 % in 2021.<br> Conclusions: Although OHCA due to cerebrovascular disorders is generally associated with poor neurological outcomes, 3.5 % of the patients with cerebrovascular-induced OHCA in this study had favorable neurological outcomes, with a yearly trend improving over decades. Patient characteristics associated with a higher likelihood of a favorable neurological outcome included prehospital ROSC, initial shockable rhythm, and witnessed cardiac arrest. 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 Association between gestational age and child health and neurodevelopment in twins from a nationwide longitudinal survey in Japan 40608 EN Kei Tamai Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihito Takeuchi Division of Neonatology, NHO Okayama Medical Center Makoto Nakamura Division of Neonatology, NHO Okayama Medical Center Misao Kageyama Division of Neonatology, NHO Okayama Medical Center Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Despite previous research, evidence on the relationship between gestational age and long-term health and neurodevelopmental outcomes among twins remains limited. Using data from the Longitudinal Survey of Babies in the 21st Century, we analyzed 549 twins born in Japan in 2010. The twins were grouped by gestational age: <32 weeks (very preterm), 32–36 weeks (moderately and late preterm), and 37–38 weeks (early term). The health status was evaluated by hospitalization between 0.5 and 5.5 years, and behavioral development was assessed using questionnaires at 2.5 and 5.5 years. Binomial log-linear regression with generalized estimating equations accounted for within-pair correlations and adjusted for child and parental variables. Moderately and late preterm children showed a higher risk of all-cause hospitalization during infancy than early-term children (adjusted risk ratio, 1.7; 95% CI, 1.0–2.6). Very preterm children showed a higher point estimate of the risk ratio, but a wide CI (risk ratio, 2.3; 95% CI, 0.8–6.8). Behavioral delays were more common in preterm groups at 2.5 years but not at 5.5 years. Preterm twins have a higher risk of hospitalization during infancy and developmental delay at 2.5 years than early-term twins. These risks show an increasing trend as gestational age decreases. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 10 2025 Association of Use of GRADE, Protocol Registration, and Journal Impact Factor With Reporting and Methodological Quality of Systematic Reviews Published in Rehabilitation Journals: A Meta-Epidemiological Study e95695 EN Takahiro Tsuge Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Norio Yamamoto Systematic Reviewers, Scientific Research WorkS Peer Support Group (SRWS-PSG) Yosuke Tomita Physical Therapy, Faculty of Health Care, Takasaki University of Health and Welfare Akikazu Hagiyama Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daijo Shiratsuchi Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University Masatsugu Okamura Systematic Reviewers, Scientific Research WorkS Peer Support Group (SRWS-PSG) Takao Kaneko Rehabilitation, Yamagata Prefectural Central Hospital Kosuke Suzuki Rehabilitation, Yamagata Saisei Hospital Yuki Nakashima Systematic Reviewers, Scientific Research WorkS Peer Support Group (SRWS-PSG) Shunsuke Taito Systematic Reviewers, Scientific Research WorkS Peer Support Group (SRWS-PSG) Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University This study aimed to identify factors associated with the reporting and methodological quality of systematic reviews (SRs) published in rehabilitation journals. We conducted a meta-epidemiological study as a secondary analysis of a previous study. The study protocol was registered in the Open Science Framework. We analyzed 219 SRs from rehabilitation journals published since 2020. We assessed reporting quality using the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 and methodological quality using A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2. Multiple linear regression and Spearman's correlation were used to identify factors associated with quality, including Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and the Journal Impact Factor (JIF). Multivariate analysis revealed PRISMA 2020 adherence was significantly associated with use of GRADE (β = 4.33; 95% confidence interval (CI): 3.24-5.42), protocol registration (β = 3.40; 95% CI: 2.32-4.47), and the JIF (2023) (β = 0.69; 95% CI: 0.42-0.95). AMSTAR 2 adherence was also significantly associated with use of GRADE (β = 2.52; 95% CI: 1.88-3.17), protocol registration (β = 2.07; 95% CI: 1.44-2.70), and the JIF (2023) (β = 0.29; 95% CI: 0.14-0.45). Weak positive correlations were observed between the JIF (2023) and both PRISMA 2020 and AMSTAR 2 adherence (ρ = 0.27 and ρ = 0.22, respectively; both P < 0.01). It should be noted that these findings reflect associations and do not imply causality. To enhance the quality of SRs in rehabilitation, researchers should prioritize adherence to PRISMA 2020, particularly the use of GRADE and protocol registration, which this study identified as key associated factors. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-3921 14 12 2025 Roles of ROS and NO in Plant Responses to Individual and Combined Salt Stress and Waterlogging 1455 EN Taufika Islam Anee Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University Nasser A. Sewelam Botany Department, Faculty of Science, Tanta University Nonnatus S. Bautista Institute of Biological Sciences, College of Arts and Sciences, University of the Philippines Los Baños Takashi Hirayama Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University During the climate change era, plants are increasingly exposed to multiple environmental challenges occurring simultaneously or sequentially. Among these, salt stress and waterlogging are two major factors that severely constrain crop productivity worldwide and often occur together. To survive under such conditions, plants have evolved sophisticated systems to scavenge harmful levels of reactive oxygen species (ROS). Despite their cytotoxic potential, ROS also act as key signaling molecules that interact with nitric oxide (NO), Ca2+, protein kinases, ion homeostasis pathways, and plant hormones. These signaling and acclimatory mechanisms are closely associated with the functions of energy-regulating organelles―chloroplasts and mitochondria―which are major sources of ROS under both individual and combined stresses. While many of these responses are shared between salt stress, waterlogging and their combination, it is likely that specific signaling mechanisms are uniquely activated when both stresses occur together―mechanisms that cannot be inferred from responses to each stress alone. Such specificity may depend on precise coordination among organelle-derived signals and the tight regulation of their cross-communication. Within this network, ROS and NO likely serve as central hubs, fine-tuning the integration of multiple signaling pathways that enable plants to adapt to complex and fluctuating stress environments. 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 Mid-term Clinical and Radiographic Outcomes of the Actis Total Hip System: A Retrospective Study e77632 EN Yasutaka Masada Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomonori Tetsunaga Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuki Yamada Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Koura Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Inoue Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuichiro Okuda Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoko Tetsunaga Department of Orthopaedic Surgery, Okayama University Hospital Yusuke Yokoyama Department of Orthopaedic Surgery, Okayama University Hospital Yuki Okazaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Introduction<br> Implant technology for total hip arthroplasty (THA) was developed to improve hip function and patient satisfaction. Actis (DePuy Synthes, Warsaw, IN, USA) is a short fit-and-fill titanium stem, with a medial-collared and triple-taper (MCTT) geometry, that is fully coated with hydroxyapatite (HA). We evaluated the radiographic and clinical outcomes of the Actis Total Hip System during a mean follow-up of five years.<br> Patients and methods<br> We retrospectively analyzed data from 80 patients (14 male and 66 female, mean age: 65 ± 8.4 years) who underwent primary THA using Actis stems (anterolateral approach, 60 hips; posterior approach, 20 hips). Radiographs were obtained postoperatively and at the time of the final examination. Radiographic assessments included the alignment of the femoral stem, spot welds, stress shielding, cortical hypertrophy, subsidence (>2 mm), radiolucent line, pedestal formation, Dorr type, canal fill ratio (CFR), and stem fixation. Clinical evaluation included the Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire (JHEQ) and Harris Hip Score (HHS).<br> Results<br> The mean follow-up period was 64.0 ± 6.0 months. No significant differences were observed in the alignment of the femoral components between approaches. Of the 80 hips, 53 (66.3%) showed radiographic signs of stem osseointegration, predominantly in the mid-distal region of the stem at the final follow-up. Multiple logistic regression analysis revealed that younger age and a higher CFR (20 mm proximal to the lesser trochanter) were associated with the presence of spot welds. Mild stress shielding occurred in 25 hips (31.3%), and no patient experienced severe stress shielding. All stems were fixed by bone on growth. The JHEQ and HHS significantly improved at the final assessment.<br> Conclusion<br> At the five-year follow-up, patients who received the Actis Total Hip System during THA had good radiographic and clinical outcomes.<br> No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1434-3916 145 1 2025 Changes in the anatomical positions of the femoral nerve and artery in the lateral and supine positions: a multicenter retrospective study 373 EN Ryuichiro Okuda Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tomonori Tetsunaga Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuki Yamada Department of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoko Tetsunaga Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Koura Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tomohiro Inoue Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasutaka Masada Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tetsuya Yamamoto Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shin Matsumoto Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hisanori Ikuma Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital Tadashi Komatsubara Department of Orthopaedic Surgery, Okayama Rosai Hospital Yuki Okazaki Department of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Introduction Femoral nerve palsy and femoral artery injury are serious complications of total hip arthroplasty. However, few studies have compared the anatomical positions of these structures in different patient positions. This study aimed to compare the anatomical positions of the femoral nerve and artery in the lateral and supine positions.<br> Materials and methods This multicenter retrospective study included 111 patients who underwent lateral and supine computed tomography (CT) from 2016 to 2023. CT images were reconstructed in the anterior pelvic plane. The horizontal distance from the anterior margin of the acetabulum to the femoral nerve (Distance N) and femoral artery (Distance A) was measured. The difference in Distance N between the two positions (ΔLateral–supine Distance N) was calculated by subtracting the supine value from the lateral value.<br> Results The average Distance N was 26.5 ± 5.1 mm in the lateral position and 21.1 ± 4.4 mm in the supine position, with the nerve located significantly closer to the acetabulum in the supine position (P < 0.001). Similarly, the average Distance A was 26.8 ± 5.4 mm in the lateral position and 20.4 ± 4.9 mm in the supine position (P < 0.001). Multiple regression analysis showed that Distance N in the lateral position was significantly shorter in female patients and those with low body weight. In addition, low body weight correlated with a smaller ΔLateral–supine Distance N.<br> Conclusions The femoral nerve and artery are located closer to the anterior margin of the acetabulum in the supine position than in the lateral position. Low body weight was an independent predictor of shorter Distance N in both positions and a smaller ΔLateral–supine Distance N. These findings underscore the importance of considering patient positioning during total hip arthroplasty, particularly in patients with low body weight, to reduce neurovascular risks. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1648-9144 61 6 2025 Accuracy Verification of a Computed Tomography-Based Navigation System for Total Hip Arthroplasty in Severe Hip Dysplasia: A Simulation Study Using 3D-Printed Bone Models of Crowe Types II, III, and IV 973 EN Ryuichiro Okuda Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomonori Tetsunaga Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuki Yamada Department of Orthopaedic Surgery, Okayama University Hospital Tomoko Tetsunaga Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Koura Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Inoue Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasutaka Masada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background and Objective: The use of computed tomography (CT)-based navigation systems has been shown to improve surgical accuracy in total hip arthroplasty. However, there is limited literature available about the application of CT-based navigation systems in severe hip dysplasia. This study aimed to evaluate the accuracy of a CT-based navigation system in patients with severe hip dysplasia using three-dimensional (3D)-printed bone models. Methods: 3D-printed bone models were generated from CT data of patients with severe hip dysplasia (Crowe type II, 10 hips; type III, 10 hips; and type IV, 10 hips). The accuracy of automatic segmentation, success rate, point-matching accuracy across different registration methods, and deviation values at reference points after registration were assessed. Results: For the combined cohort of Crowe II, III, and IV cases (n = 30), the Dice Similarity Coefficient and Jaccard Index were 0.99 ± 0.01 and 0.98 ± 0.02, respectively. These values indicate a high level of segmentation accuracy. The “Matching with true and false acetabulum + iliac crest” method achieved a 100% success rate across all groups, with mean deviations of 0.08 ± 0.28 mm in the Crowe II group, 0.12 ± 0.33 mm in the Crowe III group, and 0.14 ± 0.50 mm in the Crowe IV group (p = 0.572). In the Crowe IV group, the anterior superior iliac spine deviation was significantly lower using the “Matching with true and false acetabulum + iliac crest” method compared to the “Matching with true and false acetabulum” method (0.28 ± 0.49 mm vs. 3.29 ± 2.56 mm, p < 0.05). Conclusions: This study demonstrated the high accuracy of automatic AI-based segmentation, with a Dice Similarity Coefficient of 0.99 ± 0.01 and a Jaccard Index of 0.98 ± 0.02 in the combined cohort of Crowe type II, III, and IV cases (n = 30). The matching success rate was 100%, with additional points on the iliac crest, which improved matching accuracy and reduced deviations, depending on the case. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 4 2025 Subcutaneous and Periorbital Emphysema Following a Dental Procedure e83089 EN Takafumi Obara Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Kazuki Nakatsuji Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Hospital Takashi Hongo Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Tetsuya Yumoto Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Atsunori Nakao Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Subcutaneous emphysema following dental procedures is rare. We present the case of a young, healthy woman who was transferred from a dental clinic to our emergency department due to sudden swelling of the left orbit immediately after a dental procedure involving the use of the dental air and water syringe. The diagnosis of subcutaneous facial emphysema was made based on the patient's history, physical examination, and computed tomography imaging. The patient received prophylactic amoxicillin, and the lesion resolved completely in one week. Prompt clinical suspicion and a thorough evaluation of the signs and symptoms, including a detailed clinical history, are crucial for diagnosing subcutaneous emphysema following a dental procedure. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0916-9636 48 11 2025 Efficacy and safety of esaxerenone with and without sodium–glucose cotransporter-2 inhibitor use in hypertensive patients with type 2 diabetes mellitus: a pooled analysis of five clinical studies 2924 2937 EN Hirohiko Motoki Department of Cardiovascular Medicine, Shinshu University School of Medicine Koichiro Kuwahara Department of Cardiovascular Medicine, Shinshu University School of Medicine Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kazuomi Kario Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine Tomohiro Katsuya Katsuya Clinic Tatsuo Shimosawa Department of Clinical Laboratory, School of Medicine, International University of Health and Welfare Kenichi Tsujita Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Shoko Suzuki Data Intelligence Department, Daiichi Sankyo Co. Ltd. Tomohiro Suedomi Primary Medical Science Department, Daiichi Sankyo Co. Ltd. Takashi Taguchi Primary Medical Science Department, Daiichi Sankyo Co. Ltd. This pooled subanalysis of five multicenter, prospective, open-label, single-arm studies on esaxerenone aimed to evaluate the efficacy, organ-protective effects, and safety of esaxerenone in hypertensive patients with type 2 diabetes mellitus (T2DM), with and without concomitant sodium–glucose cotransporter-2 inhibitor (SGLT2i) therapy. In total, 283 and 279 patients were included in the safety (with SGLT2i, 148; without, 135) and full analysis sets (with SGLT2i; 145; without, 134), respectively. Significant changes in morning home systolic/diastolic blood pressure (SBP/DBP) from baseline to Week 12 were shown in the overall population (mean change: −11.9/−5.2 mmHg, both P < 0.001) and both SGLT2i and non-SGLT2i subgroups (−11.3/−4.8 and −12.5/−5.7 mmHg, respectively, all P < 0.001). Similar findings were observed in bedtime home and office SBP/DBP. The proportions of patients who achieved target home SBP/DBP < 135/85 mmHg were 71.2% (overall population) and 70.5% and 71.9% in the SGLT2i and non-SGLT2i subgroups, respectively. The urine albumin-to-creatinine ratio significantly improved from baseline to Week 12 in the overall population and SGLT2i subgroups (percentage change in geometric mean from baseline: −42.8%, −43.0%, and −42.6%, respectively, all P < 0.001). N-terminal pro-B-type natriuretic peptide levels improved in all groups. The incidence of serum potassium ≥5.5 mEq/L was 2.0% vs 5.2% in the SGLT2i vs non-SGLT2i subgroups. Esaxerenone demonstrated significant BP-lowering effects, and improved renal and cardiovascular parameters, regardless of SGLT2i use. Safety was consistent across groups, with the numerically lower incidence of serum potassium ≥5.5 mEq/L in the SGLT2i subgroup suggesting a potential mitigating effect of SGLT2is on the risk of hyperkalemia. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0916-9636 48 9 2025 Efficacy and safety of esaxerenone in hypertensive patients with chronic kidney disease, with or without type 2 diabetes mellitus: a pooled analysis of five clinical studies 2413 2426 EN Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hirohiko Motoki Department of Cardiovascular Medicine, Shinshu University School of Medicine Koichiro Kuwahara Department of Cardiovascular Medicine, Shinshu University School of Medicine Kazuomi Kario Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine Tomohiro Katsuya Katsuya Clinic Tatsuo Shimosawa Department of Clinical Laboratory, School of Medicine, International University of Health and Welfare Kenichi Tsujita Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Shoko Suzuki Data Intelligence Department, Daiichi Sankyo Co., Ltd. Tomohiro Suedomi Primary Medical Science Department, Daiichi Sankyo Co., Ltd. Takashi Taguchi Primary Medical Science Department, Daiichi Sankyo Co., Ltd. Effective management of blood pressure (BP) and albuminuria are crucial for suppressing chronic kidney disease (CKD) progression and cardiovascular risks in hypertension. This pooled analysis evaluated the antihypertensive effects, organ-protective effects, and safety of esaxerenone in hypertensive patients with CKD by integrating five clinical studies of esaxerenone. Patients were divided based on type 2 diabetes mellitus (T2DM) status (with or without T2DM) and creatinine-based estimated glomerular filtration rate (eGFRcreat) (30 to <60 and ≥60 mL/min/1.73 m2). Significant changes in morning home BP from baseline at Week 12 were observed in the overall population (mean change −12.8/ − 5.4 mmHg), T2DM subgroups ( − 12.2/ − 4.5 and −14.5/ − 7.8 mmHg), and eGFRcreat subgroups ( − 12.5/ − 4.7 and −14.0/ − 6.9 mmHg) (all P < 0.001). Bedtime home and office BP showed similar tendencies. Urine albumin-to-creatinine ratio significantly improved from baseline at Week 12 in the overall population (mean change: −55.2%), T2DM subgroups ( − 56.5% and −52.0%), and eGFRcreat subgroups ( − 54.6% and −55.4%) (all P < 0.001). N-terminal pro-B-type natriuretic peptide levels significantly decreased in the overall population (percent change: −14.1%) and subgroup without T2DM ( − 25.3%). The incidence of serum potassium ≥5.5 mEq/L was lower in the subgroup with T2DM vs without T2DM (3.1% and 11.3%), potentially related to the use of sodium–glucose cotransporter 2 inhibitors. These findings highlight the sustained BP-lowering effect of esaxerenone throughout the day in hypertensive patients with CKD, irrespective of T2DM status, and its significant reduction in albuminuria. The data support the safety and efficacy of esaxerenone in this patient population, underscoring its potential as a valuable therapeutic option. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 14 1 2024 Association between proteinuria and mineral metabolism disorders in chronic kidney disease: the Japan chronic kidney disease database extension (J-CKD-DB-Ex) 27481 EN Sho Shimamoto Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University Takako Nakahara Department of Medical Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare Shunsuke Yamada Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University Hajime Nagasu Department of Nephrology and Hypertension, Kawasaki Medical School Seiji Kishi Department of Nephrology and Hypertension, Kawasaki Medical School Naoki Nakashima Department of Medical Informatics, Graduate School of Medical Science, Kyushu University Kazuhiko Tsuruya Department of Nephrology, Nara Medical University Hirokazu Okada Department of Nephrology, Faculty of Medicine, Saitama Medical University Kouichi Tamura Department of Medical Science and Cardiorenal Medicine, Graduate School of Medicine, Yokohama City University Ichiei Narita Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences Shoichi Maruyama Department of Nephrology, Nagoya University Graduate School of Medicine Yuichiro Yano Department of General Medicine, Juntendo University Faculty of Medicine Takashi Yokoo Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine Takashi Wada Department of Nephrology and Rheumatology, Kanazawa University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Eiichiro Kanda Department of Health Data Science, Kawasaki Medical School Hiromi Kataoka Department of Medical Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare Masaomi Nangaku Division of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine Naoki Kashihara Department of Nephrology and Hypertension, Kawasaki Medical School Toshiaki Nakano Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University Chronic kidney disease-mineral and bone disorder (CKD-MBD) are recognized as a systemic disease affecting the prognosis of patients with CKD. Proper management of CKD-MBD is important to improve the prognosis of patients with CKD. Although proteinuria is recognized as a poor prognostic factor in these patients, few reports have examined its association with CKD-MBD. We examined the association between proteinuria and CKD-MBD using data from the Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex). Among the patients registered in the J-CKD-DB-Ex, 30,977 with CKD stages G2–G5 who had serum creatinine, albumin, calcium, and phosphate concentrations measured at least once and urinalysis performed were included. The patients were divided into four groups (negative, 1+, 2+, and 3+) according to the degree of proteinuria. The association between proteinuria and CKD-MBD was examined by a logistic regression analysis. In a model adjusted for age, sex, diabetes, and the estimated glomerular filtration rate (eGFR), the odds ratio of the 3 + group compared with the negative group significantly increased to 2.67 (95% confidence interval, 2.29–3.13) for hyperphosphatemia, 2.68 (1.94–3.71) for hypocalcemia, and 1.56 (1.24–1.98) for hypomagnesemia. Proteinuria is associated with hyperphosphatemia, hypocalcemia, and hypomagnesemia in patients with CKD independently of eGFR. No potential conflict of interest relevant to this article was reported.

Japan Medical Association Acta Medica Okayama 2433-3298 8 2 2025 Successful Transplantation of Multiple Organs from Donor after Helium Asphyxiation: First Case Report in Japan 650 653 EN Shunta Jinno Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Helium inhalation has increased, but most cases are either minor injuries or deaths; there have not yet been any reported cases of brain death leading to organ donation. We report a patient who attempted helium inhalation and was declared brain dead and became an organ donor without complications. To the best of our knowledge, this is the first reported case of deceased organ donation following helium asphyxiation in Japan. The patient in cardiac arrest was found with a helium-filled vinyl bag sealed around the neck. During emergency medical transport to the hospital, a spontaneous return of circulation was obtained after 31 minutes of cardiopulmonary resuscitation. Upon hospital arrival, the physical examination revealed dilated pupils with no response to light. Electrocardiography showed widespread ST-segment depression and ST-segment elevation in augmented Vector Right, as well as elevated cardiac enzymes and decreased myocardial contractility. Head computed tomography revealed diffuse cerebral edema and loss of the gray-white matter boundary without signs of air embolism in the cerebral and coronary arteries. Despite comprehensive post-cardiac arrest care with recovery of organ function, brain death was confirmed on day 4 after hospitalization. The family consented to organ donation on the 11th day of hospitalization. The heart, lungs, liver, and two kidneys were successfully transplanted and all organs functioned. All organ grafts were functioning well at the 3-month follow-up. Our case demonstrates that brain death caused by helium inhalation is not a contraindication to organ donation. No potential conflict of interest relevant to this article was reported.

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

Bioscientifica Acta Medica Okayama 2052-0573 2025 1 2025 Adult hypophosphatasia presenting with recurrent acute joint pain e240121 EN Hayao Yoshida Department of Diabetes and Endocrinology, Shiga General Hospital Takaaki Murakami Department of Diabetes and Endocrinology, Shiga General Hospital Atsubumi Ogawa Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine Takashi Sunouchi Division of Nephrology and Endocrinology, The University of Tokyo Hospital Naoko Hidaka Division of Nephrology and Endocrinology, The University of Tokyo Hospital Nobuaki Ito Osteoporosis Center, The University of Tokyo Hospital Hiromi Murakami Department of Genomic Medicine, Kyoto University Graduate School of Medicine Hidenori Kawasaki Department of Genomic Medicine, Kyoto University Graduate School of Medicine Tomoyuki Akiyama Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsumi Nakajima Department of Diabetes and Endocrinology, Shiga General Hospital Daisuke Yabe Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine Taizo Yamamoto Department of Diabetes and Endocrinology, Shiga General Hospital Hypophosphatasia (HPP) is a genetic disorder due to pathological variants in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (ALP). HPP is typically associated with bone-related symptoms, such as bone deformity, fractures and bone pain in children, but can appear in adults with symptoms resembling arthritis. A 22-year-old male experienced repeated and severe sudden attacks of joint pain in the elbows and knees. Magnetic resonance imaging and joint ultrasonography showed joint effusions indicating chronic inflammation. Blood biochemical tests revealed a remarkably low serum ALP level, and repeated examination confirmed a sustained low ALP level; urine phosphoethanolamine, plasma inorganic pyrophosphate and plasma pyridoxal-5′-phosphate levels were elevated, raising concern for HPP. While the patient had no history of premature loss of primary teeth, fragility fractures, muscle weakness or abnormalities in growth, genetic testing revealed a likely pathogenic and a pathogenic heterozygous variant in the ALPL gene, i.e., c.979T>C (p.Phe327Leu) and c.1559del (p.Leu520Argfs), confirming HPP. Additional genetic testing of his parents showed a heterozygous c.1559del variant in his father and a heterozygous c.979T>C variant in his mother. A diagnosis of adult HPP due to compound heterozygous mutations was therefore confirmed. Enzyme replacement therapy with asfotase alfa was then introduced; no attacks of arthralgia occurred in the 1-year period since then. This case highlights the possibility of HPP in adults who present clinically with repeated joint symptoms and low serum ALP levels but without bone-related symptoms. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 0300-9572 215 2025 Compression only CPR and mortality in pediatric out-of-hospital cardiac arrest during COVID-19 pandemic 110706 EN Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background: The COVID-19 pandemic influenced resuscitation practices worldwide, leading to a notable decline in rescue breathing cardiopulmonary resuscitation (RB-CPR), even in pediatric out-of-hospital cardiac arrest (OHCA). Understanding the impact of this decline is important to assess the role of rescue breathing in pediatric resuscitation. This study aimed to evaluate the impact of the reduced RB-CPR during the COVID-19 pandemic on mortality and neurological outcomes among pediatric OHCA patients in Japan.<br> Methods: This retrospective cohort study utilized data from the nationwide All-Japan Utstein Registry for pediatric OHCA patients (≤17 years) who received bystander CPR between January 2017 and December 2021. Data were compared in pre-COVID-19 (2017–2019) versus pandemic (2020–2021) periods. Bystander CPR were classified as RB-CPR or chest compression-only CPR (CO-CPR). The primary outcome was 30-day mortality, with secondary outcomes including the absence of return of spontaneous circulation and unfavorable neurological outcomes (Cerebral Performance Category scores of 3–5). Adjusted risk ratios (aRR) with 95 % confidence intervals (CI) were estimated using Poisson regression.<br> Results: Of 7,162 pediatric OHCA cases, 3,352 (46.8 %) received bystander CPR. RB-CPR decreased from 33.0 % pre-pandemic to 21.1 % during the pandemic. CO-CPR was associated with higher 30-day mortality (aRR: 1.16; 95 % CI: 1.08–1.24) and unfavorable neurological outcomes (aRR: 1.10; 95 % CI: 1.05–1.16). These trends were consistent across age groups and arrest etiologies, particularly for non-cardiac causes. More significantly, the decrease in RB-CPR was estimated to contribute to 10.7 excess deaths annually during the pandemic.<br> Conclusions: The findings highlight the importance of rescue breathing in pediatric OHCA. CO-CPR, while suitable for adults, may compromise outcomes in children. Emphasizing rescue breathing in pediatric resuscitation training and integrating infection control measures is essential for future public health emergencies. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2666-5204 25 2025 Mid-term (30- to 90-day) neurological changes in out-of-hospital cardiac arrest survivors receiving extracorporeal cardiopulmonary resuscitation: a nationwide retrospective study (the JAAM-OHCA registry) 101057 EN Takashi Hongo Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Tetsuya Yumoto Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Tsuyoshi Nojima Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Takafumi Obara Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Yoshiyuki Ueda Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Takashi Yorifuji Okayama University, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Epidemiology Atsunori Nakao Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Hiromichi Naito Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Background: Few studies have examined mid-term neurological changes in out-of-hospital cardiac arrest (OHCA) patients after receiving extracorporeal cardiopulmonary resuscitation (ECPR). This study aimed to evaluate neurological improvements between 30 and 90 days in OHCA patients treated with ECPR or conventional cardiopulmonary resuscitation (CCPR) using a large nationwide cohort.<br> Methods: This retrospective multicenter study used data from a Japanese nationwide OHCA registry. Participants were categorized into ECPR and CCPR groups based on the initial resuscitation method. Neurological changes between 30 and 90 days were assessed using Cerebral Performance Category (CPC) scores. The primary outcome was neurological improvement, defined as an improvement in CPC score during this period.<br> Results: A total of 4467 OHCA survivors at 30 days were included, 669 in the ECPR group and 3798 in the CCPR group. At 30 days, favorable neurological outcomes were observed in 318 ECPR patients (47.5 %) and 2103 CCPR patients (55.4 %). Neurological improvement between 30 and 90 days was more frequent in the ECPR group (83 [12.4 %] vs. 258 [6.7 %]). There was no significant difference in 90-day mortality between the two groups (82 [12.2 %] vs. 519 [13.6 %]). ECPR was independently associated with 30- to 90-day neurological improvement (adjusted odds ratio (OR) 2.01; 95 % confidence interval (CI), 1.38–2.93) but was not associated with 90-day mortality (adjusted OR 1.11; 95 % CI, 0.77–1.59).<br> Conclusion: ECPR was associated with a greater likelihood of neurological improvement between 30 and 90 days. By 90 days, mortality was nearly the same in both groups. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2044-6055 15 8 2025 Neurological outcomes with hypothermia versus normothermia in patients with moderate initial illness severity following resuscitation from out-of-hospital cardiac arrest: protocol for a multicentre randomised controlled trial (R-CAST OHCA) e101809 EN Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Mitsuaki Nishikimi Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Yohei Okada Department of Preventive Services, School of Public Health, Graduate School of Medicine, Kyoto University Hiroki Maeyama Department of Emergency and Critical Care Medicine, Tsuyama Chuo Hospital Takeyuki Kiguchi Division of Trauma and Surgical Critical Care, Osaka General Medical Center Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Kazuki Nishida Department of Biostatistics, School of Public Health, Graduate School of Medicine, Kyoto University Shigeyuki Matsui Department of Biostatistics, School of Public Health, Graduate School of Medicine, Kyoto University Yasuhiro Kuroda Emergency and Critical Care Center, TMG Asaka Medical Center Kei Nishiyama Division of Emergency and Critical Care Medicine, Niigata University Graduate School of Medical and Dental Science Taku Iwami Department of Preventive Services, School of Public Health, Graduate School of Medicine, Kyoto University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences JAAM R-CAST OHCA Trial Group Introduction Temperature control is a fundamental intervention for neuroprotection following resuscitation from cardiac arrest. However, evidence regarding the efficacy of hypothermia in post-cardiac arrest syndrome (PCAS) remains unclear. Retrospective studies suggest that the clinical effectiveness of hypothermia may depend on the severity of PCAS. The R-CAST OHCA trial aims to compare the efficacy of hypothermia versus normothermia in improving 30-day neurological outcomes in patients with moderately severe PCAS following out-of-hospital cardiac arrest.<br> Methods and analysis The multicentre, single-blind, parallel-group, superiority, randomised controlled trial (RCT) is conducted with the participation of 35 emergency and critical care centres and/or intensive care units at academic and non-academic hospitals. The study enrols moderately severe PCAS patients, defined as those with a revised post-Cardiac Arrest Syndrome for induced Therapeutic Hypothermia score of 5.5–15.5. A target number of 380 participants will be enrolled. Participants are randomised to undergo either hypothermia or normothermia within 3 hours after return of spontaneous circulation. Patients in the hypothermia group are cooled and maintained at 34°C until 28 hours post-randomisation, followed by rewarming to 37°C at a rate of 0.25°C/hour. Patients in the normothermia group are maintained at normothermia (36.5°C–37.7°C). Total periods of intervention, including the cooling, maintenance and rewarming phases, will occur 40 hours after randomisation. Other treatments for PCAS can be determined by the treating physicians. The primary outcome is a favourable neurological outcome, defined as Cerebral Performance Category 1 or 2 at 30 days after randomisation and compared using an intention-to-treat analysis.<br> Ethics and dissemination This study has been approved by the Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital, Ethics Committee (approval number: R2201-001). Written informed consent is obtained from all participants or their authorised surrogates. Results will be disseminated via publications and presentations.<br> Trial registration number jRCT1062220035. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 2666-6677 23 2025 AHA’s Life’s Essential-8 cardiovascular health metrics and progression of coronary artery calcification in Japanese men 101081 EN Rajib Mondal Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science Aya Kadota Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science Yuichiro Yano Department of General Medicine, Faculty of Medicine, Juntendo University Sayaka Kadowaki Department of Public Health, Shiga University of Medical Science Sayuki Torii Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science Keiko Kondo Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science Akiko Harada Department of Medical Statistics, NCD Epidemiology Research Center, Shiga University of Medical Science Megumi Kawashima Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science Itsuko Miyazawa Department of Internal Medicine, Shiga University of Medical Science Hiroyoshi Segawa NCD Epidemiology Research Center, Shiga University of Medical Science Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiyuki Watanabe Department of Radiology, Shiga University of Medical Science Yoshihisa Nakagawa Department of Cardiovascular Medicine, Shiga University of Medical Science Akira Fujiyoshi Department of Hygiene, School of Medicine, Okayama Medical University Katsuyuki Miura Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science Background and aims: The American Heart Association’s Life’s Essential-8 (LE8) cardiovascular health (CVH) metrics is considered a comprehensive framework for optimal cardiovascular wellbeing. However, its relationship with the progression of subclinical atherosclerosis, like coronary artery calcification (CAC), is not clarified. We investigated the associations of LE8 CVH metrics with the prevalence and progression of CAC in Japanese men.<br> Methods: We analyzed data from 760 asymptomatic men participating in the Shiga Epidemiological Study of Subclinical Atherosclerosis. We assessed baseline (2006–2008) LE8 CVH (low, 0–49 points; moderate, 50–79 points; high, 80–100 points) using its eight components (diet, physical activity assessed by step count, smoking, sleep, body mass index, blood lipids, blood glucose, blood pressure). We quantified CAC at baseline and follow-up of 5 years employing Agatston’s method and defined its baseline prevalence (CAC >0) and progression (employing Berry’s criteria). Modified Poisson regression analyses were used to estimate risk ratio (RR) and 95 % confidence interval (CI), adjusted for age and family history of cardiovascular disease.<br> Results: Participants (mean [SD] age, 63.8 [9.4] years) had 63.2 % and 44.9 % prevalence of CAC at baseline and CAC progression at follow-up, respectively. Individuals with moderate and low CVH at baseline had a higher risk of prevalent CAC (RR [95 % CI], 1.42 [1.18–1.71] and 2.07 [1.67–2.57], respectively) at baseline, compared to those with high CVH. Those with moderate and low CVH at baseline had a higher risk of CAC progression (RR [95 % CI], 1.52 [1.17–1.97] and 1.99 [1.42–2.81], respectively), compared to high CVH individuals.<br> Conclusions: A lower LE8 CVH is significantly associated with a higher risk of prevalence and progression of CAC in general Japanese men. No potential conflict of interest relevant to this article was reported.

