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

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

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

Wiley Acta Medica Okayama 0309-0167 88 5 2025 Claudin-18 expression in gastric type adenocarcinoma and HPV-associated adenocarcinoma of the uterine cervix 1003 1015 EN Nobuko Yasutake Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Yuki Yokawa Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Takehiro Tanaka Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Riri Mishima Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Misato Komamizu Department of Gynecology and Obstetrics, Graduate School of Medical Sciences Kyushu University Fukuoka Japan Ryosuke Kuga Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University Rina Jiromaru Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University Shinichiro Kawatoko Department of Medicine and Clinical Science, Kyushu University Beppu Hospital Kenzo Sonoda Department of Gynecology, Kyushu University Beppu Hospital Hideaki Yahata Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Kiyoko Kato Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Yoshinao Oda Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University Hidetaka Yamamoto Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Aims: Claudin-18 (CLDN18) is both a marker for the gastric phenotype and a therapeutic target. However, little is known about its immunoexpression in endocervical adenocarcinomas (ECAs), particularly as detected using the clone 43-14A antibody, or about the gene expression of its isoforms in ECAs. Methods and results: We examined CLDN18, HIK1083, p16 and Rb expression by immunohistochemistry and high-risk human papillomavirus (HR-HPV) mRNA by in situ hybridization (ISH) in 121 ECAs, including 35 HPV-independent adenocarcinomas (gastric type [GAS], n = 24; non-GAS, n = 11) and 86 HPV-associated ECAs. We also analysed mRNA expression of the CLDN18.1 (lung type) and CLDN18.2 (gastric type) isoforms by quantitative polymerase chain reaction (qPCR) in selected cases. CLDN18 positivity was detected in 8/24 (33%) GASs, 0/11 (0%) non-GASs and 2/86 (2%) HPV-associated ECAs, with positivity defined as staining in ≥75% of tumour cells, as in gastric cancer. When a 5% cut-off was used, CLDN18 positivity was detected in 22/24 (92%) GASs, 0/11 (0%) non-GASs and 6/86 (7%) HPV-associated ECAs; CLDN18 expression was thus significantly associated with GAS histology (P < 0.0001). Among the 6 cases of HPV-associated ECAs with CLDN18 expression (ranging from 5% to 80%), the histological patterns included a mix of usual and mucinous features in 4 cases, pure usual type in 1 and villoglandular variant in 1. Otherwise features such as p16 overexpression and the Rb partial loss pattern were consistent with those of HPV-associated ECAs. Six of 22 (27%) CLDN18-positive GASs were also positive for p16, but their other features—such as CLDN18 expression and the Rb preserved pattern—were the same as in p16 negative GASs. Expression of CLDN18.2 mRNA but not CLDN18.1 mRNA was confirmed in both GASs and HPV-associated ECAs. Conclusions: CLDN18 (43-14A) emerged as a potential diagnostic and therapeutic marker for GAS. A minor subset of HPV-associated ECAs also can be immunoreactive for CLDN18 and express CLDN18.2 mRNA, suggesting divergent gastric phenotypic differentiation. The caution is that GAS and HPV-associated ECAs can share overlapping histological features and similar expression of CLDN18 and p16. No potential conflict of interest relevant to this article was reported.

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

岡山大学農学部 Acta Medica Okayama 2186-7755 115 2026 公表学術論文等リスト　2025 13 26 EN 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.