Public Library of Science (PLoS) Acta Medica Okayama 1932-6203 20 10 2025 Relationship between obesity indices and cognitive function in Japanese men: A cross-sectional study e0332595 EN Satoshi Matsuno Department of Psychiatry, Shiga University of Medical Science Yuji Ozeki Department of Psychiatry, Shiga University of Medical Science Sayaka Kadowaki NCD Epidemiology Research Center, Shiga University of Medical Science Sayuki Torii NCD Epidemiology Research Center, Shiga University of Medical Science Keiko Kondo NCD Epidemiology Research Center, Shiga University of Medical Science Naoko Miyagawa Department of Preventive Medicine and Public Health, Keio University School of Medicine Azusa Shima Department of Clinical Nursing, Shiga University of Medical Science Mizuki Ohashi NCD Epidemiology Research Center, Shiga University of Medical Science Itsuko Miyazawa Department of Medicine, Shiga University of Medical Science Hiroyoshi Segawa NCD Epidemiology Research Center, Shiga University of Medical Science Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Aya Kadota NCD Epidemiology Research Center, Shiga University of Medical Science Katsuyuki Miura NCD Epidemiology Research Center, Shiga University of Medical Science We aimed to investigate the associations among various obesity indices, including visceral (VAT) and subcutaneous adipose tissue (SAT), and cognitive function in community-dwelling Japanese men. This population-based cross-sectional study used data of 853 men who participated in the follow-up examinations of the Shiga Epidemiological Study of Subclinical Atherosclerosis. Among them, we analyzed data of 776 men who completed the Cognitive Abilities Screening Instrument (CASI) and had abdominal VAT and SAT areas measured using computed tomography. The VAT-to-SAT ratio (VSR) was calculated; participants were categorized into VSR quartiles. Using analysis of covariance, we computed crude and adjusted means of the CASI total and domain scores across VSR quartiles, adjusting for potential confounders. No significant differences were observed in total CASI scores among body mass index, VAT, or SAT quartiles. However, in the multivariable-adjusted model, participants in the lowest VSR quartile (Q1) had significantly lower CASI total scores than those in the third quartile (Q3) (Q1: 89.5, Q3: 90.9). Low VSR was independently associated with lower cognitive function in a community-based sample of middle-aged and older Japanese men. In summary, VSR may be associated with cognitive function in Japanese men, highlighting the importance of fat distribution in cognitive health and highlighting VSR as a useful indicator. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 14 17 2025 Potential of Kidney Exchange Programs (KEPs) in Japan for Donor-Specific Antibody-Positive Kidney Transplants: A Questionnaire Survey on KEPs and a Multi-Institutional Study Conducting Virtual Cross-Matching Simulations 6122 EN Taihei Ito Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University Miki Ito Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University Naohiro Aida Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University Kei Kurihara Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University Akihiro Terao Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University Yoshihiko Watarai Department of Transplant Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital Mitsuru Saito Division of Blood Purification, Akita University Hospital Keizo Kaku Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University Daisuke Ishii Department of Urology, Kitasato University of Medicine Satoshi Sekiguchi Transplantation Surgery, Japan Community Healthcare Organization Sendai Hospital Tatsuo Yoneda Unit of Dialysis, Department of Urology, Nara Medical University Kohei Unagami Organ Transplant Medicine, Tokyo Women’s Medical University Masayuki Tasaki Division of Urology, Department of Regenerative & Transplant Medicine, Graduate School of Medical and Dental Sciences, Niigata University Hitoshi Iwamoto Department of Kidney Transplantation Surgery, Tokyo Medical University Hachioji Medical Center Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Takahashi Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of Tsukuba Kazuaki Yamanaka Department of Urology, Osaka University Graduate School of Medicine Mikio Sugimoto Department of Urology, Faculty of Medicine, Adrenal Surgery and Renal Transplantation, Kagawa University Kouhei Nishikawa Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine Chikashi Seto Department of Urology, Toyama Prefectural Central Hospital Masaki Muramatsu Department of Nephrology, Toho University Faculty of Medicine Toshihiro Asai Department of Kidney Transplant and Dialysis, Osaka City General Hospital Daiki Iwami Division of Renal Surgery and Transplantation, Department of Urology, Jichi Medical University Yasutoshi Yamada Department of Blood Purification, Kagoshima University Hospital Shigeyoshi Yamanaga Department of Transplant Surgery, Japanese Red Cross Kumamoto Hospital Tomonori Komatsu Department of Urology, Chukyo Hospital, Japan Community Healthcare Organization Masayoshi Miura Department of Renal Transplantation Surgery and Urology, Sapporo Hokuyu Hospital Takahiro Nohara Department of Urology, Kanazawa University Hospital Michihiro Maruyama Department of Frontier Surgery, Chiba University School of Medicine Yuki Miyauchi Department of Urology, Ehime University Toshiaki Tanaka Department of Urology, Sapporo Medical University Michio Nakamura Department of Transplant Surgery, Tokai University School of Medicine Kiyohiko Hotta Department of Renal and Genitourinary Surgery, Faculty of Medicine, Hokkaido University Takashi Kenmochi Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University Objectives: To clarify the need for a kidney exchange program (KEP) in Japan by conducting a questionnaire survey on KEPs and simulated KEPs by virtual cross-matching based on past cases of transplantation avoidance. Methods: In addition to the content regarding KEPs, an electronic survey was conducted to investigate the number of cases of kidney transplant abandonment due to “immunological” reasons over the past 10 years (2012–2021). Virtual cross-matching was conducted to simulate the feasibility of avoiding immunological risks and enabling kidney transplantation in patients who were previously unable to undergo the procedure. Results: The survey received responses from 107 facilities (response rate: 81.7%). In response to the question about the necessity of a KEP in Japan, 71 facilities (66.4%) indicated that KEPs are necessary. In addition, 251 living-donor kidney transplants were abandoned for “immunological” reasons over the past decade (2012–2021). Among the 80 pairs for which detailed information was available, virtual cross-matching simulations showed that 37/80 pairs (46.3%) were donor-specific antibody (DSA)-negative for blood type-matched combinations, and 41/80 pairs (51.3%) were DSA-negative for blood type-incompatible transplants. Conclusions: The need for a KEP in Japan and its potential usefulness were demonstrated. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 The significance of adding posterior decompression to spine stabilization in metastatic spinal surgery: a multicenter prospective study 27684 EN Hiroyuki Tominaga Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Ichiro Kawamura Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Hirofumi Shimada Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Hiromi Sasaki Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Noboru Taniguchi Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Yuki Shiratani Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University Akinobu Suzuki Department of Orthopaedic Surgery, Osaka Metropolitan University Hidetomi Terai Department of Orthopaedic Surgery, Osaka Metropolitan University Takaki Shimizu Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University Kenichiro Kakutani Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Yutaro Kanda Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Masayuki Ishihara Department of Orthopaedic Surgery, Kansai Medical University Hospital Masaaki Paku Department of Orthopaedic Surgery, Kansai Medical University Hospital Yohei Takahashi Department of Orthopaedic Surgery, Keio University Toru Funayama Department of Orthopaedic Surgery, Institute of Medicine, University of Tsukuba Kousei Miura Department of Orthopaedic Surgery, Institute of Medicine, University of Tsukuba Eiki Shirasawa Department of Orthopaedic Surgery, Kitasato University School of Medicine Hirokazu Inoue Rehabilitation Center, Jichi Medical University Hospital Atsushi Kimura Department of Orthopaedics, Jichi Medical University Takuya Iimura Department of Orthopaedic Surgery, Dokkyo Medical University Hiroshi Moridaira Department of Orthopaedic Surgery, Dokkyo Medical University Hideaki Nakajima Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui Shuji Watanabe Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui Koji Akeda Department of Orthopaedic Surgery, Mie University Graduate School of Medicine Norihiko Takegami Department of Orthopaedic Surgery, Mie University Graduate School of Medicine Kazuo Nakanishi Department of Orthopaedic Surgery, Kawasaki Medical School Hirokatsu Sawada Department of Orthopaedic Surgery, Nihon University School of Medicine Koji Matsumoto Department of Orthopaedic Surgery, Nihon University School of Medicine Masahiro Funaba Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine Hidenori Suzuki Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine Haruki Funao Department of Orthopaedic Surgery, International University of Health and Welfare Narita Hospital Tsutomu Oshigiri Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine Takashi Hirai Department of Orthopedic Surgery, Institute of Science Tokyo Bungo Otsuki Department of Orthopaedic Surgery, Kyoto University Hospital Kazu Kobayakawa Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University Koji Uotani Department of Orthopaedic Surgery, Okayama University Hospital Hiroaki Manabe Department of Orthopedics, Tokushima University Shinji Tanishima Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University Ko Hashimoto Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine Chizuo Iwai Department of Orthopaedic Surgery, Gifu University Hospital Daisuke Yamabe Department of Orthopaedic Surgery, Iwate Medical University Akihiko Hiyama Department of Orthopaedic Surgery, Tokai University School of Medicine Shoji Seki Department of Orthopaedic Surgery, University of Toyama Yuta Goto Department of Orthopaedic Surgery, Nagoya City University Masashi Miyazaki Department of Orthopaedic Surgery, Faculty of Medicine, Oita University Kazuyuki Watanabe Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine Toshio Nakamae Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Takashi Kaito Department of Orthopedic Surgery, Osaka University Graduate School of Medicine Hiroaki Nakashima Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Narihito Nagoshi Department of Orthopaedic Surgery, Keio University Satoshi Kato Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University Shiro Imagama Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Kota Watanabe Department of Orthopaedic Surgery, Keio University Gen Inoue Department of Orthopaedic Surgery, Kitasato University School of Medicine Takeo Furuya Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University The usefulness of spine stabilization for treating metastatic spinal tumors with tumor-induced instability has been reported. However, no reports have prospectively evaluated the effectiveness of adding posterior decompression to stabilization surgery for improving symptoms. This multicenter prospective study aimed to determine whether adding posterior decompression to spine stabilization surgery for metastatic spinal tumors affects postoperative outcomes and complications. A total of 263 patients who underwent spine stabilization with (n = 189) or without (n = 74) decompression were analyzed. Patient demographics, the Spinal Instability Neoplastic Score (SINS), and the Epidural Spinal Cord Compression (ESCC) score were recorded. The outcomes were assessed preoperatively and at 1 and 6 months postoperatively in terms of neurological status, the Barthel Index, the EQ-5D-5 L, and the visual analog scale (VAS). Decompression was primarily performed in patients with severe neurological deficits and high-grade ESCC. Both groups showed postoperative improvement. Propensity score matching was applied to adjust for baseline differences. After matching, there were no significant differences in functional improvement between the decompression and nondecompression groups, and the complication rates were comparable. In matched patients presenting primarily with spinal instability and pain, the addition of decompression did not appear to confer a significant functional benefit within 6 months postoperatively. No potential conflict of interest relevant to this article was reported.

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

American Geophysical Union (AGU) Acta Medica Okayama 2169-9313 130 10 2025 Electrical Conductivity of Carbonated Hydrous Basaltic Melt: Implications for the Conductivity Anomaly Beneath the Ocean Floors e2025JB032215 EN Bin Zhao Institute for Planetary Materials, Okayama University Jintao Zhu Institute for Planetary Materials, Okayama University Jinze He Institute for Planetary Materials, Okayama University Takashi Yoshino Institute for Planetary Materials, Okayama University We measured the electrical conductivity of CO2 and H2O-bearing basaltic melts up to 1750 K at 2 GPa, corresponding to pressure around the lithosphere-asthenosphere boundary. The electrical conductivity of the dry and hydrous samples is comparable to those reported by previous studies on the Fe-free basaltic melt. The substantial CO2 can limit the water solubility in basaltic melt at 2 GPa. Both CO2 and H2O, which cannot completely dissolve in the melt, coexist as fluid phases, resulting in reduced electrical conductivity of the basaltic melt, which has a lower water content relative to the amount of volatile components in the bulk starting system. The activation enthalpy of basaltic melt is markedly higher than those of more evolved silicate melts, especially on the H2O-poor condition, due to the more enriched alkaline earth elements. The present results suggest that an overall melt fraction of 0.1–5.3 vol% is needed to account for the high electrical conductivity anomalies (10−1.3 to 10−0.3 S/m) beneath the oceanic plate near the East Pacific Rise and Cocos plate. However, for those regions where the electrical conductivity is extremely high (≥10−0.3 S/m), more than 6 wt% H2O is expected to incorporate to maintain a melt fraction that will not trigger mechanical instability. In turn, it requires a low CO2 budget or degree of carbonation within these regions. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 2376-7839 11 5 2025 Vanishing White Matter Disease With EIF2B2 c.254T >A Variant e200293 EN Toshiyuki Kakumoto Department of Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Ryo Tokimura Department of Neurology, Graduate School of Medicine, The University of Tokyo Yoko Tsuboyama Department of Neurology, Graduate School of Medicine, The University of Tokyo Yasufumi Hayashi Department of Neurology, Graduate School of Medicine, The University of Tokyo Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo Atsushi Iwata Department of Neurology, Graduate School of Medicine, The University of Tokyo Meiko Hashimoto Maeda Department of Neurology, Graduate School of Medicine, The University of Tokyo Jun Shimizu Department of Neurology, Graduate School of Medicine, The University of Tokyo Wataru Gonoi Department of Radiology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Mitsui Department of Neurology, Graduate School of Medicine, The University of Tokyo Shoji Tsuji Department of Molecular Neurology, Graduate School of Medicine, The University of Tokyo Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Objectives<br> Typical MRI findings of vanishing white matter disease (VWM) include diffuse white matter lesions with cystic degeneration. However, mild cases may lack these typical features, posing diagnostic challenges.<br> Methods<br> We describe 2 of 3 individuals carrying the homozygous c.254T >A variant in EIF2B2 identified at our hospital, excluding 1 previously reported case.1 Genetic analyses were performed using whole-genome sequence or whole-exome sequence analysis, and detected variants were confirmed by direct nucleotide sequence analysis. Brain MRI findings and clinical features were reviewed for the 2 individuals along with other cases in the literature with the same variant.<br> Results<br> A 69-year-old woman presented with recurrent transient dizziness and secondary amenorrhea. MRI of the brain revealed small T2-hyperintense lesions confined to the subcortical white matter with hyperintensities on diffusion-weighted images and mildly elevated apparent diffusion coefficient values. A 28-year-old woman presented with transient dizziness and secondary amenorrhea. MRI of the brain showed mild T2-hyperintense lesions in the cerebral white matter with frontal predominance.<br> Discussion<br> This report highlights the clinically mild cases of VWM with subtle abnormalities on brain MRI who had the homozygous c.254T >A in EIF2B2, further expanding the clinical spectrum of VWM and underscoring the importance of genetic assessments in the diagnosis of individuals with mild clinical and MRI findings. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0022-510X 478 2025 Two Japanese families with adult-onset leukoencephalopathy caused by pathogenic variants in CST3 123708 EN Kenta Orimo Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Kazutaka Shiomi Division of Respirology, Rheumatology, Infectious Diseases, and Neurology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki Ryoji Goto Department of Neurology, Graduate School of Medicine, The University of Tokyo Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo Yumiko Kuromi Department of Neurology, Fukushima Medical University Nozomu Matsuda Department of Neurology, Fukushima Medical University Kazuaki Kanai Department of Neurology, Fukushima Medical University Ryo Kurokawa Department of Radiology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Mitsui Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Junko Nomoto Institute of Medical Genomics, International University of Health and Welfare Masaki Tanaka Institute of Medical Genomics, International University of Health and Welfare Yosuke Omae Genome Medical Science Project, National Institute of Global Health and Medicine Yosuke Kawai Genome Medical Science Project, National Institute of Global Health and Medicine Katsushi Tokunaga Genome Medical Science Project, National Institute of Global Health and Medicine Shoji Tsuji Department of Neurology, Graduate School of Medicine, The University of Tokyo Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo CST3 (NM_000099.4) encodes cystatin C, whose C-terminal truncating variants in this gene have recently been reported to cause adult-onset leukoencephalopathy, characterized by headaches, transient neurological symptoms, and distinct imaging findings. We present four patients from two Japanese families, including one with a novel variant (c.358-2_395del). Three patients from one family developed chronic headaches around the age of 20, whereas the patient from the other family remained asymptomatic until his fifties. mRNA analysis of the patient with c.358-2_395del revealed a splicing alteration leading to an in-frame deletion (p.Lys120_Gln133del), representing the first CST3 variant that does not result in a truncated protein. These findings broaden our understanding of the clinical and genetic spectra of CST3-related leukoencephalopathy (114 words). No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Blood Pressure and Heart Rate Patterns Identified by Unsupervised Machine Learning and Their Associations with Subclinical Cerebral and Renal Damage in a Japanese Community: The Masuda Study 369 379 EN Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Minako Kinuta Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sosuke Munetomo Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mari Fukuda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuhide Kojima Department of Radiology, Okayama University Hospital Kaori Taniguchi Department of Environmental Medicine and Public Health, Izumo, Shimane University Faculty of Medicine Noriko Nakahata Department of Health and Nutrition, The University of Shimane Faculty of Nursing and Nutrition Hideyuki Kanda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/69438 We applied unsupervised machine learning to analyze blood pressure (BP) and resting heart rate (HR) patterns measured during a 1-year period to assess their cross-sectional relationships with subclinical cerebral and renal target damage. Dimension reduction via uniform manifold approximation and projection, followed by K-means++ clustering, was used to categorize 362 community-dwelling participants (mean age, 56.2 years; 54.9% women) into three groups: Low BP and Low HR (Lo-BP/Lo-HR), High BP and High HR (Hi-BP/Hi-HR), and Low BP and High HR (Lo-BP/Hi-HR). Cerebral vessel lesions were defined as the presence of at least one of the following magnetic resonance imaging findings: lacunar infarcts, white matter hyperintensities, cerebral microbleeds, or intracranial artery stenosis. A high urinary albumin-to-creatinine ratio (UACR) was defined as the top 10% (≥ 12 mg/g) of the mean value from ≥2 measurements. Poisson regression with robust error variance, adjusted for demographics, lifestyle, and medical history, showed that the Hi-BP/Hi-HR group had relative risks of 3.62 (95% confidence interval, 1.75-7.46) for cerebral vessel lesions and 3.58 (1.33-9.67) for high UACR, and the Lo-BP/Hi-HR group had a relative risk of 3.09 (1.12-8.57) for high UACR, compared with the Lo-BP/Lo-HR group. These findings demonstrate the utility of an unsupervised, data-driven approach for identifying physiological patterns associated with subclinical target organ damage. 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 Periodontitis associated with Porphyromonas gingivalis infection is a risk factor for infertility through uterine hypertrophy 34964 EN Chiaki Kamei-Nagata Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Omori Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidefumi Sako Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Kyosuke Sakaida Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Masa-aki Nakayama Department of Oral Microbiology, Faculty 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 Hiroki Mandai Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science Moyuka Kubota-Takamori Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumiko Kiyama Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayuki Ishii Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kimito Hirai Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsushi Ikeda Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Kazu Takeuchi-Hatanaka Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Yuki Shinoda-Ito Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masako Tai-Tokuzen Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Ai Sakamoto Center for Reproductive Medicine, Miyake Clinic Machiko Kiyokawa Center for Reproductive Medicine, Miyake Clinic Tomomi Yamanishi Center for Reproductive Medicine, Miyake Clinic Takashi Oda Center for Reproductive Medicine, Miyake Clinic Masayuki Takigawa Miyake Hello Dental Clinic, Pediatric Dentistry and Orthodontics Tadashi Yamamoto The Center for Graduate Medical Education (Dental Division), Okayama University Hospital Takahito Miyake Center for Reproductive Medicine, Miyake Clinic Shogo Takashiba Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Periodontitis has recently been recognized as a potential risk factor for infertility due to its adverse effect on conception, although the underlying mechanisms remain unclear. This study investigated serum IgG antibody titers against periodontopathogenic bacteria in women with unexplained infertility and investigated how periodontal inflammation affects pregnancy and uterine function using a ligature-induced periodontitis mouse model infected with Porphyromonas gingivalis (Pg). IgG antibody titers against seven periodontopathogenic bacteria strains were measured by ELISA in 76 spontaneously pregnant women and 70 women undergoing infertility treatment. In the in vivo study, periodontitis mice were bred four weeks after periodontitis induction. Birth numbers, newborn weights, and gestation periods were assessed. To evaluate periodontal inflammation, alveolar bone, serum, and uterus was collected before mating. Uterine tissue was evaluated through histological and immunohistochemical staining. Women receiving infertility treatment were significantly older and had higher IgG titers against three Pg strains. Periodontitis mice had fewer births, lower newborn weights, and increased uterine cross-sectional areas. Additionally, elevated estrogen receptor α and progesterone receptor expression levels were observed in endometrial and stromal tissues. These results suggest that periodontitis may cause uterine hypertrophy and hormone receptor changes, potentially impairing pregnancy. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1342-1751 29 5 2025 Development and validation of an algorithm for identifying patients undergoing dialysis from patients with advanced chronic kidney disease 650 661 EN Takahiro Imaizumi Department of Nephrology, Nagoya University Graduate School of Medicine Takashi Yokota Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital Kouta Funakoshi Kyusyu University Hospital Kazushi Yasuda Department of Nephrology, Nagoya University Graduate School of Medicine Akiko Hattori Department of Nephrology, Nagoya University Graduate School of Medicine Akemi Morohashi Department of Advanced Medicine, Nagoya University Hospital Tatsumi Kusakabe Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital Masumi Shojima Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University Sayoko Nagamine Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University Toshiaki Nakano Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University Yong Huang Division of Medical Informatics, Okayama University Hospital Hiroshi Morinaga Department of Comprehensive Therapy for Chronic Kidney Disease, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miki Ohta Clinical Research Promotion Center, The University of Tokyo Hospital Satomi Nagashima Department of Healthcare Information Management, The University of Tokyo Hospital Ryusuke Inoue Medical Information Technology Center, Tohoku University Hospital Naoki Nakamura Medical Information Technology Center, Tohoku University Hospital Hideki Ota Medical Information Technology Center, Tohoku University Hospital Tatsuya Maruyama Clinical Research Promotion Center, The University of Tokyo Hospital Hideo Gobara Division of Medical Informatics, Okayama University Hospital Akira Endoh Department of Medical Informatics, Hokkaido University Hospital Masahiko Ando Department of Nephrology, Nagoya University Graduate School of Medicine Yoshimune Shiratori Medical IT Center, Nagoya University Hospital Shoichi Maruyama Department of Nephrology, Nagoya University Graduate School of Medicine Background Identifying patients on dialysis among those with an estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2 remains challenging. To facilitate clinical research in advanced chronic kidney disease (CKD) using electronic health records, we aimed to develop algorithms to identify dialysis patients using laboratory data obtained in routine practice.<br> Methods We collected clinical data of patients with an eGFR < 15 mL/min/1.73 m2 from six clinical research core hospitals across Japan: four hospitals for the derivation cohort and two for the validation cohort. The candidate factors for the classification models were identified using logistic regression with stepwise backward selection. To ensure transplant patients were not included in the non-dialysis population, we excluded individuals with the disease code Z94.0.<br> Results We collected data from 1142 patients, with 640 (56%) currently undergoing hemodialysis or peritoneal dialysis (PD), including 426 of 763 patients in the derivation cohort and 214 of 379 patients in the validation cohort. The prescription of PD solutions perfectly identified patients undergoing dialysis. After excluding patients prescribed PD solutions, seven laboratory parameters were included in the algorithm. The areas under the receiver operation characteristic curve were 0.95 and 0.98 and the positive and negative predictive values were 90.9% and 91.4% in the derivation cohort and 96.2% and 94.6% in the validation cohort, respectively. The calibrations were almost linear.<br> Conclusions We identified patients on dialysis among those with an eGFR < 15 ml/min/1.73 m2. This study paves the way for database research in nephrology, especially for patients with non-dialysis-dependent advanced CKD. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1875-8312 2025 Computed tomography versus aortography for transcatheter patent ductus arteriosus closure in adults EN Takashi Miki Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toru Miyoshi Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Teiji Akagi Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Mitsutaka Nakashima Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Rie Nakayama Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yoichi Takaya Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Koji Nakagawa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Norihisa Toh Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shinsuke Yuasa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Accurate sizing of the patent ductus arteriosus (PDA) is essential for successful transcatheter closure. While aortography is the standard imaging modality, computed tomography (CT) may offer superior anatomical visualization. This study aimed to compare the accuracy and procedural outcomes of preprocedural CT versus aortography alone in adult patients undergoing transcatheter PDA closure. We retrospectively analyzed 54 adult patients who underwent PDA closure using the Amplatzer™ Duct Occluder between 2009 and 2024. Nineteen patients were treated based on aortography alone and 35 based on preprocedural CT. We compared procedural characteristics and outcomes, including device size exchange and procedure time. A simulation study was also conducted in which two blinded implanters independently predicted occluder size based on CT and aortography, with actual implanted device size used as the reference. The CT group had significantly larger PDA sizes and implanted device sizes. Device replacement was required in three patients in the aortography group but none in the CT group. Procedure time was shorter in the CT group (60 ± 9 vs. 70 ± 14 min, p = 0.003). Simulation results showed that CT more accurately predicted the actual implanted device size (85% vs. 63%, p = 0.008). PDA size at the pulmonary artery end was significantly underestimated by aortography. Preprocedural CT improved procedural efficiency and device selection accuracy in adult PDA closure. These findings suggest that CT imaging may enhance planning and safety in transcatheter PDA interventions. No potential conflict of interest relevant to this article was reported.

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

MDPI AG Acta Medica Okayama 2504-446X 9 9 2025 Application of LMM-Derived Prompt-Based AIGC in Low-Altitude Drone-Based Concrete Crack Monitoring 660 EN Shijun Pan Shenzhen Institute for Advanced Study, UESTC, University of Electronic Science and Technology of China Zhun Fan Shenzhen Institute for Advanced Study, UESTC, University of Electronic Science and Technology of China Keisuke Yoshida Graduate School of Environmental and Life Science, Okayama University Shujia Qin Shenzhen Academy of Robotics Takashi Kojima TOKEN C.E.E. Consultants Co., Ltd. Satoshi Nishiyama Graduate School of Environmental and Life Science, Okayama University In recent years, large multimodal models (LMMs), such as ChatGPT 4o and DeepSeek R1―artificial intelligence systems capable of multimodal (e.g., image and text) human–computer interaction―have gained traction in industrial and civil engineering applications. Concurrently, insufficient real-world drone-view data (specifically close-distance, high-resolution imagery) for civil engineering scenarios has heightened the importance of artificially generated content (AIGC) or synthetic data as supplementary inputs. AIGC is typically produced via text-to-image generative models (e.g., Stable Diffusion, DALL-E) guided by user-defined prompts. This study leverages LMMs to interpret key parameters for drone-based image generation (e.g., color, texture, scene composition, photographic style) and applies prompt engineering to systematize these parameters. The resulting LMM-generated prompts were used to synthesize training data for a You Only Look Once version 8 segmentation model (YOLOv8-seg). To address the need for detailed crack-distribution mapping in low-altitude drone-based monitoring, the trained YOLOv8-seg model was evaluated on close-distance crack benchmark datasets. The experimental results confirm that LMM-prompted AIGC is a viable supplement for low-altitude drone crack monitoring, achieving >80% classification accuracy (images with/without cracks) at a confidence threshold of 0.5. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1472-6831 25 1 2025 Phosphorylated pullulan as a local drug delivery matrix for cationic antibacterial chemicals to prevent oral biofilm 1333 EN Naoko Namba-Koide Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Yasuhiro Yoshida Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Takumi Okihara Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Yusuke Kawata Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Masahiro Ito Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Takashi Ito Center for Innovative Clinical Medicine, Okayama University Hospital Kazu Takeuchi-Hatanaka Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Yuki Shinoda-Ito Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Omori Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yamamoto Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Takashiba Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Preventing oral infections, such as oral caries and periodontal disease, helps reduce the risks of various systemic diseases. In this study, the polysaccharide pullulan produced by the black yeast Aureobasidium pullulans was modified in combination with the cationic surfactant cetylpyridinium chloride (CPC) to create a local drug delivery system, and its antibacterial potential on oral bacteria was examined in vitro.<br> Methods Pullulan was phosphorylated at the CH2OH residue of α6 in the maltotriose structure and mixed with CPC. Bacterial attachment of cariogenic Streptococcus mutans on hydroxyapatite plates (HAPs) treated with the phosphorylated pullulan (PP) and CPC compound (0.01% PP and 0.001– 0.03% CPC, and vice versa) was assessed by observing bacteria using a field emission scanning electron microscope (FE-SEM) and quantified through 16 S rRNA amplification via real-time polymerase chain reaction (PCR). Additionally, the quartz crystal microbalance (QCM) method was employed to evaluate the sustained release of CPC.<br> Results PP-CPC compound maintained significant bactericidal activity even at 0.01%, which is one-fifth of the conventional applicable concentration of CPC. Additionally, a residual mixture was detected by the hydroxyapatite sensor of the crystal oscillator microbalance detector, suggesting an unknown molecular interaction that enables the sustained release of CPC after attachment to hydroxyapatite.<br> Conclusions The combination of PP and CPC may contribute to the low concentration and effective prevention of oral infections, such as dental caries. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 1536-0210 2025 Applicability of Effective Atomic Number (Z eff) Image Analysis of Coronary Plaques Measured With Photon- Counting Computed Tomography EN Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Mana Mitani Medical Support Department, Division of Radiology, Okayama University Hospital Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Kazuki Takegami Department of Radiological Technology, Yamaguchi University Hospital Yusuke Morimitsu Medical Support Department, Division of Radiology, Okayama University Hospital Noriaki Akagi Medical Support Department, Division of Radiology, Okayama University Hospital Toru Miyoshi Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Kanazawa Faculty of Life Science, Kumamoto University Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University Objective: Coronary computed tomography (CT) allows the assessment of cardiovascular risk by imaging calcified plaques in coronary arteries. Because photon-counting CT (PC-CT) can analyze the effective atomic number (Zeff) of the subject, it is expected to be applied to the analysis of plaque components. The purpose of this study was to investigate the applicability of plaque analysis based on Zeff images with continuous gradation.<br> Methods: Zeff images were generated from virtual monoenergetic images (VMIs) obtained by PC-CT. Zeff values were derived from the difference between linear attenuation coefficients (μ) at low and high energies using an in-house program. Coronary CT images of 64 plaques in 10 patients were analyzed. The Zeff score, calculated as the sum of Zeff values within the plaque region, was calculated and compared with the conventional Agatston score and mean coronary artery calcium (CAC) score.<br> Results: The systematic uncertainty of Zeff images was estimated to be ±0.08. The Zeff score of actual patient data showed strong positive correlations with the conventional Agatston and mean CAC scores. The Zeff score uses all voxel data in the plaque area, whereas conventional scores consider only data from voxels with a CT value >130. We found that the conventional scores excluded 39% of the plaque area, and the Zeff score permitted the analysis of low- and high-density plaques.<br> Conclusions: Zeff imaging was shown to be applicable to plaque analysis that reflects the entire plaque volume. This study demonstrated its technical feasibility as a compositional analysis method using the Zeff image. No potential conflict of interest relevant to this article was reported.

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

Springer Nature Switzerland Acta Medica Okayama 0303-4216 2025 Low-Threshold Raman Silicon Lasers Using Photonic Crystal High-Q Nanocavities 95 143 EN Yasushi Takahashi Okayama University Takashi Asano Kyoto University Susumu Noda Kyoto University By utilizing stimulated Raman scattering, it is possible to generate continuous-wave laser light in silicon, an indirect bandgap semiconductor. The first part of this chapter explains the mechanism of the Raman laser using a silicon resonator with a high-quality factor (Q). In the second part, the mechanism of the ultra-low threshold Raman silicon laser using a photonic crystal high-Q nanocavity is summarized, and recent advancements are explained. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0969-806X 239 2026 Helical X-ray tube trajectory estimation via image noise analysis for enhanced CT dosimetry 113260 EN Tatsuya Maeda Graduate School of Medical Sciences, Kanazawa University Kazuki Takegami Department of Radiological Technology, Yamaguchi University Hospital Sota Goto Faculty of Health Sciences, Kobe Tokiwa University Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Daiki Kobayashi Graduate School of Medical Sciences, Kanazawa University Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Kazuta Yamashita Department of Orthopedics, School of Medicine, Tokushima University Kosaku Higashino Shikoku Medical Center for Children and Adults Shinichi Morimoto MEDITEC JAPAN Co., Ltd., Yamaguchi Kosan Bld. Takeshi Konishi MEDITEC JAPAN Co., Ltd., Yamaguchi Kosan Bld. Motochika Maki MEDITEC JAPAN Co., Ltd., Yamaguchi Kosan Bld. Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University Information on the helical trajectory of the X-ray tube is necessary for accurate dose evaluation during computed tomography (CT). We aimed to propose a methodology for analyzing the trajectory of the X-ray tube. The novelty of this paper is that the incident direction of X-rays is estimated from the standard deviation (SD) distribution. The X-ray incident direction for each slice was analyzed using a distribution function of SD values, in which the analysis regions were placed in the air region. Then, the helical trajectory of the CT scan was estimated by fitting a three-dimensional helical function to the analyzed data. The robustness of our algorithm was verified through phantom studies: the analyzed X-ray incident directions were compared with instrumental log data, in which cylindrical polyoxymethylene resin phantoms and a whole-body phantom were scanned. Chest CT scanning was mimicked, in which the field of view (FOV) was set at the lung region. The procedure for analyzing the X-ray incident direction was applicable to cylindrical phantoms regardless of the phantom size. In contrast, in the case of the whole-body phantom, although it was possible to apply our procedure to the chest and abdomen regions, the shoulder slices were inappropriate to analyze. Therefore, the helical trajectory was determined based on chest and abdominal CT images. The accuracy in X-ray incident direction analysis was evaluated to be 7.5°. In conclusion, we have developed an algorithm to estimate a three-dimensional helical trajectory that can be used for dose measurements and simulations. No potential conflict of interest relevant to this article was reported.

Fuji Technology Press Ltd. Acta Medica Okayama 1883-8030 20 4 2025 High-Definition Topographic Archiving and Educational Applications in Regions Affected by the 2024 Noto Peninsula Earthquake 401 409 EN Takuro Ogura Graduate School of Education, Hyogo University of Teacher Education Hiroyuki Yamauchi Art Research Center, Ritsumeikan University Tatsuto Aoki Faculty of Regional Development Studies, Kanazawa University Nobuhisa Matta Graduate School of Education, Okayama University Kotaro Iizuka Center for Spatial Information Science, The University of Tokyo Yoshiya Iwasa Faculty of Education, University of Teacher Education Fukuoka Takayuki Takahashi International Research Institute of Disaster Science, Tohoku University Kiyomi Hayashi Faculty of Regional Development Studies, Kanazawa University Tsuyoshi Hattanji Institute of Life and Environmental Sciences, University of Tsukuba Takashi Oguchi Center for Spatial Information Science, The University of Tokyo The 2024 Noto Peninsula earthquake (Mw 7.5) caused extensive damage in Ishikawa Prefecture, Japan, and surrounding areas, with considerable coastal uplift and tsunami flooding. Past 100 years’ records show no earthquake above Mw 7.0 in the Noto Peninsula, so for everyone alive today, this event is truly without precedent. Therefore, we aimed to support disaster prevention education by developing teaching materials using unmanned aerial vehicles (UAVs) based on digitally archived topographic changes. High-definition topographic data collected from multiple UAV surveys were processed into digital and analog formats, including 3D models, spherical panorama images, and 3D printings. These materials were designed to provide detailed and intuitive representations of post-disaster landforms and were used as educational tools in schools. The learning materials were introduced during a workshop for disaster-affected teachers, featuring hands-on activities to help participants familiarize themselves with the materials, and explore their integration into geography and science classes. Feedback from participants indicated that these tools were highly effective in enhancing classroom learning. The results of this study are expected to contribute to preserving disaster records while enhancing disaster awareness in educational settings and local communities. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-0533 149 1 2025 Cerebral Braak stage and amygdala granular fuzzy astrocyte status have independent effects on neuronal 3R-tau and 4R-tau accumulations in the olfactory bulb, respectively, in cases with low to intermediate AD neuropathologic change 36 EN Osamu Yokota Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Miki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hanae Nakashima-Yasuda Okayama University Medical School Hideki Ishizu Okayama University Medical School Takashi Haraguchi Department of Neurology, National Hospital Organization Minami-Okayama Medical Center Akinori Miyashita Department of Molecular Genetics, Brain Research Institute, Niigata University Takeshi Ikeuchi Department of Molecular Genetics, Brain Research Institute, Niigata University Masato Hasegawa Dementia Research Project, Tokyo Metropolitan Institute of Medical Science Naoto Nishikawa Department of Neuropsychiatry, Okayama University Hospital Shintaro Takenoshita Department of Neuropsychiatry, Okayama University Hospital Seishi Terada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

S. Karger AG Acta Medica Okayama 1015-9770 2025 Asymptomatic intracranial vascular lesions and cognitive function in a general population of Japanese men: Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) EN Takahiro Ito Department of Radiology, Shiga University of Medical Science Akira Fujiyoshi Department of Radiology, Shiga University of Medical Science Takayoshi Ohkubo Department of Hygiene and Public Health, Teikyo University School of Medicine Akihiko Shiino Molecular Neuroscience Research Center, Shiga University of Medical Science Satoshi Shitara Department of Neurosurgery, Shiga University of Medical Science Naoko Miyagawa Department of Preventive Medicine and Public Health, Keio University School of Medicine Sayuki Torii Department of Radiology, Shiga University of Medical Science Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyoshi Segawa Department of Radiology, Shiga University of Medical Science Keiko Kondo Department of Radiology, Shiga University of Medical Science Aya Kadota Department of Radiology, Shiga University of Medical Science Ikuo Tooyama Molecular Neuroscience Research Center, Shiga University of Medical Science Yoshiyuki Watanabe Department of Radiology, Shiga University of Medical Science Kazumichi Yoshida Department of Neurosurgery, Shiga University of Medical Science Kazuhiko Nozaki Department of Neurosurgery, Shiga University of Medical Science Katsuyuki Miura Department of Radiology, Shiga University of Medical Science The SESSA Research Group Introduction: Intracranial subclinical vessel diseases are considered important indicators of cognitive impairment. However, a comprehensive assessment of various types of vessel disease, particularly in Asian populations, is lacking. We aimed to compare multiple types of intracranial vessel disease in association with cognitive function among a community-based Japanese male population. Methods: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) randomly recruited and examined a community-based cohort of Japanese men from Shiga, Japan. We analyzed those who underwent the Cognitive Abilities Screening Instrument (CASI) assessment and cranial magnetic resonance imaging/angiogram (MRI/MRA) in 2010–2015. Using MRI/MRA, we assessed lacunar infarction, microbleeds, periventricular hyperintensity (PVH), deep subcortical white matter hyperintensity (DSWMH), and intracranial artery stenosis (ICAS). We divided these subclinical cerebrovascular diseases (SCDs) into three categories according to severity. Using linear regression, we calculated the CASI score according to the grade of each vessel disease, adjusted for age and years of education. Results: In the adjusted models, CASI scores were significantly associated with both PVH and DSWMH. Specifically, multivariable-adjusted CASI scores declined across increasing severity categories of DSWMH (91.7, 91.2, and 90.4; p for trend = 0.011) and PVH (91.5, 90.4, and 89.7; p for trend = 0.006). Other SCDs did not show significant associations. In stratified analyses based on the presence or absence of each SCD, both DSWMH and PVH demonstrated significant inverse trends with CASI scores in the absence of lacunar infarcts and microbleeds and in the presence of ICAS. Additionally, among participants with PVH (+), ≥moderate ICAS was significantly associated with lower CASI scores. Conclusion: PVH and DSWMH showed significant dose-response relationships with cognitive function among community-based Japanese men. These findings suggest that white matter lesions may be an important indicator of early cognitive impairment, and severe ICAS may also play a role in those with PVH. No potential conflict of interest relevant to this article was reported.

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

Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 64 4 2024 Computed tomography findings of idiopathic multicentric Castleman disease subtypes 292 296 EN Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Noriko Iwaki Department of Hematology, National Cancer Center Hospital Katsuhide Kojima Department of Radiology, Okayama University Hospital Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Fumio Otsuka Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinobu Maeda Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University This study retrospectively evaluated the computed tomography (CT) findings of idiopathic multicentric Castleman disease (iMCD) at a single center and compared the CT findings of iMCD-TAFRO with those of iMCD-non-TAFRO. CT images obtained within 30 days before diagnostic confirmation were reviewed for 20 patients with iMCD (8 men and 12 women, mean age 52.8 ± 12.3 years, range 25–74 years). Twelve patients were diagnosed with iMCD-TAFRO, five with iMCD-idiopathic plasmacytic lymphadenopathy, and three with iMCD-not otherwise specified. CT images revealed anasarca and lymphadenopathy in all 20 patients. The iMCD-TAFRO group showed significantly higher frequencies of ascites (100% vs. 37.5%, P = 0.004), gallbladder wall edema (75.0% vs. 12.5%, P = 0.020), periportal collar (91.7% vs. 25.0%, P = 0.004), and anterior mediastinal lesions (non-mass-forming infiltrative lesions) (66.7% vs. 12.5%, P = 0.028). Para-aortic edema tended to be more frequent in patients with the iMCD-TAFRO group (83.3% vs. 37.5%, P = 0.062), while the absence of anterior mediastinal lesions tended to be more frequent in the iMCD-non-TAFRO group (16.7% vs. 62.5%, P = 0.062). These CT findings may have clinical implications for improving the accuracy and speed of iMCD diagnosis and differentiating iMCD-TAFRO from other subtypes. 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 Coronary cross-sectional area stenosis severity determined using coronary CT highly correlated with coronary functional flow reserve: a pilot study 26737 EN Takuto Koumoto Division of Radiation, Okayama Heart Clinic Shozo Kusachi Okayama University Graduate School of Health Sciences Takumi Tomiya Division of Cardiovascular Intervention, Okayama Heart Clinic Takuya Akagi Division of Cardiovascular Intervention, Okayama Heart Clinic Hiroshi Kawamura Division of Cardiovascular Medicine, Okayama Heart Clinic Satoshi Hirohata Okayama University Graduate School of Health Sciences Hirosuke Yamaji Division of Cardiovascular Medicine, Okayama Heart Clinic Takashi Murakami Division of Cardiovascular Medicine, Okayama Heart Clinic Shigeshi Kamikawa Division of Cardiovascular Intervention, Okayama Heart Clinic Masaaki Murakami Division of Cardiovascular Intervention, Okayama Heart Clinic Fractional flow reserve (FFR) is the gold standard for assessing the physiological significance of coronary stenosis. We examined the potential correlation between digitally measured coronary cross-sectional area stenosis using coronary computed tomography (CT) angiography and FFR. We analyzed data of 32 consecutive patients with stenoses who underwent invasive FFR determination. The cross-sectional area was assessed using 128-slice coronary detector-based spectral CT angiography. Power analysis revealed that the sample size enabled the detection of an area under the receiver operating characteristic (ROC) curve (AUC) of 0.90. FFR ≤ 0.8 and > 0.8 were defined as FFR-positive and FFR-negative, respectively. Intra- and interobserver differences were negligible. Percentage cross-sectional area stenosis was calculated as 100 × (A−B)/A, where A is the cross-sectional area at non-stenotic pre-stenotic segment and B is the cross-sectional area of the most severe stenotic lesion. AUC indicated that percentage cross-sectional area stenosis effectively discriminated between FFR-positive and FFR-negative cases, yielding a sensitivity of 0.882 and specificity of 0.933 at a cutoff of 50% area reduction, with an AUC of 0.976. Lesions with less than 45% cross-sectional area stenosis on coronary CT angiography were not FFR-positive. When ROC analysis was conducted for lesion characteristics, AUC did not significantly improve. In conclusion, the percent coronary cross-sectional area stenosis measured using coronary CT angiography distinguished between FFR-positive and FFR-negative lesions with high accuracy. The severity of coronary cross-sectional area stenosis determined using CT angiography is clinically useful for predicting FFR. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 1076-0296 31 2025 Activated Clotting Time Requires Adaptation Across Altered Measurement Devices: Determination of Appropriate Range During Atrial Fibrillation Ablation EN Haruna Sakanoue Department of Nursing, Okayama Heart Clinic Hirosuke Yamaji Heart Rhythm Center, Okayama Heart Clinic Sayaka Okamoto Department of Nursing, Okayama Heart Clinic Kumi Okano Department of Nursing, Okayama Heart Clinic Yuka Fujita Department of Nursing, Okayama Heart Clinic Shunichi Higashiya Heart Rhythm Center, Okayama Heart Clinic Takashi Murakami Heart Rhythm Center, Okayama Heart Clinic Satoshi Hirohata Department of Medical Technology, Okayama University Graduate School of Health Sciences Shozo Kusachi Department of Medical Technology, Okayama University Graduate School of Health Sciences Background: Methods for measuring activated clotting time (ACT) are not yet standardized.<br> Objectives: To adjust and compare values between two measurement systems and to optimize ACT during atrial fibrillation (AF) ablation.<br> Methods: Two systems were compared: electromagnetic detection using a rotating tube (EM system; Hemochron Response) and photo-optical detection using a cartridge immersed in blood (PO system; ACT CA-300TM).<br> Results: ACT was measured simultaneously in 124 instances in 53 patients before and during AF ablations using both methods. A linear regression analysis showed ACT (EM system) = 1.19 × ACT (PO system) + 9.03 (p < .001, r = 0.90). Bland–Altman plots indicated an average difference of 50 s between the two systems. In 3364 ACT measurements from 1161 ablations, the EM system recorded a mean ACT of 320 ± 44 s (range 156-487 s). Estimating the target range as mean ± 1 SD range, the EM system's range was 275-365 s, in 5-s increments. The pre-ablation ACT measured on the EM system was 143 ± 28 s (115-170 s). Cardiac tamponade occurred in 4 out of 2085 ablations (0.19%) over 5 years, with ACT values ranging from 330 to 391 s on the EM system. Based on these findings, the estimated optimal ACT range for the PO system was adjusted to 225-300 s to align with the EM system's range of 275-365 s.<br> Conclusions: ACT target ranges should be system-specific, and direct extrapolation between devices is not recommended. Adjustment is clinically necessary when switching systems. No potential conflict of interest relevant to this article was reported.

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

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

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

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Association between cesarean delivery and childhood allergic diseases in a longitudinal population-based birth cohort from Japan 19206 EN Kei Tamai Department of Epidemiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Naomi Matsumoto Department of Epidemiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takashi Mitsui Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hisashi Masuyama Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takashi Yorifuji Department of Epidemiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine The association between cesarean delivery and childhood allergic diseases, such as atopic dermatitis, food allergy, and bronchial asthma, remains unclear, with limited evidence from Asian populations. We analyzed population-based data of 2,114 children born in Japan in 2010 from the Longitudinal Survey of Babies in the 21st Century, linked to the Perinatal Research Network Database. Comparisons were made between children born by cesarean delivery and those born vaginally. Longitudinal outcomes were atopic dermatitis, food allergy, and bronchial asthma during childhood for each age group up to 9 years of age. We performed Poisson regression analyses with robust variance, and adjusted for child and parent variables, followed by supplementary analyses using generalized estimating equations (GEE). Children born by cesarean delivery did not have a higher risk of most outcomes compared to those born vaginally. GEE analysis found no association between cesarean delivery and atopic dermatitis (adjusted risk ratio [aRR] 0.8, 95% confidence interval [CI] 0.5–1.2), food allergy (aRR 1.1, 95% CI 0.7–1.7), bronchial asthma (aRR 1.0, 95% CI 0.8–1.4), or allergic rhinoconjunctivitis (aRR 0.9, 95% CI 0.8–1.1). This study shows no clear evidence of an association between delivery mode and childhood allergic diseases in Japan. No potential conflict of interest relevant to this article was reported.