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

MDPI AG Acta Medica Okayama 1999-4893 19 2 2026 A Slide Annotation System with Multimodal Analysis for Video Presentation Review 110 EN Amma Liesvarastranta Haz Department of Information and Communication Systems, Okayama University Komang Candra Brata Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Htoo Htoo Sandi Kyaw Department of Information and Communication Systems, Okayama University Evianita Dewi Fajrianti Human Centric Multimedia Research Laboratory, Department of Informatic and Computer Engineering, Politeknik Elektronika Negeri Surabaya Sritrusta Sukaridhoto Human Centric Multimedia Research Laboratory, Department of Informatic and Computer Engineering, Politeknik Elektronika Negeri Surabaya With the rapid growth of online presentations, there has been an increasing need for efficient review of recorded materials. In typical presentations, speakers verbally elaborate on each slide, providing details not captured in the slides themselves. Automatically extracting and embedding these verbal explanations at their corresponding slide locations can greatly enhance the review process for audiences. This paper presents a Slide Annotation System that employs a robust hybrid two-stage detector to identify slide boundaries, extracts slide text through Optical Character Recognition (OCR), transcribes narration, and employs a multimodal Large Language Model (LLM) to generate concise, context-aware annotations that are added to their corresponding slide locations. For evaluations, the technical performance was validated on five recorded presentations, while the user experience was assessed by 37 participants. The results showed that the system achieved a macro-average 𝐹1 score of 0.879 (𝑆𝐷=0.024, 95% 𝐶𝐼[0.849,0.909]) for slide segmentation and 90.0% accuracy (95% 𝐶𝐼[74.4%,96.5%]) for annotation alignment. Subjective evaluations revealed high annotation validity and usefulness as rated by presenters, and a high System Usability Scale (SUS) score of 80.5 (𝑆𝐷=6.7, 95% 𝐶𝐼[78.3,82.7]). Qualitative feedback further confirmed that the system effectively streamlined the review process, enabling users to locate key information more efficiently than standard video playback. These findings demonstrate the strong potential of the proposed system as an effective automated annotation system. No potential conflict of interest relevant to this article was reported.

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

American Society for Microbiology Acta Medica Okayama 0099-2240 2025 Efficient resuscitation of early-stage viable but non-culturable cells of Vibrio cholerae using treatment with proteolytic enzymes EN Shin-ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mona Ogasawara Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shiho Niwaki Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Rena Sugihara Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Basilua Andre Muzembo Research Institute of Nursing Care for People and Community, University of Hyogo Daisuke Imamura Research Center for Intestinal Health Science, Okayama University Vibrio cholerae, the etiological agent of cholera, is ubiquitous in environmental brackish waters. Exposure to low water temperatures induces the bacterium to enter a viable but non-culturable (VBNC) state. In this study, a stepwise decrease in water temperature to 4°C was found to delay the transition to the non-culturable state compared to an abrupt temperature drop, suggesting that V. cholerae cells partially adapt to low temperatures. V. cholerae VBNC cells maintained at 4°C gradually lost their ability to revert to a culturable state. However, VBNC cells in the early stage of dormancy were efficiently resuscitated following treatment with proteolytic enzymes, including proteinase K. The abundance of culturable V. cholerae cells in brackish estuarine waters was quantified using the most probable number (MPN)–quantitative polymerase chain reaction (qPCR) method. Although culturable cells were undetectable in samples treated with bovine serum albumin, they were estimated at 93 and 1,500 MPN/mL in two water samples collected on different days and pre-incubated with proteinase K. Similarly, the abundance of Vibrio species increased markedly following treatment with this enzyme. Additionally, cells of Vibrio species were enumerated by the plating method using CHROMagar Vibrio plates. Consistent with the results of the MPN–qPCR method, treatment with proteinase K resulted in over a 100-fold increase in colony formation. Collectively, these findings suggest that treatment with proteinase K is effective for resuscitating and quantifying V. cholerae VBNC cells in environmental water samples. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1758-5902 18 1 2025 A Procedural Transhiatal Approach for the Thoracic Para‐Aortic Lymph Node: A Case Report e70066 EN Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasushige Takeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hijiri Matsumoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kento Kawasaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyoshi Kunitomo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The thoracic posterior para-aortic lymph node (TPAN) is classified as an extra-regional lymph node in esophageal cancer, with metastasis indicating poor prognosis. However, some cases with suspected TPAN metastasis may benefit from esophagectomy with lymph node dissection, including TPAN. This report presents the case of a 58-year-old man with upper thoracic esophageal squamous cell carcinoma and suspected simultaneous TPAN metastasis who underwent neoadjuvant chemotherapy followed by thoracoscopic subtotal esophagectomy and procedural transhiatal TPAN dissection. This transhiatal approach provided direct access to the lymph node without additional thoracic incisions, ensuring safe resection in coordination with the assistant and following anatomical landmarks systematically. Pathological examination showed a false-positive TPAN finding, though the patient later developed distant recurrence. Compared with conventional approaches, this transhiatal technique allows for procedural and reproducible lymphadenectomy while minimizing respiratory burden. This case highlights the feasibility of a transhiatal approach for TPAN dissection. No potential conflict of interest relevant to this article was reported.