Japan Atherosclerosis Society Acta Medica Okayama 1340-3478 32 5 2025 ChatGPT Responses to Clinical Questions in the Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Disease 2022 567 579 EN Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mari Fukuda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Minako Kinuta Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideyuki Kanda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aims: Artificial intelligence is increasingly used in the medical field. We assessed the accuracy and reproducibility of responses by ChatGPT to clinical questions (CQs) in the Japan Atherosclerosis Society Guidelines for Prevention Atherosclerotic Cardiovascular Diseases 2022 (JAS Guidelines 2022).<br> Methods: In June 2024, we assessed responses by ChatGPT (version 3.5) to CQs, including background questions (BQs) and foreground questions (FQs). Accuracy was assessed independently by three researchers using six-point Likert scales ranging from 1 (“completely incorrect”) to 6 (“completely correct”) by evaluating responses to CQs in Japanese or translated into English. For reproducibility assessment, responses to each CQ asked five times separately in a new chat were scored using six-point Likert scales, and Fleiss kappa coefficients were calculated.<br> Results: The median (25th–75th percentile) score for ChatGPT’s responses to BQs and FQs was 4 (3–5) and 5 (5–6) for Japanese CQs and 5 (3–6) and 6 (5–6) for English CQs, respectively. Response scores were higher for FQs than those for BQs (P values ＜0.001 for Japanese and English). Similar response accuracy levels were observed between Japanese and English CQs (P value 0.139 for BQs and 0.586 for FQs). Kappa coefficients for reproducibility were 0.76 for BQs and 0.90 for FQs.<br> Conclusions: ChatGPT showed high accuracy and reproducibility in responding to JAS Guidelines 2022 CQs, especially FQs. While ChatGPT primarily reflects existing guidelines, its strength could lie in rapidly organizing and presenting relevant information, thus supporting instant and more efficient guideline interpretation and aiding in medical decision-making. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 64 15 2025 Clinical and Genetic Analyses of SPG7 in Japanese Patients with Undiagnosed Ataxia 2290 2294 EN Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Rimi Hino Department of Neurology, Graduate School of Medicine, The University of Tokyo Go Fujino Department of Neurology, Graduate School of Medicine, The University of Tokyo Yuto Sakai Department of Neurology, International University of Health and Welfare Mita Hospital Jun Mitsui Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nobue K. Iwata Department of Neurology, International University of Health and Welfare Mita Hospital Shoji Tsuji Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Objective Spastic paraplegia 7 (SPG7) is an autosomal recessive neurodegenerative disorder caused by biallelic pathogenic variants in SPG7. It is predominantly characterized by adult-onset slowly progressive spastic paraparesis. While SPG7 presenting with ataxia with or without spasticity is relatively common in Europe and North America, it is considered rare in Japan. This study aimed to identify SPG7 patients among those with undiagnosed ataxia within the Japanese population.<br> Methods We retrospectively selected 351 patients with undiagnosed ataxia, excluding those with secondary and common spinocerebellar ataxia. Whole-exome sequence analysis was conducted, and homozygosity of the identified variants was confirmed using droplet digital polymerase chain reaction (ddPCR).<br> Results Among the 351 patients, 2 were diagnosed with SPG7, and homozygosity was confirmed by ddPCR. Both patients carried homozygous pathogenic variants in SPG7: c.1948G>A, p.Asp650Asn, and c.1192C>T, p.Arg398Ter (NM_003119.4). Clinically, both patients presented with progressive ataxia. In addition, Patient 1 exhibited partial ophthalmoplegia and spastic paraparesis, whereas Patient 2 demonstrated cerebellar ataxia without spasticity.<br> Conclusion The rarity of SPG7 in Japan may be attributed to variation in the minor allele frequency of the c.1529C>T, p.Ala510Val variant, which is more prevalent in Europe and North America than in other areas. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0022-510X 472 2025 Clinical, neuroimaging and genetic findings in the Japanese case series of CLCN2-related leukoencephalopathy 123486 EN Kenta Orimo Department of Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo Takusei Cho Department of Neurology, Graduate School of Medicine, The University of Tokyo Hiroya Naruse Department of Neurology, Graduate School of Medicine, The University of Tokyo Yoshio Sakiyama Division of Neurology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University Kensho Sumi Department of Neurology, Mitsui Memorial Hospital Naohiro Uchio Department of Neurology, Mitsui Memorial Hospital Akane Satake Department of Neurology, Fuefuki Central Hospital Yoshihisa Takiyama Department of Neurology, Fuefuki Central Hospital Takuya Matsushita Department of Neurology, Kochi Medical School, Kochi University Yosuke Omae Genome Medical Science Project, National Center for Global Health and Medicine Yosuke Kawai Genome Medical Science Project, National Center for Global Health and Medicine Katsushi Tokunaga Genome Medical Science Project, National Center for Global Health and Medicine Jun Mitsui Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Graduate School of Medicine, The University of Tokyo Shoji Tsuji Department of Neurology, Graduate School of Medicine, The University of Tokyo Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Biallelic loss-of-function variants in CLCN2 lead to CLCN2-related leukoencephalopathy (CC2L), also called leukoencephalopathy with ataxia (LKPAT). CC2L is characterized clinically by a spectrum of clinical presentations including childhood- to adult-onset mild ataxia, spasticity, cognitive decline, and vision loss as well as typical MRI findings of symmetrical high signal intensities on the DWIs/T2WIs of the middle cerebellar peduncles (MCPs). We searched for pathogenic variants of CLCN2 in a case series of undiagnosed leukoencephalopathy accompanied by MCP signs, which led to the identification of four Japanese patients with CC2L. All the patients carried at least one allele of c.61dupC (p.Leu21Profs*27) in CLCN2, including compound heterozygosity with either the novel pathogenic variant c.983 + 2 T > A or the previously reported pathogenic variant c.1828C > T (p.Arg610*). Of note, all the four previously reported cases from Japan also harbored c.61dupC, and no reports of this variant have been documented from outside Japan. The allele frequency of c.61dupC in the Japanese population is 0.002152, raising the possibility of a relatively high prevalence of CC2L in Japan. Patients in this study developed symptoms after the age of 30, and demonstrated neurological signs including cerebellar ataxia, pyramidal signs, and mild cognitive impairment, consistent with previous reports. One male patient had two children, supporting preserved fertility, and another patient had calcifications in the cerebral and cerebellar surfaces. These findings provide valuable insights into the broader clinical and genetic spectra of CC2L in the Japanese population, and emphasize the importance of considering this disease in the differential diagnoses of leukoencephalopathy with MCP signs. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 0969-806X 238 2026 Bone-enhanced high contrast X-ray images derived from attenuation estimation related to ultra-low energy X-rays – An application of an energy-resolving photon-counting detector (ERPCD) 113243 EN Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Takashi Asahara Faculty of Health Sciences, Okayama University Tatsuya Maeda Graduate School of Medical Sciences, Kanazawa University Daiki Kobayashi Graduate School of Medical Sciences, Kanazawa University Sota Goto Faculty of Health Sciences, Kobe Tokiwa University Tomonobu Haba Faculty of Radiological Technology, School of Medical Science, Fujita Health University Yuki Kanazawa Faculty of Life Science, Kumamoto University Shuichiro Yamamoto JOB CORPORATION Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University Purpose: X-ray diagnosis in medicine is often used for bone diagnosis based on qualitative observation analysis. However, there are often cases where the contrast of bones is reduced because of the existence of soft-tissues, making it difficult to accurately diagnose the bone conditions. Although the algorithm for bone extraction images was proposed using an energy-resolving photon-counting detector (ERPCD), this algorithm can depict “one” bone material (such as hydroxyapatite under the assumption), and it is difficult to adequately depict other components. The purpose of this study is to develop an algorithm for bone-enhanced high-contrast images that can be virtually represented by the attenuation of extremely low-energy X-rays without making any special assumptions.<br> Methods: High-contrast images were virtually generated based on the attenuation rate of ultra-low energy X-rays. It was determined by fitting the mass attenuation coefficient (μ/ρ) curve to the X-ray attenuation values (μt values) measured at middle (30–40 keV) and high (40–60 keV) energy windows, and extrapolating the μt values to those for the low energy region (E = 5–20 keV). When performing the extrapolation, the effective atomic number (Zeff ) of the object was taken into consideration. The methodology was validated by simulating X-ray projections using a digital human body phantom. The frequency of correspondence between the pixel values in the high-contrast image and the Zeff image was analyzed for each pixel.<br> Results: We succeeded in creating virtual high-contrast X-ray images that reflect the image contrast of monochromatic X-rays of 5–20 keV. It was confirmed that the pixel values in the high-contrast image corresponding to an Zeff = 7.5 (soft-tissue) were completely separated from those corresponding to an Zeff = 9 (bone). The optimization of the energy related to the high contrast images was performed based on the contrast-to-noise ratio (CNR) analysis. The high contrast image with 10 keV showed a good CNR value.<br> Conclusions: Based on the analysis of the attenuation information of middle and high-energy X-rays measured by ERPCDs, we succeeded in creating a novel algorithm that can generate a virtual monochromatic image with high contrast. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0969-806X 239 2026 Counting-loss correction procedure of X-ray imaging detectors with consideration for the effective atomic number of biological objects 113237 EN Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Daiki Kobayashi Graduate School of Medical Sciences, Kanazawa University Tatsuya Maeda Graduate School of Medical Sciences, Kanazawa University Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Sota Goto Faculty of Health Science, Kobe Tokiwa University Yuki Kanazawa Faculty of Life Science, Kumamoto University Akitoshi Katsumata Oral Radiology and Artificial Intelligence, Asahi University Shuichiro Yamamoto JOB CORPORATION Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University It is necessary to correct counting loss caused by the pulse pile-up effect and dead time when using energy-resolving photon-counting detectors (ERPCDs) under “high-counting-rate” conditions in medical and/or industrial settings. We aimed to develop a novel counting-loss correction procedure in which biological objects having effective atomic numbers (Zeff values) of 6.5–13.0 are measured with polychromatic X-rays. To correct for counting loss, such a procedure must theoretically estimate the count value of an ideal X-ray spectrum without counting loss. In this study, we estimated the ideal X-ray spectrum by focusing on the following two points: (1) the X-ray attenuation in an object (Zeff values of 6.5–13.0) and (2) the detector response. Virtual materials having intermediate atomic numbers between 6.5 and 13.0 were generated by using a mixture of polymethylmethacrylate (PMMA, Zeff = 6.5) and aluminum (Al, Zeff = 13.0). We then constructed an algorithm that can perform the counting-loss correction based on the object’s true Zeff value. To demonstrate the applicability of our procedure, we analyzed investigational objects consisting of PMMA and Al using a prototype ERPCD system. A fresh fish sample was also analyzed. The Zeff values agree with the theoretical values within an accuracy of Zeff ±1. In conclusion, we have developed a highly accurate procedure for correcting counting losses for the quantitative X-ray imaging of biological objects. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 Organ Donation after Extracorporeal Cardiopulmonary Resuscitation: Clinical and Ethical Perspectives 221 229 EN Tetsuya Yumoto Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takafumi Obara Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinori Kosaki Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohei Ageta Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohei Tsukahara Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Review 10.18926/AMO/69147 Extracorporeal cardiopulmonary resuscitation (ECPR) has evolved into a life-saving therapy for select cardiac arrest patients, yet a growing body of evidence suggests it also holds promise as a bridge to organ donation in non-survivors. This review explores the clinical outcomes, ethical complexities, and evolving policies surrounding organ donation after ECPR. We summarize recent international and Japanese data demonstrating favorable graft function from ECPR donors, with the exception of lung transplantation. The ethical challenges ― particularly those involving brain death determination on extracorporeal membrane oxygenation and adherence to the dead donor rule ― are discussed in the context of Japan’s recent regulatory reforms. Additionally, we highlight the importance of structured end-of-life communication through multidisciplinary team meetings in facilitating ethically sound transitions from rescue efforts to donation pathways. Moving forward, improvements in donor management, standardized legal frameworks, and public and professional education are essential to optimizing the life-saving and life-giving potential of ECPR. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2589-9864 31 2025 Investigation of the relationship between 0.5–1200 Hz signal characteristics of cortical high-frequency oscillations and epileptogenicity through multivariate analysis 100776 EN Takashi Shibata Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Hiroki Tsuchiya Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Mari Akiyama Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Tomoyuki Akiyama Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Masao Matsuhashi Department of Epilepsy, Movement Disorders and Physiology, Graduate School of Medicine, Kyoto University Katsuhiro Kobayashi Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Fast ripples (FRs) (250–500 Hz) on the electroencephalogram (EEG) are closely related to epileptogenicity and are important to determine cortical regions resected in epilepsy surgery. However, FR-related epileptogenicity may be variable, and may depend on information associated with FRs. We enrolled nine epilepsy patients who had undergone intracranial 5 kHz-sampling-rate EEG for surgical treatment and had final Engel class I outcomes. Three electrodes were selected from each epileptogenic area (EA) and the unlikely EA (the region outside the EA) in each patient. Up to 100 candidate FRs were automatically detected from interictal nocturnal EEG at each of the selected electrodes and were visually reviewed independently by two researchers. Multivariate logistic regression analysis was performed using the frequency and log-power value of the corresponding FRs, presence of concurrent spike, ripple, very-high-frequency oscillations (vHFO)1 (500–600 Hz), and vHFO2 (600–1200 Hz), and whether the timing of the spectral peak of corresponding FRs was in the peak–trough or trough–peak transition of each slow activity (0.5–1, 1–2, 2–3, 3–4, and 4–8 Hz) as independent variables. Factors significantly related to epileptogenicity were FR power, the concurrent presence of spike and vHFO2, coupling with 0.5–1 and 1–2 Hz slow waves in the peak–trough transition, and coupling with 3–4 and 4–8 Hz slow waves in the trough–peak transition. Multifactorial analysis of FRs may increase their usefulness, potentially leading to improved treatment outcomes in epilepsy surgery. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0387-7604 47 1 2025 Hypotheses of pathophysiological mechanisms in epileptic encephalopathies: A review 104318 EN Katsuhiro Kobayashi Department of Pediatrics, Asahigawaso Rehabilitation and Medical Center Takashi Shibata Department of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroki Tsuchiya Department of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mari Akiyama Department of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoyuki Akiyama Department of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Introduction: Epileptic encephalopathy (EE) is a serious clinical issue that manifests as part of developmental and epileptic encephalopathy (DEE), particularly in childhood epilepsy. In EE, neurocognitive functions and behavior are impaired by intense epileptiform electroencephalogram (EEG) activity. Hypotheses of pathophysiological mechanisms behind EE are reviewed to contribute to an effective solution for EE.<br> Review: Current hypotheses are as follows: 1) neuronal dysfunction based on genetic abnormalities that may affect neurocognitive functions and epilepsy separately; 2) impairment of synaptic homeostasis during sleep that may be responsible for DEE/EE with spike-and-wave activation in sleep; 3) abnormal subcortical regulation of the cerebral cortex; 4) abnormal cortical metabolism and hemodynamics with impairment of the neural network including default mode network; 5) neurotransmitter imbalance and disordered neural excitability; 6) the effects of neuroinflammation that may be caused by epileptic seizures and in turn aggravate epileptogenesis; 7) the interaction between physiological and pathological high-frequency EEG activity; etc. The causal relationship between epileptiform EEG activity and neurocognitive dysfunctions is small in DEE based on genetic abnormalities and it is largely unestablished in the other hypothetical mechanisms.<br> Conclusion: We have not yet found answers to the question of whether the single-central or multiple derangements are present and what seizures and intense epileptiform EEG abnormalities mean in EE. We need to continue our best efforts in both aspects to elucidate the pathophysiological mechanisms of DEE/EE and further develop epilepsy treatment and precision medicine. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0340-5354 272 1 2024 Genetic and functional analyses of SPTLC1 in juvenile amyotrophic lateral sclerosis 36 EN So Okubo Department of Neurology, Graduate School of Medicine, The University of Tokyo Hiroya Naruse Department of Neurology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Sudo Department of Neurology, Graduate School of Medicine, The University of Tokyo Kayoko Esaki Department of Biotechnology and Life Sciences, Faculty of Biotechnology and Life Sciences, Sojo University Jun Mitsui Department of Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Wataru Satake Department of Neurology, Graduate School of Medicine, The University of Tokyo Peter Greimel Laboratory for Cell Function Dynamics, RIKEN Centre for Brain Sciences Nanoka Shingai Division of Applied Life Science, Graduate School of Engineering, Sojo University Yasushi Oya Department of Neurology, National Center of Neurology and Psychiatry Takeo Yoshikawa Laboratory of Molecular Psychiatry, RIKEN Center for Brain Science Shoji Tsuji Department of Neurology, Graduate School of Medicine, The University of Tokyo Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Introduction Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of the motor system. Pathogenic variants in SPTLC1, encoding a subunit of serine palmitoyltransferase, cause hereditary sensory and autonomic neuropathy type 1 (HSAN1), and have recently been associated with juvenile ALS. SPTLC1 variants associated with ALS cause elevated levels of sphinganines and ceramides. Reports on ALS associated with SPTLC1 remain limited. This study aimed to investigate the frequency of SPTLC1 variants in ALS and relevant clinical characteristics.<br> Methods We analyzed whole-exome and whole-genome sequence data from 40 probands with familial ALS and 413 patients with sporadic ALS without previously identified causative variants. Reverse transcription polymerase chain reaction (RT-PCR) analysis and droplet digital PCR (ddPCR) were used to assess splicing and mosaicism, respectively. Plasma sphingolipid levels were quantified to analyze biochemical consequences.<br> Results The heterozygous c.58G>A, p.Ala20Thr variant was identified in a 21-year-old Japanese female patient presenting with symmetric weakness which slowly progressed over 15 years. RT-PCR analysis showed no splice defects. Plasma sphingolipid levels in the patient were significantly increased compared to her asymptomatic parents. ddPCR revealed that the asymptomatic father harbored a mosaic variant with 17% relative mutant allele abundance in peripheral blood leukocytes.<br> Conclusions We identified a pathogenic c.58G>A, p.Ala20Thr SPTLC1 variant in a patient with juvenile ALS, likely inherited from an asymptomatic parent with mosaicism. Lipid analysis results are consistent with previous findings on SPTLC1-associated ALS. Further studies are necessary to determine the clinical effect of mosaic variants of SPTLC1. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 64 14 2025 Wilson's Disease Preceded by Schizophrenia-like Symptoms with Frontal-dominant Leukoencephalopathy 2240 2244 EN Ryoji Miyano Department of Neurology, Graduate School of Medicine, The University of Tokyo Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Satomi Obata Department of Neurology, Graduate School of Medicine, The University of Tokyo Hiroaki Koyama Department of Radiology, Graduate School of Medicine, The University of Tokyo Yudai Nakai Department of Radiology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akatsuki Kubota Department of Neurology, Graduate School of Medicine, The University of Tokyo Jun Shimizu Department of Neurology, Graduate School of Medicine, The University of Tokyo Kaori Sakuishi Department of Neurology, Graduate School of Medicine, The University of Tokyo Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo We herein report a 26-year-old man diagnosed with Wilson's disease (WD), initially treated for schizophrenia for 11 years. At 26 years old, he was admitted because of status epilepticus. Brain magnetic resonance imaging revealed frontal-dominant leukoencephalopathy with cystic changes and basal ganglia atrophy. The diagnosis of WD was confirmed based on neuropsychiatric symptoms, Kayser-Fleischer rings, abnormal copper metabolism, and a genetic analysis of ATP7B. Psychotic symptoms in WD can precede neurological manifestations, and extrapyramidal signs may be mistaken for drug-induced Parkinsonism. WD should be considered in patients presenting with progressive Parkinsonism preceded by schizophrenia-like psychiatric symptoms. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0028-0836 638 8049 2025 Immune evasion through mitochondrial transfer in the tumour microenvironment 225 236 EN Hideki Ikeda Division of Cell Therapy, Chiba Cancer Center Research Institute Katsushige Kawase Division of Cell Therapy, Chiba Cancer Center Research Institute Tatsuya Nishi Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomofumi Watanabe Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keizo Takenaga Division of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute Takashi Inozume Division of Cell Therapy, Chiba Cancer Center Research Institute Takamasa Ishino Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sho Aki Division of Nutriomics and Oncology, RCAST, The University of Tokyo Jason Lin Division of Cell Therapy, Chiba Cancer Center Research Institute Shusuke Kawashima Division of Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan Department of Dermatology, Graduate School of Medicine, Chiba University Joji Nagasaki Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Youki Ueda Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinichiro Suzuki Department of Medical Oncology, Kindai University Faculty of Medicine Hideki Makinoshima Tsuruoka Metabolomics Laboratory, National Cancer Center Makiko Itami Department of Surgical Pathology, Chiba Cancer Center Yuki Nakamura Division of Cell Therapy, Chiba Cancer Center Research Institute Yasutoshi Tatsumi Division of Cell Therapy, Chiba Cancer Center Research Institute Yusuke Suenaga Laboratory of Evolutionary Oncology, Chiba Cancer Center Research Institute Takao Morinaga Division of Cell Therapy, Chiba Cancer Center Research Institute Akiko Honobe-Tabuchi Department of Dermatology, Faculty of Medicine, University of Yamanashi Takehiro Ohnuma Department of Dermatology, Faculty of Medicine, University of Yamanashi Tatsuyoshi Kawamura Department of Dermatology, Faculty of Medicine, University of Yamanashi Yoshiyasu Umeda Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center Yasuhiro Nakamura Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center Yukiko Kiniwa Department of Dermatology, Shinshu University School of Medicine Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Hidetoshi Hayashi Department of Medical Oncology, Kindai University Faculty of Medicine Jun-ichiro Ikeda Department of Diagnostic Pathology, Graduate School of Medicine, Chiba University Toyoyuki Hanazawa Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine Shinichi Toyooka Department of General Thoracic Surgery and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Mano Division of Cellular Signalling, National Cancer Center Research Institute Takuji Suzuki Department of Respirology, Graduate School of Medicine, Chiba University Tsuyoshi Osawa Division of Nutriomics and Oncology, RCAST, The University of Tokyo Masahito Kawazu Division of Cell Therapy, Chiba Cancer Center Research Institute Yosuke Togashi Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Cancer cells in the tumour microenvironment use various mechanisms to evade the immune system, particularly T cell attack1. For example, metabolic reprogramming in the tumour microenvironment and mitochondrial dysfunction in tumour-infiltrating lymphocytes (TILs) impair antitumour immune responses2,3,4. However, detailed mechanisms of such processes remain unclear. Here we analyse clinical specimens and identify mitochondrial DNA (mtDNA) mutations in TILs that are shared with cancer cells. Moreover, mitochondria with mtDNA mutations from cancer cells are able to transfer to TILs. Typically, mitochondria in TILs readily undergo mitophagy through reactive oxygen species. However, mitochondria transferred from cancer cells do not undergo mitophagy, which we find is due to mitophagy-inhibitory molecules. These molecules attach to mitochondria and together are transferred to TILs, which results in homoplasmic replacement. T cells that acquire mtDNA mutations from cancer cells exhibit metabolic abnormalities and senescence, with defects in effector functions and memory formation. This in turn leads to impaired antitumour immunity both in vitro and in vivo. Accordingly, the presence of an mtDNA mutation in tumour tissue is a poor prognostic factor for immune checkpoint inhibitors in patients with melanoma or non-small-cell lung cancer. These findings reveal a previously unknown mechanism of cancer immune evasion through mitochondrial transfer and can contribute to the development of future cancer immunotherapies. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1434-5161 69 12 2024 Association study of GBA1 variants with MSA based on comprehensive sequence analysis -Pitfalls in short-read sequence analysis depending on the human reference genome- 613 621 EN Kenta Orimo Department of Neurology, Graduate School of Medicine, The University of Tokyo Jun Mitsui Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Masaki Tanaka Institute of Medical Genomics, International University of Health and Welfare Junko Nomoto Institute of Medical Genomics, International University of Health and Welfare Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Omae Genome Medical Science Project, National Center for Global Health and Medicine Yosuke Kawai Genome Medical Science Project, National Center for Global Health and Medicine Katsushi Tokunaga Genome Medical Science Project, National Center for Global Health and Medicine NCBN Controls WGS Consortium 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 Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by various combinations of autonomic failure, parkinsonism, and cerebellar ataxia. To elucidate variants associated with MSA, we have been conducting short-read-based whole-genome sequence analysis. In the process of the association studies, we initially focused on GBA1, a previously proposed susceptibility gene for MSA, to evaluate whether GBA1 variants can be efficiently identified despite its extraordinarily high homology with its pseudogene, GBA1LP. To accomplish this, we conducted a short-read whole-genome sequence analysis with alignment to GRCh38 as well as Sanger sequence analysis and compared the results. We identified five variants with inconsistencies between the two pipelines, of which three variants (p.L483P, p.A495P–p.V499V, p.L483_M489delinsW) were the results of misalignment due to minor alleles in GBA1P1 registered in GRCh38. The miscalling events in these variants were resolved by alignment to GRCh37 as the reference genome, where the major alleles are registered. In addition, a structural variant was not properly identified either by short-read or by Sanger sequence analyses. Having accomplished correct variant calling, we identified three variants pathogenic for Gaucher disease (p.S310G, p.L483P, and p.L483_M489delinsW). Of these variants, the allele frequency of p.L483P (0.003) in the MSA cases was higher than that (0.0011) in controls. The meta-analysis incorporating a previous report demonstrated a significant association of p.L483P with MSA with an odds ratio of 2.85 (95% CI; 1.05 – 7.76, p = 0.0400). No potential conflict of interest relevant to this article was reported.

Japanese Circulation Society Acta Medica Okayama 1346-9843 88 9 2024 Morphological Features of Patent Foramen Ovale Compared Between Older and Young Patients With Cryptogenic Ischemic Stroke 1398 1405 EN Mitsutaka Nakashima Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Takaya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Nakayama Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Tsuji Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Teiji Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Miki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: The morphology of a patent foramen ovale (PFO) with a high-risk for cryptogenic ischemic stroke (CS) is an important factor in the selection of patients for transcatheter closure, but the morphological features of PFO in older patients with a history of CS are less known because the most data are obtained from younger patients.<br> Methods and Results: The study included 169 patients who had a history of CS and PFO. The prevalence of high-risk morphologies of PFO assessed by transesophageal echocardiography was compared between patients aged ≥60 years and patients aged <60 years. We also assessed the presence of septal malalignment of PFO on the aortic wall. The probability of CS due to PFO was evaluated using the PFO-Associated Stroke Causal Likelihood classification system. Patients aged ≥60 years had a significantly higher prevalence of atrial septal aneurysm than patients aged <60 years. The prevalence of large right-to-left shunt, long-tunnel of PFO, or Eustachian valve or Chiari’s network was similar between patients aged ≥60 years and <60 years. Septal malalignment was observed more frequently in patients aged ≥60 years than in those <60 years old. Nearly 90% of patients aged ≥60 years were classified as ‘possible’ in the PFO-Associated Stroke Causal Likelihood classification system.<br> Conclusions: High-risk morphologies of PFO are common in older patients with a history of CS, as well as in younger patients. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-0533 150 1 2025 Biallelic variants in DNAJC7 cause familial amyotrophic lateral sclerosis with the TDP-43 pathology 19 EN Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Osamu Yokota Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daiki Ousaka Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hongming Sun Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Haraguchi Department of Neurology, National Hospital Organisation Minami-Okayama Medical Centre Ricardo Satoshi Ota-Elliott Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chika Matsuoka Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohito Kawano Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hanae Nakashima-Yasuda Department of Psychiatry, Zikei Hospital Yusuke Fukui Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yumiko Nakano Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuta Morihara Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masato Hasegawa Department of Brain and Neurosciences, Tokyo Metropolitan Institute of Medical Science Yasuyuki Hosono Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seishi Terada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons. ALS pathology primarily involves the failure of protein quality control mechanisms, leading to the accumulation of misfolded proteins, particularly TAR DNA-binding protein 43 (TDP-43). TDP-43 aggregation is a central pathological feature of ALS. Maintaining protein homeostasis is critical and facilitated by heat shock proteins (HSPs), particularly the HSP40 family, which includes co-chaperones such as DNAJC7. Here, we report a family with three siblings affected by ALS who carry a homozygous c.518dupC frameshift variant in DNAJC7, a member of the HSP40 family. All three patients exhibited progressive muscle weakness, limb atrophy, bulbar palsy, and respiratory failure. Pathological examination revealed degeneration of both upper and lower motor neurons, with phosphorylated TDP-43-positive neuronal cytoplasmic inclusions in the frontal and temporal cortices. Immunoblot analysis were consistent with a type B pattern of phosphorylated TDP-43 in the precentral gyrus. Immunohistochemistry and RNA sequencing analyses demonstrated a substantial reduction in DNAJC7 expression at both the protein and RNA levels in affected brain regions. In a TDP-43 cell model, DNAJC7 knockdown impaired the disassembly of TDP-43 following arsenite-induced stress, whereas DNAJC7 overexpression suppressed the assembly and promoted the disassembly of arsenite-induced TDP-43 condensates. Furthermore, in a zebrafish ALS model, dnajc7 knockdown resulted in increased TDP-43 aggregation in motor neurons and reduced survival. To the best of our knowledge, this study provides the first evidence linking biallelic loss-of-function variants in DNAJC7 to familial ALS with TDP-43 pathology. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1201-9712 154 2025 Secondary pneumothorax due to Aspergillus welwitschiae in a lung transplant recipient 107863 EN Shinnosuke Fukushima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Sayaka Ban Medical Mycology Research Center, Chiba University Takashi Yaguchi Medical Mycology Research Center, Chiba University Akira Watanabe Medical Mycology Research Center, Chiba University Shin Tanaka Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Seiichiro Sugimoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

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

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

JMIR Publications Inc. Acta Medica Okayama 2561-326X 9 2025 Usefulness of Interventions Using a Smartphone Cognitive Behavior Therapy Application for Children With Mental Health Disorders: Prospective, Single-Arm, Uncontrolled Clinical Trial e60943 EN Shinichiro Nagamitsu Department of Pediatrics, Faculty of Medicine, Fukuoka University Ayumi Okada Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoichi Sakuta Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center Ryuta Ishii Department of Pediatrics & Child Health, Kurume University, School of Medicine Kenshi Koyanagi Nagasaki Prefectural Center of Medicine and Welfare for Children Chizu Habukawa Department of Pediatric Allergy, Minami Wakayama Medical Center Takashi Katayama L2B Inc Masaya Ito National Center for Cognitive Behavior Therapy and Research, National Center of Neurology and Psychiatry Ayako Kanie National Center for Cognitive Behavior Therapy and Research, National Center of Neurology and Psychiatry Ryoko Otani Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center Takeshi Inoue Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center Tasuku Kitajima Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center Naoki Matsubara Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center Chie Tanaka Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chikako Fujii Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshie Shigeyasu Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Michiko Matsuoka Department of Neuropsychiatry, Kurume University School of Medicine Tatsuyuki Kakuma Biostatistics Center, Kurume University Masaru Horikoshi National Center for Cognitive Behavior Therapy and Research, National Center of Neurology and Psychiatry Background: The prevalence of mental health disorders among children in Japan has increased rapidly, and these children often show depressive symptoms and reduced quality of life (QOL). We previously developed a smartphone-based self-monitoring app to deliver cognitive behavioral therapy (CBT), implemented it in healthy children, and reported its effectiveness for health promotion.<br> Objective: This study aims to examine the usefulness of the CBT app for improvement in depressive symptoms and QOL in children with mental health disorders.<br> Methods: The participants were 115 children with mental health disorders (eg, school refusal, orthostatic hypotension, eating disorders, developmental disorders, among others) and aged 12‐18 years. The CBT app–based program comprised 1 week of psychoeducation followed by 1 week of self-monitoring. After reading story-like scenarios, participants created a self-monitoring sheet with 5 panels: events, thoughts, feelings, body responses, and actions. All participants received regular mental health care from physicians in addition to the app-based program. To evaluate the participants’ depressive symptoms and QOL, Patient Health Questionnaire for Adolescents (PHQ-9A), Depression Self-Rating Scale for Children (DSRS-C), and Pediatric Quality of Life Inventory (PedsQL) were measured at the beginning of the intervention, and at 2 and 6 months thereafter. Questionnaire for Triage and Assessment with 30 items (QTA30), and Rosenberg Self-Esteem Scale (RSES) were also used to measure their health and self-esteem. Participants were divided into 4 groups on the basis of the PHQ-9A score (above or below the cutoff; PHQ-9A≥5 or PHQ-9A<5) and completion or noncompletion of the CBT app–based program (app [+] or app [-]). The primary outcome was improvement in the DSRS-C score, and secondary outcomes were improvement in other psychometric scales including PedsQL, QTA30, and RSE. A paired-samples t test was used for statistical analysis. The Medical Ethics Committee of Fukuoka University Faculty of Medicine (approval U22-05-002) approved the study design.<br> Results: There were 48, 18, 18, and 7 participants in the PHQ-9A≥5 app (+), PHQ-9A≥5 app (-), PHQ-9A<5 app (+), and PHQ-9A<5 app (-) groups, respectively. A total of 24 participants dropped out. No improvement in the DSRS-C score was observed in all groups. However, PedsQL scores improved significantly at 2 and 6 months in the PHQ-9A<5 app (+) group (t17=6.62; P<.001 and t17=6.11; P<.001, respectively). There was a significant positive correlation between the PHQ-9A scores and the number of self-monitoring sheets completed.<br> Conclusions: The CBT app was useful for improving PedsQL scores of children with mental health disorders. However, a higher-intensity CBT program is necessary for more severely depressed children.<br> Trial Registration: University Hospital Medical Information Network Clinical Trials Registry UMIN000046775; center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053360 No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0169-5002 199 2025 Real-world status of multimodal treatment of Stage IIIA-N2 non-small cell lung cancer in Japan: Results from the SOLUTION study, a non-interventional, multicenter cohort study 108027 EN Hidehito Horinouchi Department of Thoracic Oncology, National Cancer Center Hospital Haruyasu Murakami Department of Thoracic Oncology, Shizuoka Cancer Center Hideyuki Harada Division of Radiation Therapy, Shizuoka Cancer Center Tomotaka Sobue Division of Environmental Medicine and Population Sciences, Graduate School of Medicine, Osaka University Tomohiro Kato Department of Respiratory Medicine, National Hospital Organization Himeji Medical Cente Shinji Atagi Department of Thoracic Oncology, National Hospital Organization Kinki-Chuo Chest Medical Center Toshiyuki Kozuki Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center Takaaki Tokito Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University Hospital Satoshi Oizumi Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center Masahiro Seike Department of Pulmonary Medicine and Oncology, Nippon Medical School Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Tadashi Mio Department of Respiratory Medicine, National Hospital Organization Kyoto Medical Center Takashi Sone Department of Respiratory Medicine, Kanazawa University Hospital Chikako Iwao Department of Medical, AstraZeneca K.K. Takeshi Iwane Department of Medical, AstraZeneca K.K. Ryo Koto Department of Medical, AstraZeneca K.K. Masahiro Tsuboi Department of Thoracic Surgery, National Cancer Center Hospital East Objectives: There is limited consensus on resectability criteria for Stage IIIA-N2 non-small cell lung cancer (NSCLC). We examined the patient characteristics, N2 status, treatment decisions, and clinical outcomes according to the treatment modality for Stage IIIA-N2 NSCLC in Japan.<br> Materials and methods: Patients with Stage IIIA-N2 NSCLC in Japan were consecutively registered in the SOLUTION study between 2013 and 2014. Patients were divided according to treatment (chemoradiotherapy [CRT], surgery + perioperative therapy [neoadjuvant and/or adjuvant therapy], surgery alone). Demographic characteristics, N2 status (number and morphological features), pathological information, and treatments were analyzed descriptively. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) were estimated using the Kaplan–Meier method.<br> Results: Of 227 patients registered, 133 underwent CRT, 56 underwent surgery + perioperative therapy, and 38 underwent surgery alone. The physicians reported the following reasons for unresectability for 116 of 133 CRT patients: large number of metastatic lymph nodes (70.7 %), extranodal infiltration (25.0 %), poor surgical tolerance (19.0 %), or other reasons (18.1 %). CRT was more frequently performed in patients whose lymph nodes had an infiltrative appearance (64.3 %) and was the predominant treatment in patients with multiple involved stations (discrete: 60.0 %; infiltrative: 80.4 %). Distant metastasis with/without local progression was found in 50.4 %, 50.0 %, and 36.8 % of patients in the CRT, surgery + perioperative therapy, and surgery alone groups, respectively. The respective 3-year OS and DFS/PFS rates (median values) were as follows: surgery + perioperative therapy―61.9 % (not reached) and 37.1 % (22.4 months; DFS); CRT group―42.2 % (31.9 months) and 26.8 % (12.0 months; PFS); surgery alone group―37.7 % (26.5 months) and 28.7 % (12.6 months; DFS).<br> Conclusion: This study has illuminated the real-world decision rules for choosing between surgical and non-surgical approaches in patients with Stage IIIA-N2 NSCLC. Our landmark data could support treatment decision making for using immune checkpoint inhibitors and targeted therapy for driver oncogenes in the perioperative therapy era. 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 Survival days of patients with metastatic spinal tumors of lung cancer requiring surgery: a prospective multicenter study 24117 EN Takuya Takahashi Department of Orthopedic Surgery, Institute of Science Tokyo Takashi Hirai Department of Orthopedic Surgery, Institute of Science Tokyo Yuki Shiratani Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University Akinobu Suzuki Department of Orthopaedic Surgery, Osaka Metropolitan University Kenichiro Kakutani Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Satoshi Kato Department of Orthopaedic Surgery Graduate School of Medical Sciences, Kanazawa University Hiroyuki Tominaga Department of Orthopedic Surgery Graduate School of Medical and Dental Sciences, Kagoshima University Hirokazu Inoue Rehabilitation Center, Jichi Medical University Hospital Hirokatsu Sawada Department of Orthopaedic Surgery, Nihon University School of Medicine Norihiko Takegami Department of Orthopaedic Surgery, Mie University Graduate School of Medicine Kazuo Nakanishi Department of Orthopaedic Surgery, Kawasaki Medical School Hideaki Nakajima Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui Masayuki Ishihara Department of Orthopaedic surgery, Kansai Medical University Hospital Tsutomu Oshigiri Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine Toru Funayama Department of Orthopaedic Surgery Institute of Medicine, University of Tsukuba Takuya Iimura Department of Orthopaedic Surgery, Dokkyo Medical University Shinji Tanishima Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University Hiroaki Nakashima Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Daisuke Yamabe Department of Orthopaedic Surgery, Iwate Medical University Ko Hashimoto Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine Koji Uotani Department of Orthopaedic Surgery, Okayama University Hospital Masahiro Funaba Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine Narihito Nagoshi Department of Orthopaedic Surgery, Keio University Kazu Kobayakawa Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University Toshitaka Yoshii Department of Orthopedic Surgery, Institute of Science Tokyo Kazuyuki Watanabe Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine Toshio Nakamae Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Takashi Kaito Department of Orthopedic Surgery, Osaka University Graduate School of Medicine Gen Inoue Department of Orthopaedic Surgery, Kitasato University School of Medicine Shiro Imagama Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Kota Watanabe Department of Orthopaedic Surgery, Keio University Takeo Furuya Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University Surgery for metastatic spinal tumors has improved postoperative activities of daily living. A few studies reported on prognostic factors assessed in large multicenter prospective studies for metastatic spinal tumors of lung cancer origin. This study aimed to determine preoperative prognostic factors in patients undergoing surgery for metastatic spinal tumors associated with lung cancer. This prospective registry study included 74 patients diagnosed and operated with metastatic spine tumors derived from lung cancer in 39 high-volume cancer centers. We examined the postoperative survival period and the preoperative factors related to postoperative survival time. We conducted univariate and multivariate Cox regression analyses to determine preoperative prognostic factors. The mean postoperative survival period was 343 days. Multivariate Cox regression analysis revealed a higher feeding score of vitality index, indications for molecularly targeted therapy, and a higher mobility score of Barthel index as independent factors associated with postoperative survival time in metastatic spinal tumors derived from lung cancer. Patients with indications for molecular-targeted therapy and good vitality exhibited longer survival. These results may help in surgical selection for patients with metastatic spinal tumors derived from lung cancer. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 2192-5682 15 4 2024 Effects of Palliative Surgical Treatment for Spinal Metastases on the Patient’s Quality of Life With a Focus on the Segment of the Metastasis: A Prospective Multicenter Study 2286 2299 EN Naoki Segi Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Hiroaki Nakashima Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Sadayuki Ito Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Jun Ouchida Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Yuki Shiratani Department of Orthopaedic Surgery, Chiba University Hospital Takaki Shimizu Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University Akinobu Suzuki Department of Orthopaedic Surgery, Osaka Metropolitan University Hidetomi Terai Department of Orthopaedic Surgery, Osaka Metropolitan University Kenichiro Kakutani Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Yutaro Kanda Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Hiroyuki Tominaga Department of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Ichiro Kawamura Department of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University Masayuki Ishihara Department of Orthopaedic Surgery, Kansai Medial University Hospital Masaaki Paku Department of Orthopaedic Surgery, Kansai Medial University Hospital Yohei Takahashi Department of Orthopaedic Surgery, Keio University Masahiro Funaba Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine Toru Funayama Department of Orthopaedic Surgery, Institute of Medicine, University of Tsukuba Hideaki Nakajima Department of Orthopaedics and Rehabilitation Medicine, University of Fukui Faculty of Medical Sciences Koji Akeda Department of Orthopaedic Surgery, Mie University Graduate School of Medicine Takashi Hirai Department of Orthopedic Surgery, Tokyo Medical and Dental University Hirokazu Inoue Rehabilitation Center, Jichi Medical University Hospital Kazuo Nakanishi Department of Orthopaedic Surgery, Kawasaki Medical School Haruki Funao Department of Orthopaedic Surgery, International University of Health and Welfare Narita Hospital Tsutomu Oshigiri Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine Bungo Otsuki Department of Orthopaedic Surgery, Kyoto University Hospital Kazu Kobayakawa Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University Shinji Tanishima Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University Ko Hashimoto Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine Takuya Iimura Department of Orthopaedic Surgery, Dokkyo Medical University Hirokatsu Sawada Department of Orthopaedic Surgery, Nihon University School of Medicine Koji Uotani Department of Orthopaedic Surgery, Okayama University Hospital Hiroaki Manabe Department of Orthopedics, Tokushima University Chizuo Iwai Department of Orthopaedic Surgery, Gifu University Hospital Daisuke Yamabe Department of Orthopaedic Surgery, Iwate Medical University Akihiko Hiyama Department of Orthopaedic Surgery, Tokai University School of Medicine Shoji Seki Department of Orthopaedic Surgery, University of Toyama Yuta Goto Department of Orthopaedic Surgery, Nagoya City University Masashi Miyazaki Department of Orthopaedic Surgery, Faculty of Medicine, Oita University Kazuyuki Watanabe Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine Toshio Nakamae Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Takashi Kaito Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine Narihito Nagoshi Department of Orthopaedic Surgery, Keio University Satoshi Kato Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University Kota Watanabe Department of Orthopaedic Surgery, Keio University Shiro Imagama Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Gen Inoue Department of Orthopaedic Surgery, Kitasato University School of Medicine Takeo Furuya Department of Orthopaedic Surgery, Chiba University Hospital Study Design: Prospective multicenter study.<br> Objectives: Palliative surgery is crucial for maintaining the quality of life (QOL) in patients with spinal metastases. This study aimed to compare the short-term outcomes of QOL after palliative surgery between patients with metastatic spinal tumors at different segments.<br> Methods: We prospectively compared the data of 203 patients with spinal metastases at 2-3 consecutive segments who were divided into the following three groups: cervical, patients with cervical spine lesions; thoracic, patients with upper–middle thoracic spine lesions; and TL/L/S, patients with lesions at the thoracolumbar junction and lumbar and sacral regions. Preoperative and postoperative EuroQol 5-dimension (EQ5D) 5-level were compared.<br> Results: All groups exhibited improvement in the Frankel grade, performance status, pain, Barthel index, EQ5D health state utility value (HSUV), and EQ5D visual analog scale (VAS) postoperatively. Although preoperative EQ5D HSUVs did not significantly differ between the groups (cervical, 0.461 ± 0.291; thoracic, 0.321 ± 0.292; and TL/L/S, 0.376 ± 0.272), the thoracic group exhibited significantly lower postoperative EQ5D HSUVs than the other two groups (cervical, 0.653 ± 0.233; thoracic, 0.513 ± 0.252; and TL/L/S, 0.624 ± 0.232). However, postoperative EQ5D VAS was not significantly different between the groups (cervical, 63.4 ± 25.8; thoracic, 54.7 ± 24.5; and TL/L/S, 61.7 ± 21.9).<br> Conclusions: Palliative surgery for metastatic spinal tumors provided comparable QOL improvement, irrespective of the spinal segment involved. Patients with upper and middle thoracic spinal metastases had poorer QOL outcomes than those with metastases in other segments; however, sufficient QOL improvement was achieved. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1099-5129 27 2 2025 SCN5A variant type-dependent risk prediction in Brugada syndrome euaf024 EN Takanori Aizawa Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine Takeru Makiyama Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine Hai Huang Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine , 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 , Tomohiko Imamura Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine Megumi Fukuyama Department of Cardiovascular Medicine, Shiga University of Medical Science Keiko Sonoda Medical Genome Center, National Cerebral and Cardiovascular Center Koichi Kato Department of Cardiovascular Medicine, Shiga University of Medical Science Takashi Hisamatsu Department of Public Health, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Yuko Nakamura Department of Pediatrics, Tsuchiura Kyodo General Hospital Kenji Hoshino Department of Cardiology, Saitama Children’s Medical Center Junichi Ozawa Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences Hiroshi Suzuki Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital Kazushi Yasuda Department of Pediatric Cardiology, Aichi Children’s Health and Medical Center Hisaaki Aoki Department of Pediatric Cardiology, Osaka Women’s and Children’s Hospital Takashi Kurita Division of Cardiovascular Center, Kindai University School of Medicine Yoko Yoshida Division of Pediatric Cardiology and Electrophysiology, Osaka City General Hospital Tsugutoshi Suzuki Division of Pediatric Cardiology and Electrophysiology, Osaka City General Hospital Yoshihide Nakamura Division of Pediatric Cardiology and Electrophysiology, Osaka City General Hospital Yoshiharu Ogawa Division of Cardiology, Hyogo Prefectural Kobe Children’s Hospital Shintaro Yamagami Department of Cardiology, Tenri Hospital Hiroshi Morita Department of Cardiovascular Therapeutics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinsuke Yuasa Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Masakazu Fukuda Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine Makoto Ono Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine Hidekazu Kondo Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University Naohiko Takahashi Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University Seiko Ohno Medical Genome Center, National Cerebral and Cardiovascular Center Yoshihisa Nakagawa Department of Cardiovascular Medicine, Shiga University of Medical Science Koh Ono Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine Minoru Horie Department of Cardiovascular Medicine, Shiga University of Medical Science Aims The variant in SCN5A with the loss of function (LOF) effect in the cardiac Na+ channel (Nav1.5) is the definitive cause for Brugada syndrome (BrS), and the functional analysis data revealed that LOF variants are associated with poor prognosis. However, which variant types (e.g. missense or non-missense) affect the prognoses of those variant carriers remain unelucidated.<br> Methods and results We defined SCN5A LOF variants as all non-missense and missense variants that produce peak INa < 65% of wild-type previously confirmed by patch-clamp studies. The study population consisted of 76 Japanese BrS patients (74% patients were male and the median age [IQR] at diagnosis was 28 [14–45] years) with LOF type of SCN5A variants: 40 with missense and 36 with non-missense variants. Non-missense variant carriers presented significantly more severe cardiac conduction disorder compared to the missense variant carriers. During follow-up periods of 9.0 [5.0–14.0] years, compared to missense variants, non-missense variants were significant risk factors of lifetime lethal arrhythmia events (LAEs) (P = 0.023). When focusing only on the missense variants that produce no peak INa, these missense variant carriers exhibited the same clinical outcomes as those with non-missense (log-rank P = 0.325). After diagnosis, however, both variant types were comparable in risk of LAEs (P = 0.155).<br> Conclusion We identified, for the first time, that SCN5A non-missense variants were associated with higher probability of LAE than missense variants in BrS patients though it did not change significantly after diagnosis. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1554-8929 19 12 2024 Discovery of a Compound That Inhibits IRE1α S-Nitrosylation and Preserves the Endoplasmic Reticulum Stress Response under Nitrosative Stress 2429 2437 EN Haruna Kurogi Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nobumasa Takasugi Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sho Kubota Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ashutosh Kumar Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN Takehiro Suzuki Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science Naoshi Dohmae Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science Daisuke Sawada Department of Fine Organic Synthesis, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kam Y.J. Zhang Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN Takashi Uehara Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Inositol-requiring enzyme 1α (IRE1α) is a sensor of endoplasmic reticulum (ER) stress and drives ER stress response pathways. Activated IRE1α exhibits RNase activity and cleaves mRNA encoding X-box binding protein 1, a transcription factor that induces the expression of genes that maintain ER proteostasis for cell survival. Previously, we showed that IRE1α undergoes S-nitrosylation, a post-translational modification induced by nitric oxide (NO), resulting in reduced RNase activity. Therefore, S-nitrosylation of IRE1α compromises the response to ER stress, making cells more vulnerable. We conducted virtual screening and cell-based validation experiments to identify compounds that inhibit the S-nitrosylation of IRE1α by targeting nitrosylated cysteine residues. We ultimately identified a compound (1ACTA) that selectively inhibits the S-nitrosylation of IRE1α and prevents the NO-induced reduction of RNase activity. Furthermore, 1ACTA reduces the rate of NO-induced cell death. Our research identified S-nitrosylation as a novel target for drug development for IRE1α and provides a suitable screening strategy. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 1936-8798 18 9 2025 Novel Technique for Implanting the Second Valve Accompanied by Simultaneous Snorkel Stenting 1203 1205 EN Hironobu Toda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Ueki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Hara Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Miki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Takaya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Morimitsu Division of Radiological Technology, Okayama University Hospital Hiroshi Morita Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2772-3747 5 1 2025 Evaluating Pericoronary Adipose Tissue Attenuation to Predict Cardiovascular Events 1 11 EN Takahiro Nishihara Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Miyoshi Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kentaro Ejiri Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Osawa Department of General Internal Medicine 3, Kawasaki Medical School General Medicine Center Soichiro Fuke Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital Kousuke Seiyama Department of Cardiology, Kagawa Prefectural Central Hospital Masayuki Doi Department of Cardiology, Kagawa Prefectural Central Hospital Mitsutaka Nakashima Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Miki Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinsuke Yuasa Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Pericoronary adipose tissue attenuation (PCATA) is a novel imaging biomarker of pericoronary inflammation associated with coronary artery disease. Several studies have reported the usefulness of PCATA among people of European ethnicity; however, data are lacking concerning those of Asian ethnicity.<br> Objectives: This multicenter study aimed to evaluate the effect of PCATA on prognosis in East Asian patients.<br> Methods: Between August 2011 and December 2016, 2,172 patients underwent clinically indicated coronary computed tomography angiography (CTA) at 4 hospitals in Japan. Among them, 1,270 patients were analyzed. PCATA was evaluated using coronary CTA to measure pericoronary adipose tissue density surrounding the 3 major coronary arteries. The outcomes were composite cardiovascular events, including cardiovascular death and acute coronary syndrome; 33 cardiovascular events observed during a median follow-up of 6.0 years (Q1-Q3: 3.6-8.2 years).<br> Results: Right coronary artery (RCA)-PCATA was significantly higher in patients with cardiovascular events than in those without (−63.7 ± 8.9 HU vs −67.4 ± 9.1 HU, respectively; P = 0.021). High RCA-PCATA was significantly associated with cardiovascular events in a model that included the Hisayama risk score and adverse coronary CTA findings (HR: 1.55; 95% CI: 1.07-2.24; P = 0.019).<br> Conclusions: High RCA-PCATA showed significant association with future cardiovascular events after adjusting conventional risk factors and adverse coronary CTA findings in East Asian patients who underwent clinically indicated coronary CTA. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 0094-8276 52 14 2025 Unraveling the Complex Features of the Seismic Scatterers in the Mid‐Lower Mantle Through Phase Transition of (Al, H)‐Bearing Stishovite e2024GL114146 EN Yingxin Yu Deep Space Exploration Laboratory, School of Earth and Space Sciences, University of Science and Technology of China Youyue Zhang Institute for Planetary Materials, Okayama University Luo Li Deep Space Exploration Laboratory, School of Earth and Space Sciences, University of Science and Technology of China Xinyue Zhang Deep Space Exploration Laboratory, School of Earth and Space Sciences, University of Science and Technology of China Denglei Wang Deep Space Exploration Laboratory, School of Earth and Space Sciences, University of Science and Technology of China Zhu Mao Deep Space Exploration Laboratory, School of Earth and Space Sciences, University of Science and Technology of China Ningyu Sun Deep Space Exploration Laboratory, School of Earth and Space Sciences, University of Science and Technology of China Yanyao Zhang Earth and Planetary Sciences, Stanford University Xinyang Li State Key Laboratory of High Pressure and Superhard Materials, College of Physics, Jilin University Wancai Li CAS Key Laboratory of Crust‐Mantle Materials and Environments, School of Earth and Space Sciences, University of Science and Technology of China Sergio Speziale GFZ German Research Centre for Geosciences Dongzhou Zhang GeoSoilEnviroCARS, University of Chicago Jung‐Fu Lin Department of Earth and Planetary Sciences, Jackson School of Geosciences, The University of Texas at Austin Takashi Yoshino Institute for Planetary Materials, Okayama University Small-scale scatterers observed in the mid-lower mantle beneath the subduction zones are thought to result from the phase transition of stishovite within subducted oceanic crusts. Here we investigate the phase transition of (Al, H)-bearing stishovite with four compositions at simultaneously high P-T conditions combining Raman spectroscopy and X-ray diffraction. These experimental results reveal that the incorporation of 0.01 a.p.f.u Al into stishovite with H/Al ratio of ∼1/3 lowers the transition pressure by 6.7(3) GPa. However, the Clapeyron slope of this transition is nearly unaffected by changes in the Al content and has a value of 12.2–12.5(3) MPa/K. According to our results, Al content variation ranging from 0 to 0.07 a.p.f.u in SiO2 can reasonably explain the depth distribution from 800 to 1,900 km of the seismic scatterers observed in the circum-Pacific region. These results deepen our understanding on the complex features of mid-lower mantle seismic scatterers and corresponding dynamic processes. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1040-4651 37 7 2025 Pancentromere analysis of Allium species reveals diverse centromere positions in onion and gigantic centromeres in garlic koaf142 EN Kiyotaka Nagaki Institute of Plant Science and Resources, Okayama University Koichiro Ushijima Graduate School of Environmental and Life Science, Okayama University Takashi Akagi Graduate School of Environmental and Life Science, Okayama University Keisuke Tanaka NODAI Genome Research Center, Tokyo University of Agriculture Hisato Kobayashi NODAI Genome Research Center, Tokyo University of Agriculture In eukaryotes, centromeres interact with the kinetochore for distribution of genetic information in cell division, yet their sequence and size are diverse among species. However, their position on chromosomes is considered to be conserved within a species. In this study, we analyzed the centromeres of 3 Allium species, namely, Welsh onion (Allium fistulosum), onion (Allium cepa), and garlic (Allium sativum) via pancentromere analysis and repetitive sequence analysis of centromeres and their neighborhoods and revealed their mobility, sequence organization, and size. Among the 3 species, Welsh onion and garlic had stable centromeres, but the onion centromere appeared to be polymorphic and frequently differed in position by up to 28.0 Mb among cultivars and between multiple individuals of the same cultivar. This mobility was stabilized by hybridization with Welsh onions. Furthermore, these 3 species have very different centromere sequence organization, including differences in the existence and maturity of centromeric satellites, and differences in centromere size, with Welsh onion having a centromere of 1.9 Mb, and garlic having a centromere of ∼10.6 Mb, the largest of any organism with monocentric chromosomes analyzed to date. Our pancentromere analysis of these Allium species reveals the variation in sequence organization, size, and position of this important chromosomal region. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0753-3322 186 2025 (+)-Terrein exerts anti-obesity and anti-diabetic effects by regulating the differentiation and thermogenesis of brown adipocytes in mice fed a high-fat diet 118030 EN Haruka Aoki-Saito Department of Allergy and Respiratory Medicine, Gunma University Graduate School of Medicine Hiroki Mandai Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science Takashi Nakakura Department of Anatomy, Teikyo University School of Medicine Tsutomu Sasaki Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University Tadahiro Kitamura Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University Kazuhiro Omori Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takeshi Hisada Gunma University Graduate School of Health Sciences Shuichi Okada Department of Diabetes, Soleiyu Asahi Clinic Seiji Suga Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University Masanobu Yamada Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine Tsugumichi Saito Department of Health & Sports Sciences, Faculty of Education, Tokyo Gakugei University Objective: (+)-Terrein, a low-molecular-weight secondary metabolite from Aspergillus terreus, inhibits adipocyte differentiation in vitro. However, the precise mechanisms underlying the effects of (+)-terrein on adipocytes remain unclear. We hypothesized that (+)-terrein modulates adipogenesis and glucose homeostasis in obesity and diabetes via anti-inflammatory action and regulation of adipocyte differentiation. Hence, in this study, we aimed to investigate the in vivo anti-diabetic and anti-obesity effects of (+)-terrein.<br> Methods: Male C57BL/6 J mice were fed normal chow or high-fat (HF) diet and administered (+)-terrein (180 mg/kg) via intraperitoneal injection. Glucose and insulin tolerance tests, serum biochemical assays, and histological analyses were also performed. Rat brown preadipocytes, mouse brown preadipocytes (T37i cells), and inguinal white adipose tissue (ingWAT) preadipocytes were exposed to (+)-terrein during in vitro adipocyte differentiation. Molecular markers associated with thermogenesis and differentiation were quantified using real-time polymerase chain reaction and western blotting.<br> Results: (+)-Terrein-treated mice exhibited improved insulin sensitivity and reduced serum lipid and glucose levels, irrespective of the diet. Furthermore, (+)-terrein suppressed body weight gain and mitigated fat accumulation by activating brown adipose tissue in HF-fed mice. (+)-Terrein facilitated the in vitro differentiation of rat brown preadipocytes, T37i cells, and ingWAT preadipocytes by upregulating peroxisome proliferator-activated receptor-γ (PPARγ). This effect was synergistic with that of a PPARγ agonist.<br> Conclusion: This study demonstrated that (+)-terrein effectively induces PPARγ expression and brown adipocyte differentiation, leading to reduced weight gain and improved glucose and lipid profiles in HF-fed mice. Thus, (+)-terrein is a potent novel agent with potential anti-obesity and anti-diabetic properties. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 0039-9140 297 2026 Microfluidic paper-based analytical devices for antioxidant vitamins C and E in foods 128540 EN Mana Kawahara Department of Chemistry, Okayama University Kaewta Danchana Department of Chemistry, Okayama University Takashi Kaneta Department of Chemistry, Okayama University In this study, we developed microfluidic paper-based analytical devices (μPADs) for the determination of antioxidant vitamins. The proposed μPADs utilize the reduction of metal ions by hydrophilic and hydrophobic antioxidant vitamins, which is followed by colorimetric reactions with chelating reagents. Hydrophilic vitamin C reduces Fe(III) to Fe(II) and forms a stable Fe(II)-bathophenanthroline complex in an aqueous solution. By contrast, this complex is unstable in organic solvents, and hydrophobic vitamin E requires Fe(III) and bathophenanthroline to be replaced with Cu(II) and bathocuproine. In these results, the relationship between the logarithm of a vitamin's concentration and its color intensity was linear and ranged from 4.4 to 35 mg L−1 for ascorbic acid and 50–200 mg L−1 for α-tocopherol. The limits of detection, estimated from the standard deviation of blank samples, were 3.1 mg L−1 for ascorbic acid and either 27 mg L−1 (in hexane) or 48 mg L−1 (in ethanol) for α-tocopherol. The proposed method was used to quantify vitamin C in bell peppers, mandarin oranges, kiwifruit, and lemons, as well as vitamin E in almonds, almond milk, and dietary supplements. The results demonstrate the effectiveness of these μPADs for the practical analysis of antioxidant vitamins in food samples. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 2772-4174 13 2025 Photochemical internalization of mRNA using a photosensitizer and nucleic acid carriers 100242 EN Hayaki Maemoto Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ryohei Suzaki Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kazunori Watanabe Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Keiji Itaka Department of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University Takashi Ohtsuki Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University mRNA has great potential for therapeutic applications because it can encode a variety of proteins and antigens, in addition to advantages over DNA in terms of gene expression without genomic integration, nuclear localization, or transcription. However, therapeutic applications of mRNA require safe and effective delivery into target cells. Therefore, we aimed to investigate photochemical internalization (PCI) as a promising strategy for delivering mRNA to target cells. In this strategy, mRNA is taken up into cells by endocytosis, accumulates in endosomes, and is released in a light-dependent manner from the endosomes using an endosome-accumulating photosensitizer, aluminum phthalocyanine disulfonate (AlPcS2a), in combination with nucleic acid carrier molecules. We compared the efficacy of various nucleic acid carriers, including branched polyethyleneimine (bPEI) and poly{N'-[N-(2-aminoethyl)-2-aminoethyl] aspartamide} (PAsp(DET)) under the same conditions for PCI-based mRNA delivery. Our results indicated that bPEI and PAsp(DET) at low N/P ratios exhibited efficient light-enhancement of mRNA expression by PCI with AlPcS2a. Notably, bPEI exhibited the highest light-dependent mRNA delivery among the carriers evaluated (including cationic polymers, cationic peptides, and lipids), whereas PAsp(DET) showed promise for clinical use because of its lower toxicity compared with bPEI. This PCI strategy allows effective cytosolic mRNA delivery at low N/P ratios, thereby reducing cationic carrier molecule-induced cytotoxicity. This method allows spatiotemporal control of protein expression and holds potential for novel light-dependent mRNA therapies. Overall, this study provided valuable insights into optimizing mRNA delivery systems for therapeutic applications. No potential conflict of interest relevant to this article was reported.

Japanese Circulation Society Acta Medica Okayama 1346-9843 89 7 2025 Hemodynamic Changes After Wire Frame Occluders vs. Metal Mesh Devices for Atrial Septal Defect 930 938 EN Mitsutaka Nakashima Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Takaya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Miki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Nakayama Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Nakagawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Teiji Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Transcatheter atrial septal defect (ASD) closure is the first treatment option for secundum ASD, but parameters for optimal device selection have not been established. We compared outcomes between occluders with a wire frame and metal mesh devices.<br> Methods and Results: This study included secundum ASD patients implanted with a wire frame occluder (GORE®CARDIOFORM ASD occluder [GCA]; W.L. Gore & Associates) or metal mesh devices (Amplatzer septal occluder device [Abbott] and Occlutech Figulla Flex II device [Occlutech]). The presence of residual shunt and B-type natriuretic peptide (BNP) levels after implantation were compared. Of the 970 patients with either GCA (n=48) or a metal mesh device (n=922; control), 42 patients from each group were analyzed after propensity score matching. The prevalence of residual shunt was significantly lower in the GCA group 1 day and 1 month after implantation (P<0.001 and P=0.017, respectively), whereas there was no significant difference between the 2 groups 6 months later (P=0.088). BNP levels at 1 month were significantly higher in the GCA group (ratio of change 1.36; 95% confidence interval [CI] 1.01–1.83), but did not differ significantly between the 2 groups at 6 months (ratio of change 1.04; 95% CI 0.65–1.65).<br> Conclusions: Patients implanted with a wire frame occluder had a lower prevalence of residual shunt and a greater increase in BNP levels in the early period after implantation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1868-4300 2025 Efficacy of transcatheter patent foramen ovale closure for drug-resistant migraine: initial experience in Japan and long-term outcome EN Teiji Akagi Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoichi Takaya Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Miki Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Rie Nakayama Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Nakagawa Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mitsuki Nakashima Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiaki Takahashi Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinsuke Yuasa Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University This study evaluates the efficacy and safety of transcatheter patent foramen ovale (PFO) closure for the treatment of drug-resistant migraine in Japan. Previous studies have suggested a potential benefit for migraine with aura, although large-scale trials in the United States and Europe have failed to confirm efficacy as a primary endpoint. The study included 27 patients (mean age 36.4 years, 15 female, 21 with aura) who had more than two migraine attacks per month despite medication. All had PFO confirmed by transesophageal echocardiography and underwent transcatheter closure with the Amplatzer PFO Occluder. Patients were followed up to 12 months with migraine severity monitored by headache specialist. The procedure was successful and without complications in all cases. One patient required a larger occluder (35 mm) due to the size of PFO. At 12 months, 22 of 27 (81%) patients reported either complete resolution or improvement of migraine. Specifically, 10 of 21 (48%) patients with aura experienced complete resolution of migraine at one year. Patients without aura had a lower response rate, with only one case of complete resolution. Despite limitations such as the lack of a control group and potential patient selection bias, the study demonstrated that PFO closure may provide significant relief for patients with drug-resistant migraine, particularly those with aura. These findings support further investigation to better define its clinical indications and potential benefits. No potential conflict of interest relevant to this article was reported.

IEEE Acta Medica Okayama 2833-2350 2023 Non Real-Time Data Transmission Performance Analysis of PROFINET for Assuring Data Transmission Quality 236 244 EN Takashi Norimatsu Graduate School of Natural Science and Technology, Okayama University Toshihiro Yamauchi Faculty of Environmental, Life, Natural Science and Technology, Okayama University The industrial Ethernet PROFINET supports three different data transmission modes: isochronous real-time (IRT), real-time (RT), and non real-time (NRT) transmitting data requiring hard, soft, and no real-time performances, respectively. The data transmission latency in the NRT increased with the amount of data transmission in the IRT, RT, and NRT. Therefore, the quality of data transmission in NRT may degrade as the amount of data transmission in IRT, RT, and NRT increases. In this study, we derived the average data transmission latency in an NRT with data transmission in IRT and RT by applying stochastic processes. This allowed us to maintain the quality of data transmission in the NRT by adjusting the number of devices connected to the network and the number of applications transmitting data in the NRT so that the average latency of data in the NRT does not exceed a certain value. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 64 5 2025 A Novel De Novo Variant in KCNH5 in a Patient with Refractory Epileptic Encephalopathy 759 762 EN Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Tatsuhiko Naito 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 Jun Mitsui Department of Neurology, Graduate School of Medicine, The University of Tokyo Hiroaki Harada Department of Rheumatology and Allergy, Graduate School of Medicine, The University of Tokyo Keishi Fujio Department of Rheumatology and Allergy, Graduate School of Medicine, The University of Tokyo Jun Fujishiro Department of Pediatric Surgery, Graduate School of Medicine, The University of Tokyo Harushi Mori Department of Radiology, School of Medicine, Jichi Medical University Shinichi Morishita Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo Shoji Tsuji Department of Neurology, Graduate School of Medicine, The University of Tokyo Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo We herein report a novel de novo KCNH5 variant in a patient with refractory epileptic encephalopathy. The patient exhibited seizures at 1 year and 7 months old, which gradually worsened, leading to a bedridden status. Brain magnetic resonance imaging (MRI) showed cerebral atrophy and cerebellar hypoplasia. A trio whole-exome sequence analysis identified a de novo heterozygous c.640A>C, p.Lys214Gln variant in KCNH5 that was predicted to be deleterious. Recent studies have linked KCNH5 to various epileptic encephalopathies, with many patients showing normal MRI findings. The present case expands the clinical spectrum of the disease, as it is characterized by severe neurological prognosis, cerebral atrophy, and cerebellar hypoplasia. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2054-345X 12 1 2025 In-frame deletion variant of ABCD1 in a sporadic case of adrenoleukodystrophy 5 EN Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Atsushi Sudo Department of Neurology, Graduate School of Medicine, The University of Tokyo Toshiyuki Kakumoto Department of Neurology, Graduate School of Medicine, The University of Tokyo Akihito Hao Department of Neurology, Graduate School of Medicine, The University of Tokyo Mitsuhiro Kainaga Department of Neurology, Graduate School of Medicine, The University of Tokyo Hyangri Chang Department of Neurology, Graduate School of Medicine, The University of Tokyo Tatsuo Mano Department of Neurology, Graduate School of Medicine, The University of Tokyo Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Mitsui Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Toshihiro Hayashi Department of Neurology, Graduate School of Medicine, The University of Tokyo Shinichi Morishita Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo Shoji Tsuji Department of Neurology, Graduate School of Medicine, The University of Tokyo Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Adrenoleukodystrophy (ALD), an X-linked leukodystrophy caused by pathogenic variants in ABCD1, exhibits a broad range of phenotypes from childhood-onset cerebral forms to adult-onset adrenomyeloneuropathy (AMN). We report a rare in-frame ABCD1 deletion c.1469_71delTGG (p.Val490del) in a man with AMN. Although this variant has been interpreted as ‘uncertain significance’ in ClinVar, biochemical analysis along with clinical evaluation confirmed the pathogenicity of this variant, underscoring the importance of functional assessment of in-frame deletions. No potential conflict of interest relevant to this article was reported.

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

Acta Medica Okayama 2025 A Study on Information Security for End-to-End Communication by TCP/IP Internet Protocol Suite EN Takashi NORIMATSU Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 CD106 in Tumor-Specific Exhausted CD8+ T Cells Mediates Immunosuppression by Inhibiting TCR Signaling EN Yuto NAOI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1472-6831 25 1 2025 Exploring the relationship between posture-dependent airway assessment in orthodontics: insights from kinetic MRI, cephalometric data, and three-dimensional MRI analysis 745 EN Naoki Oka Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Janvier Habumugisha Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiro Nakamura Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoki Kataoka Division of Oral and Maxillofacial Surgery, Tottori University Atsuro Fujisawa Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Noriaki Kawanabe Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Izawa Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Kamioka Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Previous studies have assessed the upper airway using various examination methods, such as cephalometric imaging and magnetic resonance imaging (MRI). However, there is a significant gap in the research regarding the relationship between these different imaging modalities. This study compares airway assessments using kinetic MRI and cephalometric scans, examining their correlation with three dimensional (3D) MRI data.<br> Materials and methods Kinetic MRI, cephalometric scans, and 3D MRI of forty-seven participants were used in the present study. Airway areas and widths were measured at the retropalatal, retroglossal, and hypopharyngeal levels in both kinetic MRI and cephalometric scans. Airway volumes were calculated from 3D MRI data. Statistical analyses, including the Wilcoxon Signed Rank test, Spearman correlation, and multiple linear regression, were performed to evaluate the data and identify significant differences, correlations, and prediction models, respectively.<br> Results Significant differences were found between kinetic MRI and cephalometric scans. Cephalometric data showed larger airway areas and widths compared to kinetic MRI measurements. Although both cephalometric and kinetic MRI showed a correlation with 3D MRI, kinetic MRI demonstrated stronger correlations with 3D MRI airway volumes than cephalometric scans. According to our linear regression model equations, RPA-Max (maximum retropalatal airway area) and RPA (retropalatal airway area) can elucidate variations in RPV (retropalatal airway volume). RGA-Med (median retroglossal airway area) and RGA-Min (minimum retroglossal airway area) can explain variations in RGV (retroglossal airway volume). HPA (hypopharyngeal airway area) and ULHPAW-Max (maximum upper limit hypopharyngeal airway width) account for variations in HPV (hypopharyngeal airway volume). Additionally, TA-Max (maximum total airway area) can account for variations in TPV (total pharyngeal airway volume).ConclusionBoth cephalometric data and kinetic MRI data showed correlations with 3D MRI data. The shared posture of kinetic MRI and 3D MRI led to stronger correlations between these two modalities. Although cephalometric data had fewer correlations with 3D MRI and predictors for 3D airway volume, they were still significant. Our study highlights the complementary nature of kinetic MRI and cephalometric imaging, as both provide valuable information for airway assessment and exhibit significant correlations with 3D MRI data. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0039-9140 295 2025 Using a microfluidic paper-based analytical device and solid-phase extraction to determine phosphate concentration 128303 EN Kaewta Danchana Department of Chemistry, Okayama University Haruka Namba Department of Chemistry, Okayama University Takashi Kaneta Department of Chemistry, Okayama University Phosphate is an essential nutrient, but in high concentrations it contributes to water pollution. Traditional methods for phosphate measurement, such as absorption spectrophotometry and ion chromatography, require expensive equipment and skilled operators. This study introduces a microfluidic paper-based analytical device (μPAD) that is designed to accomplish field-based, low-concentration phosphate measurements. This μPAD utilizes colorimetric detection based on the molybdenum blue method. Herein, we describe how the conditions were optimized in terms of design and sensitivity by adjusting reagent concentrations, paper thickness, and the time frames for sample introduction, and reaction. The operation consists of simply dipping the μPAD into a sample, capturing images in a home-made photo studio box, and processing the images with ImageJ software to measure RGB intensity. An additional preconcentration step involves solid-phase extraction with an anion exchange resin that achieves a 10-fold enrichment, which enables detection that ranges from 0.05 to 1 mg L−1 with a detection limit of 0.089 mg L−1 and a quantification limit of 0.269 mg L−1. The replicated measurements showed good reproducibility both intraday and interday (five different days) as 4.7 % and 3.0 % of relative standard deviations, respectively. After storage in a refrigerator for as long as 26 days, this μPAD delivered stable and accurate results for real-world samples of natural water, soil, and toothpaste. The results produced using this system correlate well with those produced via spectrophotometry. This μPAD-based method is a cost-effective, portable, rapid, and simple approach that allows relatively unskilled operators to monitor phosphate concentrations in field applications. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 3 2025 Continuous Stimulation with Glycolaldehyde-derived Advanced Glycation End Product Reduces Aggrecan and COL2A1 Production via RAGE in Human OUMS-27 Chondrosarcoma Cells 157 166 EN Omer Faruk Hatipoglu Department of Pharmacology, Faculty of Medicine, Kindai University Takashi Nishinaka Department of Pharmacology, Faculty of Medicine, Kindai University Kursat Oguz Yaykasli Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen Shuji Mori Department of Pharmacology, School of Pharmacy, Shujitsu University Masahiro Watanabe Department of Pharmacology, School of Pharmacy, Shujitsu University Takao Toyomura Department of Pharmacology, School of Pharmacy, Shujitsu University Masahiro Nishibori Department of Translational Research & Dug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Hirohata Department of Medical Technology, Graduate School of Health Sciences, Okayama University Hideo Takahashi Department of Pharmacology, Faculty of Medicine, Kindai University Hidenori Wake Department of Pharmacology, Faculty of Medicine, Kindai University Original Article 10.18926/AMO/68723 Chondrocytes are responsible for the production of extracellular matrix (ECM) components such as collagen type II alpha-1 (COL2A1) and aggrecan, which are loosely distributed in articular cartilage. Chondrocyte dysfunction has been implicated in the pathogenesis of rheumatic diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). With age, advanced glycation end products (AGEs) accumulate in all tissues and body fluids, including cartilage and synovial fluid, causing and accelerating pathological changes associated with chronic diseases such as OA. Glycolaldehyde-derived AGE (AGE3), which is toxic to a variety of cell types, have a stronger effect on cartilage compared with other AGEs. To understand the long-term effects of AGE3 on cartilage, we stimulated a human chondrosarcoma cell line (OUMS-27), which exhibits a chondrocytic phenotype, with 10 μg/ml AGE3 for 4 weeks. As a result, the expressions of COL2A1 and aggrecan were significantly downregulated in the OUMS-27 cells without inducing cell death, but the expressions of proteases that play an important role in cartilage destruction were not affected. Inhibition of the receptor for advanced glycation end products (RAGE) suppressed the AGE3-induced reduction in cartilage component production, suggesting the involvement of RAGE in the action of AGE3. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2772-963X 4 5 2025 Prognostic Value of Pericoronary Fat Attenuation Index on Computed Tomography for Hospitalization for Heart Failure 101685 EN Mitsutaka Nakashima Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Nishihara Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Miki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Hara Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Takaya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Nakayama Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keishi Ichikawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Osawa Department of General Internal Medicine 3, Kawasaki Medical School General Medicine Centre Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences BACKGROUND Pericoronary fat attenuation index (FAI) assessed on computed tomography is associated with the inflammation of the pericoronary artery. <br> OBJECTIVES This study aimed to investigate whether pericoronary FAI predicts hospitalization for heart failure with preserved ejection fraction (HFpEF). <br> METHODS This retrospective single-center study included 1,196 consecutive patients who underwent clinically indicated coronary computed tomography angiography (CCTA) and transthoracic echocardiography. We assessed the FAI of proximal 40-mm segments for each major epicardial coronary vessel. The primary outcome was the incidence of hospitalization for HFpEF. Patients were divided into groups based on the optimal cutoff value for predicting hospitalization for HFpEF by receiver operating characteristic curve analysis. <br> RESULTS During a median follow-up of 4.3 years, 29 hospitalizations for HFpEF occurred. Multivariable Cox regression analysis revealed that a left anterior descending artery (LAD)-FAI >=-63.4 HU and a left circumflex artery-FAI >=-61.6 HU were significantly associated with hospitalization for HF after adjustment for age and sex (HR: 4.8; 95% CI: 2.1-10.8 and HR: 4.5; 95% CI: 2.1-9.4, respectively). The addition of LAD-FAI >-63.4 HU to a model incorporating other risk factors, including hypertension, estimated glomerular filtration rate <60 mL/min/1.73 m2, and significant stenosis on CCTA, increased the C-statistic for predicting hospitalization for HFpEF from 0.646 to 0.750 (P = 0.010). <br> CONCLUSIONS LAD-and left circumflex artery-FAI can predict hospitalization for HFpEF in patients undergoing clinically indicated CCTA. Pericoronary inflammation may be useful for identifying patients at high risk of developing HFpEF. No potential conflict of interest relevant to this article was reported.

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

Optica Publishing Group Acta Medica Okayama 1094-4087 33 8 2025 Demonstration of enhanced Raman scattering in high-Q silicon nanocavities operating below the silicon band-gap wavelength 18515 18529 EN Yu Shimomura Department of Physics and Electronics, Osaka Metropolitan University Takashi Asano Department of Electronic Science and Engineering, Kyoto University Ayumi Ishihara Department of Physics and Electronics, Osaka Metropolitan University Susumu Noda Department of Electronic Science and Engineering, Kyoto University Yasushi Takahashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University We experimentally determined the quality factor (Q) and the intensity of the Raman scattered light for different silicon photonic-crystal nanocavities operating at wavelengths shorter than the silicon band-gap wavelength. Despite the relatively large absorption of silicon in this wavelength region, we observed Q values greater than 10,000 for cavities with a resonance wavelength of 1.05 mu m, and Q values greater than 30,000 for cavities with a resonance wavelength of 1.10 mu m. Additionally, we measured the Raman scattering spectra of cavities with resonance wavelengths of 1.10 mu m and 1.21 mu m. On average, the generation efficiency of the Raman scattered light in a 1.10-mu m nanocavity is 6.5 times higher than that in a 1.21-mu m nanocavity. These findings suggest that silicon nanocavities operating below the silicon band-gap wavelength could be useful in the development of silicon-based light sources. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 137 1 2025 若手・中堅耳鼻咽喉科医師の臨床研究に対する質問紙調査 20 24 EN Kensuke Uraguchi Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soshi Takao Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akiko Sugaya Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mizuo Ando Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 　Introduction : Clinical research is crucial for the advancement of medicine, but modern otolaryngologists' attitudes regarding clinical research have not been known. This study was conducted to survey the background, knowledge, and interest in clinical research among junior and mid-career otolaryngologists.<br> 　Methods : A questionnaire survey was distributed to 34 otolaryngologists with ≤15 years' clinical experience working at Okayama University and its affiliated facilities. The respondents were divided into junior (non-specialists) and mid-career otolaryngologists (specialists) based on whether they were board-certified otolaryngologists. The survey assessed their background, understanding, and interest in clinical research.<br> 　Results : Twenty-nine otolaryngologists (83%) responded (10 junior and 19 mid-career otolaryngologists). There was significant individual variation in their interest and knowledge of clinical research. However, approximately half of the respondents indicated that they were not interested in and/or had never engaged in clinical research.<br> 　Conclusion : The data collected by this survey contribute to our understanding of the current state of clinical research engagement among junior and mid-career otolaryngologists, and they can serve as a basis for exploring future strategies to increase this engagement. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 79 2 2025 Lower Work Engagement Is Associated with Insomnia, Psychological Distress, and Neck Pain among Junior and Senior High School Teachers in Japan 93 100 EN Rina Tsuchie Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mari Fukuda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideki Tsumura Department of Psychology, Graduate School of Technology, Industrial and Social Sciences, Tokushima University Minako Kinuta Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideyuki Kanda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/68647 School teachers are subject to both physical and mental health problems. We examined cross-sectional relationships between work engagement and major health outcomes among junior and senior high school teachers in Japan via a nationwide survey in 2019-2020. A total of 3,160 respondents were included in the analyses (19.9% response rate). Work engagement was assessed with the Utrecht Work Engagement Scale-9 (UWES-9), and we thus divided the teachers into quartiles according to their UWES-9 scores. Based on validated questionnaires, we assessed insomnia, psychological distress, and neck pain as health outcomes. A binomial logistic regression adjusted for age, gender, school type, teacher’s roles, involvement in club activities, division of duties, employment status, and whether they lived with family demonstrated that the teachers with lower UWES-9 scores had higher burdens of insomnia, psychological distress, and neck pain (odds ratios [95% confidence intervals] in 4th vs. 1st quartile, 2.92 (2.34-3.65), 3.70 (2.81-4.88), and 2.12 (1.68-2.68), respectively; all trend p<0.001). There were no significant differences in these associations between full-time and part-time teachers. Our findings indicate that low work engagement may contribute to physical and mental health issues among junior and senior high school teachers, thus providing insights for preventing health problems in this profession. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 15 1 2025 Association of emergency intensive care unit occupancy due to brain-dead organ donors with ambulance diversion 12633 EN Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Masaki Hisamura Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Our study aims to explore how intensive care unit (ICU) occupancy by brain-dead organ donors affects emergency ambulance diversions. In this retrospective, single-center study at an emergency ICU (EICU), brain-dead organ donors were managed until organ procurement. We classified each day between August 1, 2021, and July 31, 2023, as either an exposure day (any day with a brain-dead organ donor in the EICU from admission to organ procurement) or a control day (all other days). The study compared these days and used multiple logistic regression analysis to assess the impact of EICU occupancy by brain-dead organ donors on ambulance diversions. Over two years, 6,058 emergency patients were transported by ambulance, with 1327 admitted to the EICU, including 13 brain-dead organ donors. Brain-dead donors had longer EICU stays (17 vs. 2 days, P < 0.001). With 168 exposure and 562 control days, EICU occupancy was higher on exposure days (75% vs. 67%, P = 0.003), leading to more ambulance diversions. Logistic regression showed exposure days significantly increased ambulance diversions, with an odds ratio of 1.79 (95% CIs 1.10-2.88). This study shows that managing brain-dead organ donors in the EICU leads to longer stays and higher occupancy, resulting in more frequent ambulance diversions. These findings highlight the critical need for policies that optimize ICU resource allocation while maintaining the infrastructure necessary to support organ donation programs and ensuring continued care for brain-dead donors, who play an essential role in addressing the organ shortage crisis. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1476-5527 2025 The association between objectively measured physical activity and home blood pressure: a population-based real-world data analysis EN Minako Kinuta Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaori Taniguchi Department of Environmental Medicine and Public Health, Izumo, Shimane University Faculty of Medicine Mari Fukuda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriko Nakahata Department of Health and Nutrition, The University of Shimane Faculty of Nursing and Nutrition Hideyuki Kanda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Few studies have examined the association of objectively measured habitual physical activity (PA) and sedentary behavior with out-of-office blood pressure (BP). We investigated the associations of objectively measured PA intensity time, sedentary time, and step count with at-home BP. Using accelerometer-recorded PA indices and self-measured BP in 368 participants (mean age, 53.8 years; 58.7% women), we analyzed 115,575 records of each parameter between May 2019 and April 2024. PA intensities were categorized as light (2.0–2.9 metabolic equivalents [METs]); moderate (3.0–5.9 METs); vigorous (≥6.0 METs), or sedentary (<2.0 METs): the median [interquartile ranges] for these variables was 188 [146–232], 83 [59–114], 1 [0–2], 501 [428–579] minutes, respectively, and for step count, was 6040 [4164–8457]. Means [standard deviations] for systolic and diastolic BP were 116.4 [14.2] and 75.2 [9.3] mmHg, respectively. A mixed-effect model adjusted for possible confounders showed that 1-h longer in vigorous PA was associated with lower systolic and diastolic BP (−1.69 and −1.09 mmHg, respectively). A 1000-step increase in step count was associated with lower systolic and diastolic BP (−0.05 and −0.02 mmHg, respectively). Associations were more pronounced among men and participants aged <60 years. Sedentary time was positively associated with BP in men and participants aged <60 years, but inversely associated with BP in women and participants aged ≥60 years. Our findings suggest that more PA and less sedentary behavior were associated with BP reduction, particularly among men and participants aged <60 years. However, the clinical relevance of this effect remains uncertain because of its modest magnitude. No potential conflict of interest relevant to this article was reported.

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

岡山大学法学会 Acta Medica Okayama 0386-3050 74 3-4 2025 2024年イギリス総選挙：BES 2014-2024 Internet Panel Data の分析 362 314 EN T. Narihiro No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 15 1 2025 Age-specific assessment of initial hemoglobin levels and shock index for predicting life-saving interventions in pediatric blunt liver and spleen injuries 8502 EN Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsuyoshi Iida Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Morihiro Katsura Department of Surgery, Okinawa Chubu Hospital Yutaka Kondo Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital Hideto Yasuda Department of Emergency and Critical Care Medicine, Jichi Medical University Saitama Medical Center Shigeki Kushimoto Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University SHIPPs Study Group This study aimed to evaluate the effectiveness of combining initial hemoglobin levels with the shock index for predicting the need for life-saving interventions (LSI) in pediatric patients with blunt liver and spleen injuries (BLSI), specifically tailored to different age groups. This was a multicenter retrospective cohort study of pediatric patients with BLSI in Japan. The area under the receiver operating characteristic curve (AUROC) were used to assess predictive accuracy. The study included 1,370 patients. LSI was required in 59 of 247 (23.9%) aged 1 to 6 years, 100 of 402 (24.9%) aged 7 to 12 years, and 125 of 297 (42.1%) patients aged 13 to 16 years. Within each specific age group, the predictability was categorized as fair and appeared higher than that of the entire cohort or when using either parameter alone. Notably, in the 1 to 6-year age group, the combined values showed the highest predictability, which was statistically superior to the shock index alone (AUROC of 0.770 vs. 0.671, P = 0.025). Tailoring initial hemoglobin levels and shock index to specific age groups enhances predictability of LSI in pediatric BLSI, showing a fair level of predictive accuracy. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0026-265X 210 2025 A microfluidic paper-based analytical device that uses gelatin film to assay protease activity via time readout 112952 EN Jianchao Ren Department of Chemistry, Okayama University Kaewta Danchana Department of Chemistry, Okayama University Takashi Kaneta Department of Chemistry, Okayama University Food processing, detergents, and pharmaceuticals frequently employ proteases, which are enzymes that break the chemical bonds of both proteins and peptides. In this work, we developed a microfluidic paper-based analytical device (µPAD) for protease activity assays via time readout. To accomplish this, we folded the µPAD to form layers, then inserted a water-insoluble gelatin film between the layers of paper to form the device. Lamination helps to maintain the gelatin film between the introduction zone, which is the upper layer, and the detection channel, which is the lower layer. Proteases decompose the gelatin film when it enters the introduction zone, which then allows it to flow into the detection channel. The protease activity in the sample solution determines the time required to dissolve the gelatin film, which leads to a linear relationship between the logarithm of the protease concentration and the time required to flow the solution a specific distance on the detection channel. The µPAD was used to measure proteases in concentrations that ranged from 0.25 to 1 mg L−1 for bromelain, 2.5 to 10 mg L−1 for papain, and 1 to 8 mg L−1 for trypsin. The limits of quantification for bromelain, papain, and trypsin were 0.41, 2.7, and 9.2 mg mL−1, respectively. The relative standard deviations for bromelain were smaller than 2 % for concentrations ranging from 0.5 to 1.0 mg L−1. We compared the µPAD to a commercially available protease activity assay kit, which relies on quenching fluorescein isothiocyanate-labeled casein. Both methods demonstrated the same order of activity: bromelain > papain > trypsin. The proposed device allowed the assay of bromelain in both pineapple pulp and juice, which were stored at room temperature. When first using the proposed device, the bromelain in the pulp gradually lost its activity, while the activity of the bromelain in the juice showed no significant change for five days. The µPAD requires no analytical instruments for quality control and monitoring of the protease activity in food. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 2377-9608 11 2025 Examining the Long-Term Impact of COVID-19-Induced Clinical Practice Changes on Problem-Solving Behaviors Among Newly Graduated Nurses: A Longitudinal Study EN Takashi Ohue Graduate School of Health Sciences and Faculty of Health Sciences, Okayama University Yuka Ohue Faculty of Nursing, Department of Nursing, Hyogo University Hiroe Harada Faculty of Nursing, Department of Nursing, Hyogo University Objective: This study aimed to longitudinally examine how the cancellation or modification of the clinical practicum due to COVID-19 affected the nursing practice competence of newly graduated nurses in Japan.<br> Methods: A survey was conducted across three periods-June, September, and December 2022-to seek responses from participants. A total of 73 participants (two men and 71 women) who responded in all periods were included in the analysis. The survey included questions on the impact of the integrated and specific clinical practicums, including a self-assessment scale for nursing problem-solving behaviors.<br> Results: During all response periods, those whose practicums were entirely clinical scored significantly higher in nursing problem-solving behaviors. Furthermore, by December, "psychological support to patients for overcoming challenges" improved alongside the clinical experience of newly graduated nurses. However, their practical skills related to aggregating information, identifying improvements in nursing problems, facilitating smooth patient interactions, and individualizing assistance were challenging to improve along with clinical experience.<br> Conclusion: This study revealed that canceling or modifying the clinical practicum owing to COVID-19 impacted the problem-solving behaviors of newly graduated nurses. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1341-321X 31 3 2025 Intention and potential determinants of COVID-19 vaccination among healthcare workers at a single university hospital in Japan, 2024–2025 pre-season 102660 EN Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Yasushi Fujita Division of Infection Prevention and Control, Okayama University Hospital Takashi Kiguchi Division of Infection Prevention and Control, Okayama University Hospital Yohei Manabe Division of Infection Prevention and Control, Okayama University Hospital Background: Financial accessibility has emerged as a significant barrier to vaccine uptake following the cessation of universal public funding for coronavirus disease 2019 (COVID-19) vaccination programs. This investigation assessed the intention and determinant factors of COVID-19 vaccination among healthcare workers in Japan in the 2024–2025 pre-season.<br> Methods: A retrospective survey was conducted utilizing data collected from hospital staff at Okayama University Hospital, Japan, to inform the COVID-19 vaccination strategy in October 2024. The analysis evaluated demographic characteristics, vaccine intention, perceived barriers to vaccination, and maximum acceptable out-of-pocket expenditure.<br> Results: The study population of 3417 respondents comprised 843 medical doctors (24.7 %), 1131 nurses (33.1 %), 320 other medical staff (9.4 %), 286 dental doctors (8.4 %), and 627 administrative officers (18.3 %). At full cost, 2109 (61.7 %) indicated no intention to receive vaccination, while only 4.4 % expressed willingness to be vaccinated and 33.9 % remained undecided. With total self-payment, the vaccination acceptance rates were the highest and lowest among medical doctors (11.4 %) and nurses (1.0 %), respectively. Cost (38.1 %), followed by safety issues (29.5 %) and concerns regarding efficacy or medical necessity (20.3 %), emerged as the primary barrier. The projected vaccination intention increased to 43.9 % and 54.9 % at reduced self-pay costs of 3000 JPY and 5000 JPY, respectively.<br> Conclusions: Addressing financial constraints through policy interventions could be effective strategies in increasing overall vaccination coverage among healthcare workers. In addition, providing tailored education on vaccine safety, efficacy, and necessity may further facilitate increased vaccine uptake within this critical population. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-445X 14 2 2025 Interchangeability of Cross-Platform Orthophotographic and LiDAR Data in DeepLabV3+-Based Land Cover Classification Method 217 EN Shijun Pan Graduate School of Environmental and Life Science, Okayama University Keisuke Yoshida Graduate School of Environmental and Life Science, Okayama University Satoshi Nishiyama Graduate School of Environmental and Life Science, Okayama University Takashi Kojima TOKEN C. E. E. Consultants Co., Ltd. Yutaro Hashimoto Graduate School of Environmental and Life Science, Okayama University Riverine environmental information includes important data to collect, and the data collection still requires personnel's field surveys. These on-site tasks still face significant limitations (i.e., hard or danger to entry). In recent years, as one of the efficient approaches for data collection, air-vehicle-based Light Detection and Ranging technologies have already been applied in global environmental research, i.e., land cover classification (LCC) or environmental monitoring. For this study, the authors specifically focused on seven types of LCC (i.e., bamboo, tree, grass, bare ground, water, road, and clutter) that can be parameterized for flood simulation. A validated airborne LiDAR bathymetry system (ALB) and a UAV-borne green LiDAR System (GLS) were applied in this study for cross-platform analysis of LCC. Furthermore, LiDAR data were visualized using high-contrast color scales to improve the accuracy of land cover classification methods through image fusion techniques. If high-resolution aerial imagery is available, then it must be downscaled to match the resolution of low-resolution point clouds. Cross-platform data interchangeability was assessed by comparing the interchangeability, which measures the absolute difference in overall accuracy (OA) or macro-F1 by comparing the cross-platform interchangeability. It is noteworthy that relying solely on aerial photographs is inadequate for achieving precise labeling, particularly under limited sunlight conditions that can lead to misclassification. In such cases, LiDAR plays a crucial role in facilitating target recognition. All the approaches (i.e., low-resolution digital imagery, LiDAR-derived imagery and image fusion) present results of over 0.65 OA and of around 0.6 macro-F1. The authors found that the vegetation (bamboo, tree, grass) and road species have comparatively better performance compared with clutter and bare ground species. Given the stated conditions, differences in the species derived from different years (ALB from year 2017 and GLS from year 2020) are the main reason. Because the identification of clutter species includes all the items except for the relative species in this research, RGB-based features of the clutter species cannot be substituted easily because of the 3-year gap compared with other species. Derived from on-site reconstruction, the bare ground species also has a further color change between ALB and GLS that leads to decreased interchangeability. In the case of individual species, without considering seasons and platforms, image fusion can classify bamboo and trees with higher F1 scores compared to low-resolution digital imagery and LiDAR-derived imagery, which has especially proved the cross-platform interchangeability in the high vegetation types. In recent years, high-resolution photography (UAV), high-precision LiDAR measurement (ALB, GLS), and satellite imagery have been used. LiDAR measurement equipment is expensive, and measurement opportunities are limited. Based on this, it would be desirable if ALB and GLS could be continuously classified by Artificial Intelligence, and in this study, the authors investigated such data interchangeability. A unique and crucial aspect of this study is exploring the interchangeability of land cover classification models across different LiDAR platforms. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 26 3 2025 LRP4 and Agrin Are Modulated by Cartilage Degeneration and Involved in β-Catenin Signaling in Human Articular Chondrocytes 1007 EN Shuichi Naniwa Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Keiichiro Nishida Locomotive Pain Center, Okayama University Hospital Aki Yoshida Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Yoshihisa Nasu Locomotive Pain Center, Okayama University Hospital Ryuichi Nakahara Locomotive Pain Center, Okayama University Hospital Takashi Ohtsuki Department of Medical Technology, Graduate School of Health Sciences, Okayama University Yoshifumi Hotta Department of Orthopaedic Surgery, Sayo Central Hospital Noriyuki Shimizu Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Chinatsu Ichikawa Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Deting Lin Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Noriaki Otsuka Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University We investigated the roles of low-density lipoprotein receptor-related protein (LRP) 4 and its ligand Agrin in the pathophysiology of cartilage degeneration. Immunohistochemical analysis of human normal articular cartilage and cartilage tissues from patients with osteoarthritis (OA) obtained during surgery of the knee joint showed marked LRP4 expression in the early stages of OA, which then decreased with cartilage degeneration, whereas Agrin was consistently increased with cartilage degeneration. In normal human articular chondrocytes (NHACs), mild cyclic tensile strain (CTS) (0.5 Hz, 5% elongation, 2 h) increased the expression of LRP4 and aggrecan (ACAN), while intense CTS (0.5 Hz, 10% elongation, 6 h) increased the expression of Agrin without affecting LRP4 expression. Treatment with recombinant human (rh) Agrin downregulated the mRNA expression of LRP4 and ACAN, but upregulated the expression of LRP5/6, SRY-box transcription factor 9 (SOX9), Runt-related transcription factor 2 (RUNX2), and a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4). Immunocytochemistry and Western blot analysis showed that rhAgrin treatment upregulated the expression of β-catenin and SOX9. Agrin knockdown by siAGRN transfection partially reduced the nuclear protein expression of β-catenin, which was increased with intense CTS. LRP4 knockdown by siLRP4 transfection increased the expression of LRP5/6, SOX9, RUNX2, ADAMTS-4, and Agrin. These results suggested that intense CTS increases the expression of Agrin, which might interfere with the role of LRP4 in the inhibition of LRP5/6 and their downstream β-catenin signaling, leading to cartilage degeneration. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 1 2025 A Rare Case of Compression Neuritis due to Intraorbital Arteriovenous Fistula (IOAVF) Mimicking Retrobulbar Optic Neuritis 59 64 EN Shun Minakawa Department of Ophthalmology, Japanese Red Cross Society Himeji Hospital Masayuki Hirano Department of Ophthalmology, Japanese Red Cross Society Himeji Hospital Kazuya Takahashi Department of Neurosurgery, Japanese Red Cross Society Himeji Hospital Yuta Imamura Department of Ophthalmology, Japanese Red Cross Society Himeji Hospital Takashi Watanabe Department of Ophthalmology, Japanese Red Cross Society Himeji Hospital Case Report 10.18926/AMO/68363 Intraorbital arteriovenous fistulas (IOAVFs) are rare vascular abnormalities. We describe a case of an IOAVF featuring a direct shunt between the accessory meningeal artery and the superior ophthalmic artery. A 55-year-old woman presented with a 1-month history of visual impairment in her right eye, and magnetic resonance imaging (MRI) revealed optic neuritis-like findings. Steroid pulse therapy temporarily resolved visual impairment. However, 1 month later, she experienced decreased visual acuity, ocular conjunctival hyperemia, edema, and a pulsatile murmur. Contrast-enhanced MRI and digital subtraction angiography revealed compression optic neuropathy due to an IOAVF. Following successful treatment with transarterial embolization, her symptoms disappeared. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1472-6831 25 1 2025 Establishment of a rapid and quantitative method for detecting the range of infection exposure in preclinical dental education 199 EN Ayaka Ueda Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Shinoda-Ito Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazu Takeuchi-Hatanaka Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Takashi Ito Center for Innovative Clinical Medicine, Okayama University Hospital Shintaro Ono Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kimito Hirai Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Omori Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yamamoto The Center for Graduate Medical Education (Dental Division), Okayama University Hospital Shogo Takashiba Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Backgrounds Safe dental treatments that prevent nosocomial and cross-infections are essential for patients and dental workers. However, dental students sometimes pay inadequate attention to infection control, especially in preclinical practice, because of too much focus on technical training, such as the use of equipment, etc. The spread of infections such as SARS-CoV-2, antibiotic-resistant bacteria, and oral bacteria are sometimes lethal for medically compromised patients. Thus, the rapid and inexpensive detection system to detect and measure dental practice-related infection spread during preclinical treatment is highly desired for dental education. This study aimed to establish a method to quantify and visualize infected areas using dental phantoms for safe and effective preclinical dental practices. <br> Methods At first, we developed artificial saliva as an in vitro study, including food-derived bacteria and fluorescence dye, which is safe for application to preclinical practice education. In vitro study, the correlation between adenosine triphosphate (ATP) levels and Lactobacillus colony numbers in yogurt was examined using the ATP fluorescent method, with colony counting on yogurt only and a mixture of yogurt and ultraviolet (UV)-sensitive hand lotion. The mixed liquid of yogurt and hand lotion was used as artificial saliva. Second, we used this artificial saliva in preclinical education. The degree of contamination of personal protective equipment and dental chairs in preclinical practice using this artificial saliva was determined using the ATP fluorescent method and measuring the luminescence areas among 10 dentists, 10 dental residents, and 10 fifth-grade dental students. <br> Results ATP levels and Lactobacillus colony numbers in yogurt were positively correlated with yogurt alone and a mixture of yogurt and UV-sensitive hand lotions (correlation coefficient & efDot; 1). Preclinical education using a mixture of artificial saliva successfully quantified and visualized infectious areas and droplets, which revealed significant differences in ATP amounts in personal protective equipment among groups according to years of experience as dental practitioners (p < 0.05). <br> Conclusions An education system for infection control constructed using artificial saliva containing Lactobacillus and a UV-sensitive fluorescent hand lotion quantified the infectious areas and degrees. Thus, this method is effective in preclinical practice using dental phantoms. No potential conflict of interest relevant to this article was reported.

Proceedings of the National Academy of Sciences Acta Medica Okayama 0027-8424 121 35 2024 Somatic mutations in tumor-infiltrating lymphocytes impact on antitumor immunity e2320189121 EN Fumiaki Mukohara Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuma Iwata Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takamasa Ishino Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Inozume Department of Dermatology, Chiba University Graduate School of Medicine Joji Nagasaki Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Youki Ueda Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University Toshihide Ueno Division of Cellular Signaling, National Cancer Center Research Institute Hideki Ikeda Division of Cell Therapy, Chiba Cancer Research Institute Katsushige Kawase Division of Cell Therapy, Chiba Cancer Research Institute Yuka Saeki Department of Dermatology, Chiba University Graduate School of Medicine Shusuke Kawashima Department of Dermatology, Chiba University Graduate School of Medicine Kazuo Yamashita KOTAI Biotechnologies, Inc. Yu Kawahara Department of Dermatology, Chiba University Graduate School of Medicine Yasuhiro Nakamura Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center Akiko Honobe-Tabuchi Department of Dermatology, University of Yamanashi Hiroko Watanabe Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiromichi Dansako Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsuyoshi Kawamura Department of Dermatology, University of Yamanashi Yutaka Suzuki Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa Hiroaki Honda Department of Pathology, Tokyo Women's Medical University Hiroyuki Mano Division of Cellular Signaling, National Cancer Center Research Institute Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University Masahito Kawazu Division of Cell Therapy, Chiba Cancer Research Institute Yosuke Togashi Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Immune checkpoint inhibitors (ICIs) exert clinical efficacy against various types of cancers by reinvigorating exhausted CD8+ T cells that can expand and directly attack cancer cells (cancer-specific T cells) among tumor-infiltrating lymphocytes (TILs). Although some reports have identified somatic mutations in TILs, their effect on antitumor immunity remains unclear. In this study, we successfully established 18 cancer-specific T cell clones, which have an exhaustion phenotype, from the TILs of four patients with melanoma. We conducted whole-genome sequencing for these T cell clones and identified various somatic mutations in them with high clonality. Among the somatic mutations, an SH2D2A loss-of-function frameshift mutation and TNFAIP3 deletion could activate T cell effector functions in vitro. Furthermore, we generated CD8+ T cell–specific Tnfaip3 knockout mice and showed that Tnfaip3 function loss in CD8+ T cell increased antitumor immunity, leading to remarkable response to PD-1 blockade in vivo. In addition, we analyzed bulk CD3+ T cells from TILs in additional 12 patients and identified an SH2D2A mutation in one patient through amplicon sequencing. These findings suggest that somatic mutations in TILs can affect antitumor immunity and suggest unique biomarkers and therapeutic targets. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 15 1 2025 Cesarean delivery on child health and development in Japanese nationwide birth cohort 2485 EN Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Mitsui Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine Kei Tamai Division of Neonatology, NHO Okayama Medical Center Tomoya Hirota Department of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California San Francisco Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The long-term effects of cesarean delivery (CD) on child health and development remain controversial. This study aimed to investigate these effects using an outcome-wide approach in a Japanese context, where perinatal mortality rates are among the world's lowest. We analyzed data from 2,114 children in a nationwide Japanese birth cohort, linking the 21st Century Longitudinal Survey of Newborns with the Perinatal Research Network database. We examined associations between CD and various health and developmental outcomes up to 9 years of age, including hospitalizations, obesity, and developmental milestones. After adjusting for potential confounders, CD was not significantly associated with most outcomes, including all-cause hospitalization (adjusted risk ratio 1.25, 95% CI 0.997-1.56), obesity at 5.5 and 9 years, and various developmental milestones. Subgroup analyses for multiple births and preterm infants showed some differences in point estimates, but were limited by small sample sizes. CD was not significantly associated with adverse long-term child health or developmental outcomes in this Japanese cohort. These findings provide reassurance regarding CD safety when medically indicated in advanced perinatal care settings. Further research with larger samples and longer follow-up is needed, especially for specific subgroups. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0008-6223 234 2025 Reversible chemical modifications of graphene oxide for enhanced viral capture and release in water 120015 EN Pilar Ferré-Pujol Research Institute for Interdisciplinary Science, Okayama University Seiji Obata Research Institute for Interdisciplinary Science, Okayama University Jésus Raya Institut de Chimie, UMR 7177 CNRS, Université de Strasbourg Alberto Bianco Research Institute for Interdisciplinary Science, Okayama University Hiroyuki Katayama Department of Urban Engineering, School of Engineering, The University of Tokyo Takashi Kato Research Center for Water Environment Technology, School of Engineering, The University of Tokyo Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Detecting low concentrations of viruses in sewage water is crucial for monitoring the spread of emerging viral diseases. However, current detection methods, which involve concentrating viruses using traditional materials such as gauze or cotton, have limitations in effectively accomplishing this task. This study demonstrates that graphene oxide (GO), a two-dimensional carbon material, possesses strong viral adsorption capabilities. However, it lacks efficiency for effective viral release. Therefore, we designed a series of new GO-based materials, which exhibited a viral adsorption similar to pristine GO, while significantly enhancing their release performance by attaching alkyl chains and hydrophilic functional groups. Among the synthesized materials, 1,8-aminooctanol grafted to GO (GO-NH2C8OH) has emerged as the most promising candidate, achieving a viral release rate higher than 50 %. This superior performance can be attributed to the synergistic effect of the alkyl chain and the terminal OH group, which enhances both its affinity for viruses and water dispersibility. Furthermore, we have successfully applied GO-NH2C8OH in a new protocol for concentrating viruses from sewage wastewater. This approach has demonstrated a 200-fold increase in virus concentration, allowing PCR detection of this type of pathogens present in wastewater below the detection limit by direct analysis, underscoring its significant potential for virus surveillance. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1710-1492 21 1 2025 Maternal smoking during infancy increases the risk of allergic diseases in children: a nationwide longitudinal survey in Japan 4 EN Kenji Shigehara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naomi Matsumoto Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mitsuru Tsuge Department of Pediatric Acute Diseases, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Uda Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yukie Saito Department of Pediatrics, Okayama University Hospital Masato Yashiro Department of Pediatrics, Okayama University Hospital Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masanori Ikeda Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background The incidence of allergic diseases has been increasing in Japan. In particular, a serious decline in the age of onset of allergic rhinitis has been observed. Passive smoking from parental smoking has a significant impact on children’s health; however, it is difficult to restrict smoking in the home. While various studies have previously reported on the relationship between passive smoking and the development of allergic diseases in children. However, there have been no reports on passive smoking and allergic diseases on a national scale.<br> Methods Using Japanese national longitudinal survey data (n = 38,444) for newborns born between May 10 and 24, 2010, we assessed parental smoking habits when their children were 6 months old and investigated the association with the development of allergic diseases until the age of 5.5 years. The risk ratios and 95% confidence intervals for the development of different allergic diseases were analyzed after adjusting for potential confounders using Poisson regression with a robust error variance.<br> Results The risk ratio for developing allergic rhinitis/allergic conjunctivitis (AR/AC) in children was significantly higher in the maternal smoking groups ( ≦ 10 cigarettes/day; RR 1.15, 95% CI 1.02–1.30; ≧11 cigarettes/day; RR 1.16, 95% CI 0.93–1.44). Furthermore, associations were found between the maternal smoking group in the presence of paternal smoking and the risk of developing bronchial asthma ( ≦ 10, RR 1.33 95% CI 1.17–1.52; ≧11, RR 1.71 95% CI 1.38–2.1), food allergy ( ≦ 10, RR 1.36 95% CI 1.12–1.63; ≧11, RR 1.25 95% CI 0.84–1.86), atopic dermatitis ( ≦ 10, RR 1.42 95% CI 1.22–1.66; ≧11, RR 1.6 95% CI 1.2–2.13), and AR/AC ( ≦ 10, RR 1.21 95% CI 1.07–1.36; ≧11, RR 1.35 95% CI 1.09–1.67).<br> Conclusions Maternal smoking during infancy increases the risk of developing AR/AC in children. Considering paternal smoking, maternal smoking further increased the risk of developing allergic diseases in children, suggesting that reducing parental smoking at home may reduce the risk of developing allergic diseases in children. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-4409 14 1 2025 Novel Drug Delivery Particles Can Provide Dual Effects on Cancer "Theranostics" in Boron Neutron Capture Therapy 60 EN Abdul Basith Fithroni Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Haruki Inoue Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Shengli Zhou Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Taufik Fatwa Nur Hakim Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takashi Tada Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Minoru Suzuki Institute for Integrated Radiation and Nuclear Science, Kyoto University Yoshinori Sakurai Institute for Integrated Radiation and Nuclear Science, Kyoto University Manabu Ishimoto J-BEAM, Inc. Naoyuki Yamada Nihon Fukushi Fuiin Holding, Co., Ltd. Rani Sauriasari Faculty of Pharmacy, Universitas Indonesia Wolfgang A. G. Sauerwein Deutsche Gesellschaft für Bor-Neutroneneinfangtherapie DGBNCT e.V., University Hospital Essen, Klinik für Strahlentherapie Kazunori Watanabe Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takashi Ohtsuki Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Eiji Matsuura Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Boron (B) neutron capture therapy (BNCT) is a novel non-invasive targeted cancer therapy based on the nuclear capture reaction 10B (n, alpha) 7Li that enables the death of cancer cells without damaging neighboring normal cells. However, the development of clinically approved boron drugs remains challenging. We have previously reported on self-forming nanoparticles for drug delivery consisting of a biodegradable polymer, namely, “AB-type” Lactosome® nanoparticles (AB-Lac particles)- highly loaded with hydrophobic B compounds, namely o-Carborane (Carb) or 1,2-dihexyl-o-Carborane (diC6-Carb), and the latter (diC6-Carb) especially showed the “molecular glue” effect. Here we present in vivo and ex vivo studies with human pancreatic cancer (AsPC-1) cells to find therapeutically optimal formulas and the appropriate treatment conditions for these particles. The biodistribution of the particles was assessed by the tumor/normal tissue ratio (T/N) in terms of tumor/muscle (T/M) and tumor/blood (T/B) ratios using near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG). The in vivo and ex vivo accumulation of B delivered by the injected AB-Lac particles in tumor lesions reached a maximum by 12 h post-injection. Irradiation studies conducted both in vitro and in vivo showed that AB-Lac particles-loaded with either 10B-Carb or 10B-diC6-Carb significantly inhibited the growth of AsPC-1 cancer cells or strongly inhibited their growth, with the latter method being significantly more effective. Surprisingly, a similar in vitro and in vivo irradiation study showed that ICG-labeled AB-Lac particles alone, i.e., without any 10B compounds, also revealed a significant inhibition. Therefore, we expect that our ICG-labeled AB-Lac particles-loaded with 10B compound(s) may be a novel and promising candidate for providing not only NIRF imaging for a practical diagnosis but also the dual therapeutic effects of induced cancer cell death, i.e., “theranostics”. No potential conflict of interest relevant to this article was reported.

AIP Publishing Acta Medica Okayama 0003-6951 126 1 2025 Dynamic domain motion enhancing electro-optic performance in ferroelectric films 012901 EN Shinya Kondo Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuki Okamoto Department of Energy Engineering, Nagoya University Osami Sakata Japan Synchrotron Radiation Research Institute (JASRI) Takashi Teranishi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Akira Kishimoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takanori Nagasaki Department of Energy Engineering, Nagoya University Tomoaki Yamada Department of Energy Engineering, Nagoya University With the rapid advancement of information technology, there is a pressing need to develop ultracompact and energy-efficient thin-film-based electro-optic (EO) devices. A high EO coefficient in ferroelectric materials is crucial. However, substrate clamping can positively or negatively influence various physical properties, including the EO response of these films, thus complicating the development of next-generation thin-film-based devices. This study demonstrates that reversible dynamic domain motion, achieved through substrate clamping, significantly enhances the EO coefficient in epitaxial ferroelectric rhombohedral Pb(Zr, Ti)O3 thin films, where the (111) and (⁠ 111⁠) domains coexist with distinct optical axes. In principle, this approach can be applied to different film-substrate systems, thereby contributing to the advancement of sophisticated EO devices based on ferroelectrics. No potential conflict of interest relevant to this article was reported.

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

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

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 4 2025 古松崇志著『ユーラシア東方の多極共存時代』 287 293 EN Kenya WATANABE 書評 (Book Review) 10.18926/67964 No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1460-2229 2023 Effect of 2-week postpartum check-ups on screening positive for postpartum depression: a population-based cohort study using instrumental variable estimation in Japan cmad074 EN Naoko Nakamura Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Yasuko Nakashima Health Promotion Division, Tsuyama City Department of Children’s Health Naomi Matsumoto Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Postpartum depression is experienced by approximately 10% of women and affects the health and development of their children. Although it is recommended that all mothers have the opportunity for early detection and intervention for postpartum depression, it is unclear whether early postpartum check-ups help to reduce postpartum depression.<br> Objective: The aim of this study was to assess the effect of 2-week postpartum check-ups on screening positive for postpartum depression in Japan.<br> Methods: This was a population-based cohort study that used the administrative database of Tsuyama, Japan. Participants were women who received postpartum home visits from a public health nurse in Tsuyama during the fiscal years 2017–2019. Data were obtained on participant’s attendance at a 2-week postpartum check-up and their responses on the Edinburgh Postpartum Depression Scale. Owing to the initiation of a publicly funded postpartum check-up programme, participants were pseudo-randomly assigned to receive/not receive a 2-week postpartum check-up. We conducted instrumental variable estimation to assess the causal effects of the check-up on screening positive for postpartum depression.<br> Results: The characteristics of the 1,382 participants did not differ by fiscal year of childbirth. We found a 6.7% (95% confidence interval 2.2–11.2) reduction in the prevalence of screening positive for postpartum depression as an effect of 2-week postpartum check-ups among women received 1-month postpartum home visits.<br> Conclusion: The results suggest that 2-week postpartum check-ups are effective in reducing the prevalence of screening positive for postpartum depression among 1-month postpartum women. Despite some limitations, early postpartum care could reduce postpartum depression. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 0934-9723 2024 Trends in the growing impact of group A Streptococcus infection on public health after COVID-19 pandemic: a multicentral observational study in Okayama, Japan EN Shinnosuke Fukushima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Saito Department of General Medicine, NHO Okayama Medical Center Yoshitaka Iwamoto Department of General Medicine, NHO Okayama Medical Center Yuko Takehara Department of Surgery, Okayama Saiseikai General Hospital Haruto Yamada Department of General Medicine, Okayama City Hospital Koji Fujita Department of General Medicine and Infectious Diseases, Tsuyama Chuo Hospital Masayo Yoshida Department of General Medicine, Okayama Kyoritsu Hospital Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Purpose Following the COVID-19 pandemic, group A Streptococcus (GAS) infection has been surging worldwide. We aimed to compare the disease burden between notified cases of streptococcal toxic shock syndrome (STSS) and unreported GAS infections.<br> Methods This is a multicentral observational study, retrospectively performed at seven hospitals in Okayama prefecture in Japan from January 2022, to June 2024. Clinical and microbiological data of patients with positive cultures of GAS were collected from the medical records. Primary outcomes were defined as rates of surgical procedures, intensive care unit (ICU) admission, and in-hospital mortality, which were compared among patients with locally-defined STSS, invasive GAS (iGAS), and non-iGAS infection.<br> Results GAS was detected in 181 patients, with 154 active cases of GAS infection. The number of patients with GAS infection surged in late 2023. The most common source of infection was skin and soft tissue infections, accounting for 83 cases, including 15 cases of necrotizing fasciitis, and 12 cases (7.8%) were notified to public health authorities as STSS. Among the 25 unreported iGAS cases, 9 (36.0%) underwent surgical intervention, and 4 patients (16.0%) required ICU admission. The mortality rates in the unreported iGAS cases were comparable to those observed in the notified STSS.<br> Conclusions We highlighted that the number of iGAS infections was twofold higher than that of notified STSS, with comparable mortality rate between these groups, indicating substantial underestimation of the true burden of iGAS. This epidemiological investigation has significant implications for enhancing infectious disease surveillance frameworks and public health policy development. 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 187 2024 VR 構造力学教材を用いた授業実践から見える中学生のトラス構造理解 111 118 EN Takashi IRIE Faculty of Education, Okayama University 10.18926/bgeou/67898 　中学校技術・家庭科［技術分野］においてプラスチックストロー等の材料で橋を製作させる試みが行われている。橋の強度を確保するための基本はトラス構造であるが，各部材（プラスチックストロー等）に生じる力の大きさとその方向を正確に理解することは生徒にとって難しい。著者はトラス構造を学習するVR構造力学教材を開発し，ストロー橋製作の助けとなる授業実践を行ってきた。この授業実践の中で，生徒がトラス構造の各部材に生じる力を考察するときの誤りのパターンが明らかになった。本研究ではこれまでの授業実践でよく見られた誤り方を生徒に提示し，同じ誤り方をしたかどうか，なぜそのように考えたのかについて調査した上で，求められる指導方法について検討した。 No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-1076 184 1 2024 In vitro fertilization and long-term child health and development: nationwide birth cohort study in Japan 24 EN Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Mitsui Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine Tomoka Kadowaki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Tomoya Hirota Department of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California San Francisco Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The aim of this study is to compare long-term health outcomes between IVF-conceived children and non-IVF-conceived children in Japan, in the context of strong recommendation for single embryo transfer. Using data from a nationwide birth cohort linked with perinatal database, this study analyzed 2140 children born in Japan in May 2010. It compared child health and development outcomes up to 9 years of age between IVF-conceived and non-IVF-conceived children (binary exposure). A Poisson regression with robust variance to estimate the risk ratios for the association between IVF and various long-term child health and developmental outcomes. After adjusting for confounding factors, no significant differences were observed between IVF-conceived and naturally conceived children for most outcomes, including hospitalization, obesity, and developmental milestones. IVF-conceived children showed a slightly lower risk of attention problems at 8 years (adjusted Risk Ratio [aRR]: 0.73, 95% CI: 0.53–1.00). In subgroup analyses, IVF-conceived term children and singletons demonstrated reduced risk of cognitive delays at 5.5 years (aRR: 0.31, 95% CI: 0.10–0.96 and aRR: 0.37, 95% CI: 0.14–0.98, respectively).<br> Conclusion: In this Japanese cohort, IVF conception was not associated with adverse long-term health or developmental outcomes. These findings provide reassurance about the safety of IVF, particularly in the context of single embryo transfer policies. Further research is needed to explore specific IVF protocols and subgroups. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 粗骨材がコンクリート構造物の耐久性に与える影響に関する研究 EN Takashi TANIGUCHI Graduate School of Environmental and Life Science, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 The association between problematic internet use and neck pain among Japanese schoolteachers EN Rina TANABE Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 MicroRNA-34a-5p: A pivotal therapeutic target in gallbladder cancer EN Takashi ODA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 13 22 2024 The Clinical Significance of Interstitial Pneumonia with Autoimmune Features in Cryptogenic Organizing Pneumonia: A Prospective Multicenter Observational Study 6870 EN Hisao Higo Department of Allergy and Respiratory Medicine, Okayama University Hospital Hirohisa Ichikawa Department of Respiratory Medicine, KKR Takamatsu Hospital Yukako Arakawa Department of Respiratory Medicine, KKR Takamatsu Hospital Yoshihiro Mori Department of Respiratory Medicine, KKR Takamatsu Hospital Tomoki Tamura Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center Shoichi Kuyama Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center Chiaki Matsumoto Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital Keisuke Sugimoto Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital Noboru Hamada Department of Respiratory Medicine, Okayama City Hospital Toshimitsu Suwaki Department of Respiratory Medicine, Okayama City Hospital Junko Itano Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Yasushi Tanimoto Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Satoru Senoo Department of Respiratory Medicine, Fukuyama Medical Center Akihiko Taniguchi Department of Respiratory Medicine, Fukuyama Medical Center Yumi Inukai Department of Allergy and Respiratory Medicine, Okayama University Hospital Machiko Arita Department of Respiratory Medicine, Kurashiki Central Hospital Satoko Makimoto Department of Radiology, Okayama University Hospital Katsuhide Kojima Department of Radiology, Okayama University Hospital Takashi Matsushita Department of Dermatology, Kanazawa University Graduate School of Medical Science Yoshinobu Maeda Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nobuaki Miyahara Department of Allergy and Respiratory Medicine, Okayama University Hospital Background: There are cases of idiopathic interstitial pneumonias (IIPs) that do not meet the diagnostic criteria for connective tissue disease but have clinical features suggestive of autoimmune process. Interstitial pneumonia with autoimmune features (IPAF) was recently proposed as a research concept for these patients. Although several prospective studies on IPAF have been conducted, its clinical significance in cryptogenic organizing pneumonia (COP) remains unclear. Methods: Patients aged >= 20 years with suspected COP were prospectively enrolled between June 2018 and December 2022. Among the enrolled patients, those diagnosed with COP based on computed tomography (CT) and bronchoalveolar lavage (BAL) findings were compared between the IPAF and non-IPAF groups. Results: A total of 56 patients were enrolled in this study. Of these, 30 were diagnosed with COP and included in the analysis. Clinical and serological features were positive in two and six patients, respectively. Each feature was exclusive, and eight patients (26.7%) were diagnosed with IPAF. There were no differences between the IPAF and non-IPAF groups in terms of clinical features, including BAL findings, laboratory data, CT findings, and clinical course. During the one-year follow-up period, the frequency of COP exacerbation did not differ between the IPAF and non-IPAF groups, and no cases of systemic autoimmune disease or death occurred in either group. Conclusions: The COP characteristics of the IPAF and non-IPAF groups are similar in all aspects, and distinguishing between the two groups may be of little significance. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 22 2024 Distribution and Incorporation of Extracellular Vesicles into Chondrocytes and Synoviocytes 11942 EN Takashi Ohtsuki Department of Medical Technology, Graduate School of Health Sciences, Okayama University Ikumi Sato Department of Medical Technology, Graduate School of Health Sciences, Okayama University Ren Takashita Department of Medical Technology, Graduate School of Health Sciences, Okayama University Shintaro Kodama Department of Medical Technology, Graduate School of Health Sciences, Okayama University 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 Shogo Watanabe Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takayuki Furumatsu Department of Orthopedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hiroshi Yamada Department of Neuroscience, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Mitsuru Ando Laboratory of Biomaterials, Institute for Life and Medical Sciences, Kyoto University Kazunari Akiyoshi Department of Immunology, Graduate School of Medicine, Kyoto University Keiichiro Nishida Department of Orthopedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Satoshi Hirohata Department of Medical Technology, Graduate School of Health Sciences, Okayama University Osteoarthritis (OA) is a chronic disease affecting over 500 million people worldwide. As the population ages and obesity rates rise, the societal burden of OA is increasing. Pro-inflammatory cytokines, particularly interleukin-1β, are implicated in the pathogenesis of OA. Recent studies suggest that crosstalk between cartilage and synovium contributes to OA development, but the mechanisms remain unclear. Extracellular vesicles (EVs) were purified from cell culture-conditioned medium via ultracentrifugation and confirmed using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. We demonstrated that EVs were taken up by human synoviocytes and chondrocytes in vitro, while in vivo experiments revealed that fluorescent-labelled EVs injected into mouse joints were incorporated into chondrocytes and synoviocytes. EV uptake was significantly inhibited by dynamin-mediated endocytosis inhibitors, indicating that endocytosis plays a major role in this process. Additionally, co-culture experiments with HEK-293 cells expressing red fluorescent protein (RFP)-tagged CD9 and the chondrocytic cell line OUMS-27 confirmed the transfer of RFP-positive EVs across a 600-nm but not a 30-nm filter. These findings suggest that EVs from chondrocytes are released into joint fluid and taken up by cells within the cartilage, potentially facilitating communication between cartilage and synovium. The results underscore the importance of EVs in OA pathophysiology. No potential conflict of interest relevant to this article was reported.

Japan Medical Association Acta Medica Okayama 2433-3298 6 4 2023 Effectiveness of the Original COVID-19 Vaccine against COVID-19 Exacerbations during the Omicron Wave: A Population-based Study in Okayama, Japan 463 469 EN Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Rumi Matsuo Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoka Kadowaki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soshi Takao Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Introduction: In Japan, approximately 97 million individuals have received their primary two doses of coronavirus disease 2019 (COVID-19) vaccine at the end of 2022. In this study, we aim to examine the effectiveness of the primary vaccines and compare its efficacy to booster vaccine shots in terms of preventing COVID-19 exacerbations during the Omicron-predominant period in Japan.<br> Methods: For this analysis, we have collected all the confirmed COVID-19-positive cases from different medical institutions in Okayama City and have also utilized the information from the public Vaccination Record System. Taking the number of vaccinations into consideration, we then conducted a population-based study to assess the effectiveness of the two primary vaccine doses in preventing COVID-19 exacerbations during the Omicron waves. Our primary and secondary outcomes were COVID-19 exacerbations with respiratory failure (i.e., oxygen saturation on room air ≤ 93%, requiring supplemental oxygen), intensive care unit admission and/or mechanical ventilator requirement, or death, in accordance with the Japanese COVID-19 guidelines, and pneumonia during the course of COVID-19 infection, respectively.<br> Results: In total, 95,329 COVID-19-positive individuals, aged 5 years and above, were included in this analysis (study period from January 1 to September 10, 2022). As per our findings, the effectiveness of the primary two doses against COVID-19 exacerbations compared with those who had never been vaccinated was 55.5% (95% confidential interval [CI]: 32.6-71.7), whereas it was higher after the third dose (76.9%; 95% CI: 66.7-84.0) and the fourth dose (75.7%; 95% CI: 58.8-85.7). Effectiveness was sustained for ≥ 5 months after the third vaccination, and preventive effectiveness was observed in individuals aged ≥ 65 years.<br> Conclusions: As per the results of this study, we can conclude that the efficacy of the primary two doses of SARS-CoV-2 vaccine can be further strengthened in terms of preventing COVID-19 exacerbations by administering third and fourth booster vaccine shots. The additional bivalent vaccine is anticipated to further increase its efficacy against the Omicron strain, suggesting that individuals who have not received their booster shots yet should consider getting them to prevent COVID-19 exacerbations. No potential conflict of interest relevant to this article was reported.

Japan Prosthodontic Society Acta Medica Okayama 1883-1958 67 2 2023 Prosthodontic treatment can improve the ingestible food profile in Japanese adult outpatients 189 195 EN Aya Kimura-Ono Center for Innovative Clinical Medicine, Okayama University Hospital Kenji Maekawa Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Takuo Kuboki Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kumiko Nawachi Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Masanori Fujisawa Meikai University School of Dentistry Hironobu Sato Fukuoka Dental College Graduate School of Dental Science Hideki Aita Tohoku University Graduate School of Dentistry Shigeto Koyama Tohoku University Graduate School of Dentistry, Japan Masayuki Hideshima Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences Yuji Sato Showa University School of Dentistry Hiroyuki Wake Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences Kan Nagao Tokushima University Graduate School of Biomedical Sciences Yorika Kodaira-Ueda Tokyo Dental College Katsushi Tamaki Kanagawa Dental University Graduate School Shinsuke Sadamori Ministry of Health, Labour, and Welfare, Chugoku-Shikoku Regional Bureau of Health and Welfare Kazuhiro Tsuga Hiroshima University Graduate School of Biomedical and Health Sciences Yasuhiro Nishi Kagoshima University Graduate School of Medical and Dental Sciences Takashi Sawase Nagasaki University Graduate School of Biomedical Sciences Hisashi Koshino Health Sciences University of Hokkaido School of Dentistry Shin-ichi Masumi Kyushu Dental University Kaoru Sakurai Tokyo Dental College Kanji Ishibashi Iwate Medical University School of Dentistry Takashi Ohyama Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences Yasumasa Akagawa Hiroshima University Graduate School of Biomedical and Health Sciences Toshihiro Hirai Health Sciences University of Hokkaido School of Dentistry Keiichi Sasaki Tohoku University Graduate School of Dentistry Kiyoshi Koyano Kyushu University Faculty of Dental Science Hirofumi Yatani Osaka University Graduate School of Dentistry Hideo Matsumura Nihon University School of Dentistry Tetsuo Ichikawa Tokushima University Graduate School of Biomedical Sciences Shuji Ohkawa Meikai University School of Dentistry Kazuyoshi Baba Showa University School of Dentistry Purpose: To investigate the effect of prosthodontic treatment on the ingestible food profile in adult Japanese outpatients, and to identify the related risk factors that can deteriorate the profile.<br> Methods: The participants were 277 outpatients who visited university-based specialty clinics in Japan for prosthodontic treatment. The demographic data, number of present teeth assessed via intraoral examination, and oral health-related quality of life assessed by the total Oral Health Impact Profile (OHIP-J54) scores of all participants were recorded before treatment. Ingestible food profile score (IFS) was recorded using a validated food intake questionnaire. Eligible participants who answered the questionnaire before and after treatment were categorized into five groups based on the prosthodontic treatments they received (i.e., crowns, bridges, removable partial dentures, removable complete dentures, and removable complete and partial dentures).<br> Results: Multivariate analysis of covariance revealed a statistically significant main effect of prosthodontic intervention (time course: before and after treatment) on mean IFS (P=0.035, F=4.526), even after adjusting for covariates (age, number of present teeth, and treatment modality). Multiple linear regression analysis revealed that the low number of present teeth (r=0.427, P<0.001) and a high OHIP-J54 total score (r=-0.519, P<0.001) of the patients at the baseline were significantly associated with their baseline IFSs, even after adjusting for confounding variables.<br> Conclusions: The findings of this multicenter follow-up study indicate the importance of prosthodontic rehabilitation in improving patients’ ingestible food profiles. No potential conflict of interest relevant to this article was reported.

Japanese Society for Hygiene Acta Medica Okayama 1342-078X 28 2023 Association and dose-response relationship between exposure to alcohol advertising media and current drinking: a nationwide cross-sectional study of Japanese adolescents 58 EN Keita Yoshida Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hideyuki Kanda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuki Kuwabara Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University Aya Kinjo Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University Hisashi Yoshimoto Department of Family Medicine, General Practice and Community Health, Institute of Medicine, University of Tsukuba Teruna Ito Department of Food and Nutrition, Koriyama Women’s University Hideaki Kasuga Department of Hygiene and Preventive Medicine, Fukushima Medical University Ruriko Minobe National Institute of Alcoholism, Kurihama National Hospital Hitoshi Maesato National Institute of Alcoholism, Kurihama National Hospital Maki Jike Department of Food Science and Nutrition, Faculty of Life and Environmental Science, Showa Women’s University Yuuki Matsumoto Division of Public Health, Department of Social Medicine, Nihon University School of Medicine Yuichiro Otsuka Division of Public Health, Department of Social Medicine, Nihon University School of Medicine Osamu Itani Division of Public Health, Department of Social Medicine, Nihon University School of Medicine Yoshitaka Kaneita Division of Public Health, Department of Social Medicine, Nihon University School of Medicine Susumu Higuchi National Institute of Alcoholism, Kurihama National Hospital Yoneatsu Osaki Division of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of Medicine, Tottori University Background: Underage drinking is a public health concern. However, few studies have examined the association between alcoholic beverage advertising and underage drinking, particularly in countries with low underage drinking rates, such as Japan. Therefore, we aimed to investigate the relationship between exposure to advertising in various media and alcohol drinking among Japanese adolescents.<br> Methods: We conducted a cross-sectional study involving 15,683 adolescents (51% girls) using data from a nationwide lifestyle survey in 2021 among junior and senior high schools across Japan. Media types were websites, stores, and public transportation. We defined current drinking as alcohol consumption of ≥1 day in the 30 days preceding the survey. Multivariable logistic regression was used to examine the association between exposure to alcohol advertisements and current drinking, adjusting for sex, grades, school area, lifestyle (bedtime and having fun at school), and addictive behaviors (smoking status and parents’ alcohol consumption).<br> Results: The prevalence of current drinking was 2.2% (2.3% of boys and 2.0% of girls). Students who were exposed to any alcohol advertising media had higher odds of current drinking compared with those who were not (odds ratio, 1.48; 95% confidence interval [CI], 1.18–1.87). Students who were exposed to web, in-store, and public transportation advertisements had odds ratios of 1.44 (95% CI, 1.14–1.81), 1.62 (1.28–2.05), and 1.45 (1.06–1.98) of current drinking, respectively, compared with those who were not. The association of exposure to alcohol advertising media with the prevalence of current drinking was similar among boys and girls (all p for sex interaction >0.1), except for that of exposure to web advertisements; its association with current drinking was more pronounced in girls (p for sex interaction = 0.046). Exposure to a larger cumulative number of different alcohol advertising media was independently associated with a higher prevalence of current drinking among all students, boys, and girls (p-values for trend <0.001, 0.031, and <0.001, respectively; p for sex interaction = 0.085).<br> Conclusions: We found an association with a dose-response relationship between exposure to alcohol advertisements and current drinking among adolescents in junior and senior high schools across Japan. Our findings highlight the need for further advertising regulations to prevent underage drinking. No potential conflict of interest relevant to this article was reported.

Japan Medical Association Acta Medica Okayama 2433-3298 6 2 2023 Disease and Injury Trends following Heavy Rains in Western Japan in 2018 129 137 EN Chiaki Hashimoto Department of Epidemiology, Graduate School of Medicine, Density and Pharmaceutical Sciences Okayama University Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Density and Pharmaceutical Sciences Okayama University Kazuharu Murakami Mabi Memorial Hospital Shigeru Suganami Association of Medical Doctors of Asia Introduction: Torrential rains occurred in Okayama in western Japan in July 2018, forcing local residents to evacuate. Few studies have reported early-phase disease and injury trends among patients following torrential rains. Thus, in this study, we assessed the illness and injury trends among patients who visited temporary medical facilities located in the areas affected by the 2018 torrential rains; these facilities opened 10 d after the disaster.<br> Methods: We evaluated the trends among patients who visited a medical clinic located in the area in western Japan affected by heavy rains in 2018. We reviewed medical charts related to 1,301 outpatient visits and conducted descriptive analyses.<br> Results: More than half of the patients were over 60 years old. The patients experienced mild injuries (7.9% of total visits) as well as common diseases such as hypertensive diseases (30%), diabetes mellitus (7.8%), acute upper respiratory infections (5.4%), skin diseases (5.4%), and eye diseases (4.8%). Hypertensive diseases were the main cause of a visit in any week. Eye problems were the second-highest reason for a visit in the first week, but there was a relative decrease from the first to the third week. Additionally, the proportion of injuries and skin diseases increased from the first to the second week, from 7.9% to 11.1% for injuries, and from 3.9% to 6.7% for skin diseases.<br> Conclusions: The types of diseases changed on a weekly basis. Older adults needed medical support for longer than other age groups. Prior preparedness such as earlier deployment of such temporary clinics can help mitigate the damage to the victims. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 14 1 2024 A nationwide longitudinal survey of infantile injury and its recurrence in Japan 24716 EN Tomohiro Hiraoka Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Masaki Hisamura Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Injury recurrence in young children is a significant public health concern, as it may indicate an unfavorable home environment. This study evaluates whether infantile injuries increase recurrence during preschool years, contributing to more effective prevention strategies for vulnerable families. The study included 20,191 children from "The Longitudinal Survey of Babies in the 21st Century," a representative sample of infants born in Japan between May 10 and 24, 2010. We conducted a logistic regression analysis to compare injury recurrence risk between children aged 18 months to seven years with and without infantile injury histories. The study revealed that infants with a history of injuries had a higher risk of subsequent hospital visits for injuries during preschool years (crude Odds Ratio (cOR) 1.52, 95% CI, 1.41-1.64, adjusted OR (aOR) 1.48, 95% CI 1.37-1.60). Specific injuries, such as falls (aOR 1.34, 95% CI, 1.26-1.43), pinches (aOR 1.22, 95% CI, 1.15-1.29), drowning (aOR 1.29, 95% CI, 1.19-1.40), ingestion (aOR 1.35, 95% CI, 1.17-1.55), and burns (aOR 1.47, 95% CI, 1.31-1.65), independently increased the risk of future injuries. Our findings highlight the necessity of universal safety measures in the home environment and targeted interventions for families with a history of high-risk injuries. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1478-6354 26 1 2024 Clinical practice pattern of Pneumocystis pneumonia prophylaxis in systemic lupus erythematosus: a cross-sectional study from lupus registry of nationwide institutions (LUNA) 198 EN Takahisa Onishi Department of Rheumatology, Kakogawa Central City Hospital Ken-Ei Sada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Keigo Hayashi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yoshia Miyawaki Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ryusuke Yoshimi Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine Yasuhiro Shimojima Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine Shigeru Ohno Center for Rheumatic Diseases, Yokohama City University Medical Center Hiroshi Kajiyama Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University Kunihiro Ichinose Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Shuzo Sato Department of Rheumatology, Fukushima Medical University School of Medicine Michio Fujiwara Department of Rheumatology, Yokohama Rosai Hospital Nobuyuki Yajima Division of Rheumatology, Department of Medicine, Showa University School of Medicine Takashi Kida Infammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Yusuke Matsuo Department of Rheumatology, Tokyo Kyosai Hospital Keisuke Nishimura Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine Takashi Yamane Department of Rheumatology, Kakogawa Central City Hospital Background Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in patients undergoing immunosuppressive therapy, such as glucocorticoid (GC) medication, for systemic autoimmune diseases like systemic lupus erythematosus (SLE). Despite the confirmed effectiveness of PCP prophylaxis, its clinical administration, especially in conjunction with GC dosage, remains unclear. We aimed to describe the clinical practice of PCP prophylaxis in association with SLE in Japan, evaluate the relationship between GC dosage and PCP prophylaxis, and explore the practice patterns associated with PCP prophylaxis. <br> Methods This cross-sectional study used data from the Lupus Registry of Nationwide Institutions in Japan from 2016 to 2021 and included patients diagnosed with SLE. Using descriptive statistics, multivariate analysis, and decision tree analysis, we examined the prevalence of PCP prophylaxis and its association with the GC dosage. <br> Results Out of 1,460 patients, 21% underwent PCP prophylaxis. The frequency of prophylaxis decreased with a decrease in GC dosage. After adjusting for confounders, logistic regression revealed the odds ratio of PCP prophylaxis increased with higher prednisolone (PSL) doses: 3.7 for 5 <= PSL < 7.5 mg, 5.2 for 7.5 <= PSL < 10 mg, 9.0 for 10 <= PSL < 20 mg, and 43.1 for PSL >= 20 mg, using PSL < 5 mg as the reference. Decision tree analysis indicated that a PSL dosage of < 11 mg/day and immunosuppressant use were key determinants of PCP prophylaxis. <br> Conclusion This study provides valuable insights into PCP prophylaxis practices in patients with SLE in Japan, underscoring the importance of GC dosage and concomitant immunosuppressant use. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 21 2024 Epigenetic Regulation of CXC Chemokine Expression by Environmental Electrophiles Through DNA Methyltransferase Inhibition 11592 EN Tomoki Tsuchida Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sho Kubota Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shizuki Kamiuezono Department of Medicinal Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University Nobumasa Takasugi Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Ito School of Life Sciences, Tokyo University of Pharmacy and Life Sciences Yoshito Kumagai Graduate School of Pharmaceutical Sciences, Kyushu University Takashi Uehara Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ubiquitously distributed environmental electrophiles covalently modify DNA and proteins, potentially leading to adverse health effects. However, the impacts of specific electrophiles on target proteins and their physiological roles remain largely unknown. In the present study, we focused on DNA methylation, which regulates gene expression and physiological responses. A total of 45 environmental electrophiles were screened for inhibitory effects on the activity of DNA methyltransferase 3B (DNMT3B), a key enzyme in DNA methylation, and four compounds were identified. We focused on 1,2-naphthoquinone (1,2-NQ), an air pollutant whose toxicity has been reported previously. Interestingly, we found that 1,2-NQ modified multiple lysine and histidine residues in DNMT3B, one of which was near the active site in DNMT3B. It was found that 1,2-NQ altered gene expression and evoked inflammatory responses in lung adenocarcinoma cell lines. Furthermore, we found that 1,2-NQ upregulated CXCL8 expression through DNA demethylation of the distal enhancer and promoted cancer cell growth. Our study reveals novel mechanisms of epigenetic regulation by environmental electrophiles through the inhibition of DNMT3B activity and suggests their physiological impact. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0085-2538 106 5 2024 A randomized, open-label, clinical trial examined the effects of canagliflozin on albuminuria and eGFR decline using an individual pre-intervention eGFR slope 972 984 EN Satoshi Miyamoto Center for Innovative Clinical Medicine, Okayama University Hospital Hiddo J.L. Heerspink Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen Dick de Zeeuw Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen Kota Sakamoto Center for Innovative Clinical Medicine, Okayama University Hospital Michihiro Yoshida Center for Innovative Clinical Medicine, Okayama University Hospital Masao Toyoda Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine Daisuke Suzuki Suzuki Diadetes Clinic Takashi Hatanaka Department of Diabetes and Endocrinology, National Hospital Organization Fukuyama Medical Center Tohru Nakamura Diabetes Internal Medicine, Sumitomo Besshi Hospital Shinji Kamei Department of Diabetic Medicine, Kurashiki Central Hospital Satoshi Murao Department of Diabetes and Endocrinology, Takamatsu Hospital Kazuyuki Hida Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center Shinichiro Ando Department of Internal Medicine Diabetic Center, Okayama City Hospital Hiroaki Akai Division of Diabetes and Metabolism, Faculty of Medicine, Tohoku Medical and Pharmaceutical University Yasushi Takahashi Department of Diabetes, Ochiai General Hospital Munehiro Kitada Department of Diabetology and Endocrinology, Kanazawa Medical University Hisashi Sugano Department of Diabetes and Endocrinology, Kochi Health Sciences Center Tomokazu Nunoue Nunoue Clinic Akihiko Nakamura Internal Medicine, Osafune Clinic Motofumi Sasaki Department of Diabetes and Endocrinology, Matsue City Hospital Tatsuaki Nakatou Diabetes Center, Okayama Saiseikai General Hospital Kei Fujimoto Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, The Jikei University Kashiwa Hospital Daiji Kawanami Department of Endocrinology and Diabetes, Fukuoka University School of Medicine Takashi Wada Department of Nephrology and Laboratory Medicine, Graduate School of Medical Sciences, Kanazawa University Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Hiromi Kuramoto Center for Innovative Clinical Medicine, Okayama University Hospital Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital Demonstrating drug efficacy in slowing kidney disease progression requires large clinical trials when targeting participants with an early stage of chronic kidney disease (CKD). In this randomized, parallel-group, open-labeled trial (CANPIONE study), we assessed the effect of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin using the individual’s change in estimated glomerular filtration rate (eGFR) slope before (pre-intervention slope) and during treatment (chronic slope). We randomly assigned (1:1) participants with type 2 diabetes, urinary albumin-to-creatinine ratio (UACR) of 50 to under 300 mg/g, and an eGFR of at least 45 ml/min/1.73m2 to receive canagliflozin or guideline-recommended treatment except for SGLT2 inhibitors (control). The first and second primary outcomes were the geometric mean percentage change from baseline in UACR and the change in eGFR slope, respectively. Of 98 randomized participants, 96 received at least one study treatment. The least-squares mean change from baseline in log-transformed geometric mean UACR was significantly greater in the canagliflozin group than the control group (between group-difference, −30.8% (95% confidence interval −42.6 to −16.8). The between-group difference (canagliflozin group – control group) of change in eGFR slope (chronic – pre-intervention) was 4.4 (1.6 to 7.3) ml/min/1.73 m2 per year, which was more pronounced in participants with faster eGFR decline. In summary, canagliflozin reduced albuminuria and the participant-specific natural course of eGFR decline in participants with type 2 diabetes and microalbuminuria. Thus, the CANPIONE study suggests that the within-individual change in eGFR slope may be a novel approach to determine the kidney protective potential of new therapies in early stages of CKD. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1083-351X 300 3 2024 Methyl vinyl ketone and its analogs covalently modify PI3K and alter physiological functions by inhibiting PI3K signaling 105679 EN Atsushi Morimoto Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nobumasa Takasugi Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuexuan Pan Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sho Kubota Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoshi Dohmae Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science Yumi Abiko Graduate School of Biomedical Science, Nagasaki University Koji Uchida Laboratory of Food Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo Yoshito Kumagai Graduate School of Pharmaceutical Sciences, Kyushu University Takashi Uehara Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Reactive carbonyl species (RCS), which are abundant in the environment and are produced in vivo under stress, covalently bind to nucleophilic residues such as Cys in proteins. Disruption of protein function by RCS exposure is predicted to play a role in the development of various diseases such as cancer and metabolic disorders, but most studies on RCS have been limited to simple cytotoxicity validation, leaving their target proteins and resulting physiological changes unknown. In this study, we focused on methyl vinyl ketone (MVK), which is one of the main RCS found in cigarette smoke and exhaust gas. We found that MVK suppressed PI3K-Akt signaling, which regulates processes involved in cellular homeostasis, including cell proliferation, autophagy, and glucose metabolism. Interestingly, MVK inhibits the interaction between the epidermal growth factor receptor and PI3K. Cys656 in the SH2 domain of the PI3K p85 subunit, which is the covalently binding site of MVK, is important for this interaction. Suppression of PI3K- Akt signaling by MVK reversed epidermal growth factor- induced negative regulation of autophagy and attenuated glucose uptake. Furthermore, we analyzed the effects of the 23 RCS compounds with structures similar to MVK and showed that their analogs also suppressed PI3K-Akt signaling in a manner that correlated with their similarities to MVK. Our study demonstrates the mechanism of MVK and its analogs in suppressing PI3K-Akt signaling and modulating physiological functions, providing a model for future studies analyzing environmental reactive species. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0340-5761 99 2 2024 Therapeutic potential of 4-phenylbutyric acid against methylmercury-induced neuronal cell death in mice 563 574 EN Ryohei Miki Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryosuke Nomura Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuta Iijima Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sho Kubota Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nobumasa Takasugi Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takao Iwawaki Division of Cell Medicine, Department of Life Science, Medical Research Institute, Kanazawa Medical University Masatake Fujimura Department of International Affairs and Research, National Institute for Minamata Disease Takashi Uehara Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Methylmercury (MeHg) is an environmental neurotoxin that induces damage to the central nervous system and is the causative agent in Minamata disease. The mechanisms underlying MeHg neurotoxicity remain largely unknown, and there is a need for effective therapeutic agents, such as those that target MeHg-induced endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), which is activated as a defense mechanism. We investigated whether intraperitoneal administration of the chemical chaperone, 4-phenylbutyric acid (4-PBA), at 120 mg/kg/day can alleviate neurotoxicity in the brains of mice administered 50 ppm MeHg in drinking water for 5 weeks. 4-PBA significantly reduced MeHg-induced ER stress, neuronal apoptosis, and neurological symptoms. Furthermore, 4-PBA was effective even when administered 2 weeks after the initiation of exposure to 30 ppm MeHg in drinking water. Our results strongly indicate that ER stress and the UPR are key processes involved in MeHg toxicity, and that 4-PBA is a novel therapeutic candidate for MeHg-induced neurotoxicity. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2079-4991 14 20 2024 Colossal Dielectric Constant of Nanocrystalline/Amorphous Homo-Composite BaTiO3 Films Deposited via Pulsed Laser Deposition Technique 1677 EN Shinya Kondo Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Taichi Murakami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Loick Pichon Institut National de la Recherche Scientifique (INRS), Centre Énergie, Matériaux et Télécommunications Joel Leblanc-Lavoie Institut National de la Recherche Scientifique (INRS), Centre Énergie, Matériaux et Télécommunications Takashi Teranishi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Akira Kishimoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Khakani, My Ali El Khakani Institut National de la Recherche Scientifique (INRS), Centre Énergie, Matériaux et Télécommunications We report the pulsed laser deposition (PLD) of nanocrystalline/amorphous homo-composite BaTiO3 (BTO) films exhibiting an unprecedented combination of a colossal dielectric constant (epsilon(r)) and extremely low dielectric loss (tan delta). By varying the substrate deposition temperature (T-d) over a wide range (300-800 degrees C), we identified T-d = 550 degrees C as the optimal temperature for growing BTO films with an epsilon(r) as high as similar to 3060 and a tan delta as low as 0.04 (at 20 kHz). High-resolution transmission electron microscopy revealed that the PLD-BTO films consist of BTO nanocrystals (similar to 20-30 nm size) embedded within an otherwise amorphous BTO matrix. The impressive dielectric behavior is attributed to the combination of highly crystallized small BTO nanograins, which amplify interfacial polarization, and the surrounding amorphous matrix, which effectively isolates the nanograins from charge carrier transport. Our findings could facilitate the development of next-generation integrated dielectric devices. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 Prognostic Efficacy of the Albumin Grade in Patients with Hepatocellular Carcinoma 377 386 EN Yuichi Hirano Department of Gastroenterology, Okayama City Hospital Kazuhiro Nouso Department of Gastroenterology, Okayama City Hospital Kazuya Kariyama Department of Gastroenterology, Okayama City Hospital Atsushi Hiraoka Gastroenterology Center, Ehime Prefectural Central Hospital Shohei Shiota Department of Gastroenterology, Okayama City Hospital Akiko Wakuta Department of Gastroenterology, Okayama City Hospital Satoshi Yasuda Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital Hidenori Toyoda Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital Kunihiko Tsuji Center of Gastroenterology, Teine Keijinkai Hospital Takeshi Hatanaka Department of Gastroenterology, Saiseikai Maebashi Hospital Satoru Kakizaki Department of Clinical Research, NHO Takasaki General Medical Center Atsushi Naganuma Department of Gastroenterology, NHO Takasaki General Medical Center Toshifumi Tada Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital Ei Itobayashi Department of Gastroenterology, Asahi General Hospital Toru Ishikawa Department of Gastroenterology, Saiseikai Niigata Hospital Noritomo Shimada Division of Gastroenterology and Hepatology, Otakanomori Hospital Koichi Takaguchi Department of Hepatology, Kagawa Prefectural Central Hospital Akemi Tsutsui Department of Hepatology, Kagawa Prefectural Central Hospital Takuya Nagano Department of Hepatology, Kagawa Prefectural Central Hospital Michitaka Imai Department of Gastroenterology, Niigata Cancer Center Hospital Shinichiro Nakamura Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital Takashi Kumada Department of Nursing, Gifu Kyoritsu University Real-Life Practice Experts for HCC (RELPEC) Study Group in Japan Original Article 10.18926/AMO/67662 We previously found that “albumin grade”, formerly called the “ALBS grade,” demonstrated significant capability for prognostic stratification in hepatocellular carcinoma (HCC) patients treated with lenvatinib. The purpose of the present study was to compare the performance of the albumin grade with that of the modified albumin-bilirubin (mALBI) grade in predicting overall survival of HCC patients with different BCLC stages and treatment types. We enrolled 7,645 Japanese patients newly diagnosed with HCC using the Akaike information criteria (AIC), likelihood ratio, and C-index in different Barcelona Clinic Liver Cancer (BCLC) stages and treatments. The albumin grade showed similar and slightly better performance than the mALBI grade for BCLC stage 0 and A and especially for patients who underwent curative surgery and ablation. In patients treated with transcatheter arterial chemoembolization, molecular targeted agents, and the best supportive care, the mALBI grade had better performance than the albumin grade. However, the differences of the indices were very small in all scenarios. Overall, the albumin grade was comparable in efficacy to the mALBI grade, showing particular benefit for patients with early-stage HCC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 Small-for-Gestational-Age Status and the Risk of Kawasaki Disease: A Nationwide Birth Cohort in Japan 363 370 EN Satoe Takanaga Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoka Kadowaki Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soshi Takao Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Original Article 10.18926/AMO/67656 Kawasaki disease (KD) is a pediatric disease of unknown etiology that commonly affects infants in East Asia. Infants born small for gestational age (SGA) have weaker immune systems and are more susceptible to infection. Using data from a nationwide Japanese birth cohort study conducted in 2010 (n=34,579), we investigated whether SGA increases the risk of KD. SGA was defined as birth weight below the 10th percentile for gestational age. The outcome was hospitalization for KD between 6 and 30 months of age. The association between SGA and hospitalization for KD, adjusted for child and maternal factors, was examined using logistic regression. Of the 231 children hospitalized for KD, 9.5% were SGA. Further statistical analysis showed that SGA did not increase the odds ratio (OR) of hospitalization for KD (adjusted OR 1.12, 95% confidence interval 0.71-1.75). This result was not changed with stratification by early daycare attendance and preterm status. Reasons for the lack of association may include the multifactorial pathogenesis of KD; in addition, the types of infections to which SGA infants are predisposed may differ from those triggering KD. Overall, our large nationwide study found no association between SGA and KD. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1618-2642 416 28 2024 Comparison of protein immobilization methods with covalent bonding on paper for paper-based enzyme-linked immunosorbent assay 6679 6686 EN Yang Chen Department of Chemistry, Okayama University Kaewta Danchana Department of Chemistry, Okayama University Takashi Kaneta Department of Chemistry, Okayama University In this study, two methods were examined to optimize the immobilization of antibodies on paper when conducting a paper-based enzyme-linked immunosorbent assay (P-ELISA). Human IgG, as a test-capture protein, was immobilized on paper via the formation of Schiff bases. Aldehyde groups were introduced onto the surface of the paper via two methods: NaIO4 and 3-aminopropyltriethoxysilane (APTS) with glutaraldehyde (APTS-glutaraldehyde). In the assay, horseradish peroxidase-conjugated anti-human IgG (HRP-anti-IgG) binds to the immobilized human IgG, and the colorimetric reaction of 3,3′,5,5′-tetramethylbenzyzine (TMB) produces a blue color in the presence of H2O2 and HRP-anti-IgG as a model analyte. The immobilization of human IgG, the enzymatic reaction conditions, and the reduction of the chemical bond between the paper surface and immobilized human IgG all were optimized in order to improve both the analytical performance and the stability. In addition, the thickness of the paper was examined to stabilize the analytical signal. Consequently, the APTS-glutaraldehyde method was superior to the NaIO4 method in terms of sensitivity and reproducibility. Conversely, the reduction of imine to amine with NaBH4 proved to exert only minimal influence on sensitivity and stability, although it tended to degrade reproducibility. We also found that thick paper was preferential when using P-ELISA because a rigid paper substrate prevents distortion of the paper surface that is often caused by repeated washing processes. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2504-446X 8 9 2024 Generating 3D Models for UAV-Based Detection of Riparian PET Plastic Bottle Waste: Integrating Local Social Media and InstantMesh 471 EN Shijun Pan Graduate School of Environmental and Life Science, Okayama University Keisuke Yoshida Graduate School of Environmental and Life Science, Okayama University Daichi Shimoe Graduate School of Environmental and Life Science, Okayama University Takashi Kojima TOKEN C.E.E. Consultants Co., Ltd. Satoshi Nishiyama Graduate School of Environmental and Life Science, Okayama University In recent years, waste pollution has become a severe threat to riparian environments worldwide. Along with the advancement of deep learning (DL) algorithms (i.e., object detection models), related techniques have become useful for practical applications. This work attempts to develop a data generation approach to generate datasets for small target recognition, especially for recognition in remote sensing images. A relevant point is that similarity between data used for model training and data used for testing is crucially important for object detection model performance. Therefore, obtaining training data with high similarity to the monitored objects is a key objective of this study. Currently, Artificial Intelligence Generated Content (AIGC), such as single target objects generated by Luma AI, is a promising data source for DL-based object detection models. However, most of the training data supporting the generated results are not from Japan. Consequently, the generated data are less similar to monitored objects in Japan, having, for example, different label colors, shapes, and designs. For this study, the authors developed a data generation approach by combining social media (Clean-Up Okayama) and single-image-based 3D model generation algorithms (e.g., InstantMesh) to provide a reliable reference for future generations of localized data. The trained YOLOv8 model in this research, obtained from the S2PS (Similar to Practical Situation) AIGC dataset, produced encouraging results (high F1 scores, approximately 0.9) in scenario-controlled UAV-based riparian PET bottle waste identification tasks. The results of this study show the potential of AIGC to supplement or replace real-world data collection and reduce the on-site work load. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 1664-462X 15 2024 Illumina-based transcriptomic analysis of the fast-growing leguminous tree Acacia crassicarpa: functional gene annotation and identification of novel SSR-markers 1339958 EN Shougo Ishio Tsukuba Research Institute, Sumitomo Forestry Co. Ltd. Kazutaka Kusunoki Tsukuba Research Institute, Sumitomo Forestry Co. Ltd. Michiko Nemoto Graduate School of Environment, Life, Natural Science and Technology, Okayama University Tadayoshi Kanao Graduate School of Environment, Life, Natural Science and Technology, Okayama University Takashi Tamura Institute of Global Human Resource Development, Okayama University Acacia crassicarpa is a fast-growing leguminous tree that is widely cultivated in tropical areas such as Indonesia, Malaysia, Australia, and southern China. This tree has versatile utility in timber, furniture, and pulp production. Illumina sequencing of A. crassicarpa was conducted, and the raw data of 124,410,892 reads were filtered and assembled de novo into 93,317 unigenes, with a total of 84,411,793 bases. Blast2GO annotation, Benchmark Universal Single-Copy Ortholog evaluation, and GO-term classification produced a catalogue of unigenes for studying primary metabolism, phytohormone signaling, and transcription factors. Massive transcriptomic analysis has identified microsatellites composed of simple sequence repeat (SSR) loci representing di-, tri-, and tetranucleotide repeat units in the predicted open reading frames. Polymorphism was induced by PCR amplification of microsatellite loci located in several genes encoding auxin response factors and other transcription factors, which successfully distinguished 16 local trees of A. crassicarpa tested, representing potentially exploitable molecular markers for efficient tree breeding for plantation and biomass exploitation. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2666-8319 10 2024 Reduction with zinc - Impact on the determination of nitrite and nitrate ions using microfluidic paper-based analytical devices 100347 EN Mika I. Umeda Okayama University Kaewta Danchana Okayama University Takatoshi Fujii National Institute of Technology, Yonago College Eiichi Hino National Institute of Technology, Yonago College Yusuke Date National Institute of Technology, Yonago College Kaoru Aoki National Institute of Technology, Yonago College Takashi Kaneta Okayama University We used a microfluidic paper-based analytical device (mu PAD) to investigate the influence that zinc reduction exerts on the determination of nitrite and nitrate ions in natural water samples. The mu PAD consists of layered channels for the reduction of nitrate to nitrite with zinc powder and the subsequent detection of nitrite with Griess reagent. The amount of zinc, number of layers, and reaction time for the reduction were optimized to obtain an intense signal for nitrate. Initially, the sensitivity to nitrate corresponded to 55% that of nitrite, which implied an incomplete reduction. We found, however, that zinc decreased the sensitivity to nitrite in both the mu PAD and spectrophotometry. The sensitivity to nitrite was decreased by 48% in spectrophotometry and 68% in the mu PAD following the reaction with zinc. One of the reasons for the decreased sensitivity is attributed to the production of ammonia, as we elucidated that both nitrite and nitrate produced ammonia via the reaction with zinc. The results suggest that the total concentration of nitrite and nitrate must be corrected by constructing a calibration curve for nitrite with zinc, in addition to developing curves for nitrate with zinc and for nitrite without zinc. Using these calibration curves, the absorbance at different concentration ratios of nitrite and nitrate ions could be reproduced via calculation using the calibration curves with zinc for nitrite and nitrate. Eventually, the developed mu PAD was applied to the determination of nitrite and nitrate ions in natural water samples, and the results were compared with those using a conventional spectrophotometric method. The results of the mu PAD are in good agreement with those of conventional spectrophotometry, which suggests that the mu PAD is reliable for the measurement of nitrite and nitrate ions in natural water samples. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 136 2 2024 IoT 技術を用いた家庭血圧管理研究の５年間の成果と時系列ビックデータ・AI を活用した今後の展望：益田研究 57 62 EN Takashi Hisamatsu Department of Public Health, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Minako Kinuta Department of Public Health, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mari Fukuda Department of Public Health, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kaori Taniguchi Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University Noriko Nakahata Department of Health and Nutrition, Faculty of Nursing and Nutrition, The University of Shimane Hideyuki Kanda Department of Public Health, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2769-2558 3 3 2024 Forgetfulness in adult attention-deficit/hyperactivity disorder masks transient epileptic amnesia: a case report e70003 EN Takashi Fukao Department of Neuropsychiatry, OkayamaUniversity Hospital Masaki Fujiwara Department of Neuropsychiatry, OkayamaUniversity Hospital Yuto Yamada Department of Neuropsychiatry, OkayamaUniversity Hospital Shinji Sakamoto Department of Neuropsychiatry, OkayamaUniversity Hospital Yosuke Matsumoto Okayama University Hospital Gender Center Manabu Takaki Department of Neuropsychiatry, OkayamaUniversity Faculty of Medicine, Dentistry andPharmaceutical Sciences Background: Inattention due to attention-deficit/hyperactivity disorder (ADHD) can lead to forgetfulness. Transient epileptic amnesia (TEA) can cause forgetfulness, similar to ADHD. We report a patient with ADHD who developed TEA.<br> Case Presentation: The patient was a 40-year-old woman with ADHD. She has been prone to forgetfulness since childhood. Two years before visiting our outpatient clinic, she had begun to occasionally forget events that had occurred several days earlier. However, she was largely unaware of the emergence of new amnestic symptoms. She had also begun to experience various other amnestic symptoms 2 months before she visited our clinic, which prompted her to visit our outpatient clinic. The combination of a detailed interview, electroencephalography (EEG) examination, and consideration of TEA enabled us to diagnose her with TEA and provide treatment accordingly. In our patient, daily forgetfulness due to ADHD delayed the recognition of new additional forgetfulness attributed to TEA.<br> Conclusion: Psychiatrists need to consider TEA when patients with ADHD present with changes in or exacerbation of forgetfulness. We report a patient with ADHD who developed TEA. In our patient, daily forgetfulness due to ADHD delayed the recognition of new additional forgetfulness attributed to TEA. Psychiatrists need to consider TEA when patients with ADHD present with changes or exacerbation of forgetfulness. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0264-410X 42 21 2024 Kinetics of SARS-CoV-2 antibody titers after booster vaccinations during an Omicron surge in Japan 126156 EN Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ayako Sasaki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoka Kadowaki 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, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Despite the emergence of SARS-CoV-2 variants and waning immunity after initial vaccination, data on antibody kinetics following booster doses, particularly those adapted to Omicron subvariants like XBB.1.5, remain limited. This study assesses the kinetics of anti-spike protein receptor-binding domain (S-RBD) IgG antibody titers post-booster vaccination in a Japanese population during the Omicron variant epidemic.<br> Methods: A prospective cohort study was conducted in Bizen City, Japan, from November 2023 to January 2024. Participants included residents and workers aged ≥18 years, with at least three COVID-19 vaccinations. Antibody levels were measured from venous blood samples. The study analyzed 424 participants and 821 antibody measurements, adjusting for variables such as age, sex, underlying conditions, and prior infection status. Mixed-effects models were employed to describe the kinetics of log-transformed S-RBD antibody titers.<br> Results: The study found that S-RBD antibody titers declined over time but increased with the number of booster vaccinations, particularly those adapted to Omicron and its subvariant XBB.1.5 (Pfizer-BioNTech Omicron-compatible: 0.156, 95%CI −0.032 to 0.344; Pfizer-BioNTech XBB-compatible: 0.226; 95%CI −0.051 to 0.504; Moderna Omicron-compatible: 0.279, 95%CI 0.012 to 0.546; and Moderna XBB-compatible: 0.338, 95%CI −0.052 to 0.728). Previously infected individuals maintained higher antibody titers, which declined more gradually compared to uninfected individuals (coefficient for interaction with time 0.006; 95%CI 0.001 to 0.011). Sensitivity analyses using Generalized Estimating Equations and interval-censored random intercept model confirmed the robustness of these findings.<br> Conclusions: The study provides specific data on antibody kinetics post-booster vaccination, including the XBB.1.5-adapted vaccine, in a highly vaccinated Japanese population. The results highlight the importance of considering individual demographics and prior infection history in optimizing vaccination strategies. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 4 2024 Effect of Recipient Age on Perioperative Complications after Pediatric Liver Transplantation: A Single-Center Retrospective Study 323 330 EN Akira Katayama Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Kimura Department of Anesthesia, Kyoto University Hospital Takashi Matsusaki Department of Anesthesiology, Mie University Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/67548 It has not been clear how recipient age affects the incidence of serious complications after pediatric living donor liver transplantation (LDLT). We investigated the records of 42 pediatric patients receiving LDLT, dividing our sample into two groups: the infant group (aged < 1 year) and the non-infant group (aged ≥ 1 year and ≤15 years). The primary outcome was postoperative complications assessed using the Clavien-Dindo classification. Multivariate analysis using the Cox regression model was applied to adjust for confounding factors in assessing the incidence of Clavien-Dindo grade ≥ III (C-D ≥ III) complications. The incidence of C-D ≥ III complications was higher in the non-infant group (46.2%) than in the infant group (12.5%) (odds ratio 6.00, 95% confidence interval [CI] 1.13-31.88, p=0.03). In multivariate analysis using the Cox regression model, the Graft-to-Recipient Weight Ratio (GRWR) was independently associated with the incidence of C-D ≥ III complications (hazard ratio [HR] 0.62, 95%CI 0.40-0.95, p=0.03), but being an infant was not (HR 0.84, 95%CI 0.35-1.98, p=0.68). In conclusion, the incidence of C-D ≥ III complications was higher in the non-infant group than in the infant group, but this was largely a function of GRWR: multivariate analysis revealed that GRWR was independently associated with complications. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 4 2024 Can Pelvic Lymph Node Dissection in Prostate Cancer Patients with a 5% Briganti Nomogram Cut-off Value Provide an Oncological Benefit? A Large Multi-Institutional Cohort Study in Japan 307 312 EN Naoya Sugihara Department of Urology, Ehime University Katsuyoshi Hashine Department of Urology, National Hospital Organization Shikoku Cancer Center Natsumi Yamashita Division of Epidemiology, National Hospital Organization Shikoku Cancer Center Miki Sakamoto Department of Urology, Ehime University Masato Terashita Department of Urology, Ehime University Keisuke Funaki Department of Urology, Ehime University Kaori Saiki Department of Urology, Ehime University Takatora Sawada Department of Urology, Ehime University Toshio Kakuda Department of Urology, Ehime University Kenichi Nishimura Department of Urology, Ehime University Tetsuya Fukumoto Department of Urology, Ehime University Noriyosi Miura Department of Urology, Ehime University Yuki Miyauchi Department of Urology, Ehime University Tadahiko Kikugawa Department of Urology, Ehime University Takashi Saika Department of Urology, Ehime University Original Article 10.18926/AMO/67546 The Briganti nomogram (cut-off value 5%) is commonly used to determine the indications for pelvic lymph node dissection (PLND) in patients with prostate cancer. We retrospectively analyzed the potential oncological benefit of PLND based on the 5% cut-off value on the Briganti nomogram. We obtained the data from the Medical Investigation Cancer Network (MICAN) Study, which included 3,463 patients who underwent a radical prostatectomy (RP) at nine institutions in Japan between 2010 and 2020. We included patients with Briganti scores ≥ 5% and a follow-up period ≥6 months and excluded patients categorized in the very high-risk group (based on NCCN categories); a final total of the cases of 1,068 patients were analyzed. The biochemical recurrence (BCR)-free survival was significantly worse in the patients who underwent PLND compared to those who did not (p=0.019). A multivariate analysis showed that high prostate-specific antigen (PSA) levels (p<0.001) and an advanced T-stage (p=0.018) were significant prognostic factors for BCR, whereas PLND had no effect on BCR (p=0.059). Thus, PLND in patients with prostate cancer whose Briganti score was 5% did not provide any oncological benefit. Further research is necessary to determine the indication criteria for conducting PLND. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 13 15 2024 Evolution and Effects of Ad Hoc Multidisciplinary Team Meetings in the Emergency Intensive Care Unit: A Five-Year Analysis 4324 EN Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohei Ageta Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Toshiyuki Aokage Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background: Multidisciplinary team meetings (MDTMs) are crucial in the ICU. However, daily rounds may not address all sensitive issues due to time constraints and the complexity of cases. This study aimed to describe detailed information and characteristics of ad hoc MDTMs in the ICU. Methods: This single-center, retrospective study analyzed adult emergency ICU admissions at Okayama University Hospital from 1 January 2019 to 31 December 2023. During this period, weekly regular multidisciplinary team ICU rounds were introduced in June 2020, and regular weekday morning MDTMs began in April 2022. A multiple logistic regression analysis was applied to determine the impact of these changes on the frequency of ad hoc MDTMs, adjusting for variables including annual changes. Results: The study analyzed 2487 adult EICU patients, with a median age of 66, and 63.3% of them male. MDTMs were held for 168 patients (6.8%), typically those with severe conditions, including higher COVID-19 prevalence and APACHE II scores, and longer ICU stays. Despite a constant total number of MDTMs, the likelihood of conducting ad hoc MDTMs increased annually (adjusted OR 1.19; 95% CI, 1.04-1.35). Of the 329 MDTMs conducted for these patients, 59.0% addressed end-of-life care, involving an average of 11 participants, mainly nurses and emergency and critical-care physicians. Conclusions: Changes in ICU round and meeting structures might be associated with a higher frequency of conducting ad hoc MDTMs, highlighting their evolving role and importance in patient care management. No potential conflict of interest relevant to this article was reported.