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

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. 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. 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. 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.

Iron and Steel Institute of Japan Acta Medica Okayama 0915-1559 65 13 2025 Heat Transfer Enhancement by Forming Bridges among Reactive Particles in a Packed Bed Reactor of a Solid-gas Chemical Heat Storage System 2097 2104 EN Koichi Nakaso Faculty of Environmental, Life Natural Science and Technology, Okayama University Kenji Shimada Graduate School of Natural Science and Technology, Okayama University Yasushi Mino Faculty of Environmental, Life Natural Science and Technology, Okayama University Kuniaki Gotoh Faculty of Environmental, Life Natural Science and Technology, Okayama University In this study, the enhancement of the thermal output of solid-gas chemical heat storage systems was investigated. Bridges made of high-thermal conductivity materials were formed among reactive particles by drying a slurry which contained graphite powder as a thermal additive and dispersant in a packed-bed reactor. First, the effect of the volume ratio of the dispersant on effective thermal conductivity was investigated. The optimum volume ratio of dispersant to graphite powder was determined. Furthermore, repetitive bridge formation increased the effective thermal conductivity. Based on these results, we investigated the thermal response of the energy-discharge process. Consequently, the temperature distribution in the radial direction of the reactor decreased owing to the formation of bridges. In addition, the thermal energy generated by the adsorption of water vapor onto the adsorbent was effectively transferred to the reactor wall. The thermal output was estimated based on the experimental results. The thermal output was increased by the formation of bridges. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2467-981X 10 2025 Favorable outcomes of epilepsy with gait-induced seizures after resection of the unilateral supplementary motor area 489 492 EN Satoshi Kodama Department of Neurology, Graduate School of Medicine, The University of Tokyo Naoto Kunii Department of Neurosurgery, Jichi Medical University Yuichiro Shirota Department of Neurology, Graduate School of Medicine, The University of Tokyo Takusei Chou Department of Neurology, Graduate School of Medicine, The University of Tokyo Mizuho Kawai Department of Neurology, Graduate School of Medicine, The University of Tokyo Seijiro Shimada Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo Meiko Maeda 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 Masashi Hamada Department of Neurology, Graduate School of Medicine, The University of Tokyo Masako Ikemura Department of Pathology, Graduate School of Medicine, The University of Tokyo Yuko Saito Department of Neuropahtology (Brain Bank for Aging Research), Tokyo Metropoliran Institute for Geriatrics and Gerontology Naoki Akamatsu Department of Neurology, International University of Health and Walfare Narita Hospital Taira Uehara Department of Neurology, International University of Health and Walfare Narita Hospital Nobuhito Saito Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Background: Gait-induced seizures are a rare manifestation of reflex epilepsy. Pathophysiology of this phenomenon has not been fully understood. Case presentation: A 28-year-old woman presented with a long history of “falls” following paroxysmal bilateral leg stiffness triggered by walking. Scalp electroencephalogram (EEG) revealed low-amplitude rhythmic beta activity, maximal at the Cz electrode, during these events. Magnetoencephalography demonstrated repetitive sharp waves source-localized to the right primary motor cortex. Multiple anti-seizure medications failed to improve her symptoms; however, the clinical manifestation was consistent with epilepsy with gait-induced seizures. Intracranial subdural EEG recording was performed and confirmed ictal activity originating from the right supplementary motor area. Resection of this area resulted in complete resolution of her symptoms. Discussion: This is the first reported case of successful resective surgery for epilepsy with gait-induced seizure. Brain networks involving cortical regions responsible for the initiation or execution of walking presumably played a key role in the generation of gait-induced seizures. Careful assessment using non-invasive neurophysiological studies facilitated accurate diagnosis, successful intracranial recordings, and effective resective surgery. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0032-0889 198 1 2025 Role of polar localization of the silicon transporter OsLsi1 in metalloid uptake by rice roots kiaf196 EN Noriyuki Konishi Institute of Plant Science and Resources, Okayama University Namiki Mitani-Ueno Institute of Plant Science and Resources, Okayama University Jian Feng Ma Institute of Plant Science and Resources, Okayama University Low silicon (Si) rice 1 (OsLsi1) is a key transporter mediating Si uptake in rice (Oryza sativa). It is polarly localized at the distal side of the root exodermis and endodermis. Although OsLsi1 is also permeable to other metalloids, such as boron (B), germanium (Ge), arsenic (As), antimony (Sb), and selenium (Se), the role of its polar localization in the uptake of these metalloids remains unclear. In this study, we investigated the role of OsLsi1 polar localization in metalloid uptake by examining transgenic rice plants expressing polarly or nonpolarly localized OsLsi1 variants. Loss of OsLsi1 polar localization resulted in decreased accumulation of Ge, B, and As in shoots but increased Sb accumulation, while Se accumulation remained unaffected under normal conditions. Experiments with varying B concentrations revealed that B uptake is significantly lower at low B concentrations (0.3 to 3 μm) but higher at high B concentrations (300 μm) in plants expressing nonpolarly localized OsLsi1, despite the similar B permeability of both OsLsi1 variants in Xenopus oocytes and their comparable protein abundance in roots. Additionally, the loss of OsLsi1 polarity did not affect the abundance, localization, or high B-induced degradation of the borate transporter 1 (OsBOR1), an efflux transporter that cooperates with OsLsi1 for B uptake. Taken together, our findings demonstrate that the polar localization of OsLsi1 plays a critical role in regulating metalloid uptake, depending on the presence or absence of efflux transporters cooperating with OsLsi1. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2772-3755 11 2025 Robustness of the RGB image-based estimation for rice above-ground biomass by utilizing the dataset collected across multiple locations 100998 EN Kota Nakajima Graduate School of Agriculture, Kyoto University Kazuki Saito International Rice Research Institute (IRRI) Yasuhiro Tsujimoto Japan International Research Center for Agricultural Sciences Toshiyuki Takai Japan International Research Center for Agricultural Sciences Atsushi Mochizuki CHIBA Prefectural Agriculture and Forestry Research Center Tomoaki Yamaguchi Faculty of Applied Biological Sciences, Gifu University Ali Ibrahim Africa Rice Center (AfricaRice), Regional Station for the Sahel Salifou Goube Mairoua Africa Rice Center (AfricaRice) Bruce Haja Andrianary Laboratoire des Radioisotopes, Université d′Antananarivo Keisuke Katsura Graduate School of Agriculture, Kyoto University Yu Tanaka Graduate School of Environment, Life, Natural Science and Technology, Okayama University Above-ground biomass (AGB) is a critical phenotype representing crop growth. Non-invasive evaluations of AGB, including deep-learning-based red-green-blue (RGB) image analyses, are often specific to the training data. The robustness of the estimation model across untrained conditions is essential to monitor crop productivity globally, but it has yet to be fully assessed. This study aims to assess the robustness of a convolutional neural network (CNN) model for rice AGB estimation across five locations in three countries, and to demonstrate the feasibility of robust model via a practical approach. From transplanting to heading, 1957 RGB images were captured vertically downward over the rice canopy, covering approximately 1 m2. First, a base model was established using data collected from a single location. Then, its robustness was assessed using test datasets taken from the other four locations. The CNN model showed a significant variation in estimation accuracy across the untrained four locations, indicating insufficient robustness of the base model. Subsequently, we quantitatively tested the impact of improving training data diversity on model robustness by adding data from each of the four locations to the base model's training data. Adding at most 48 data points from a location achieved practical accuracy for the added location, with R2Ad above 0.8. Interestingly, adding data from one location sometimes improved the accuracy for other untrained locations as well. These findings suggest that collecting diverse training data for RGB-based estimation, combined with evaluation of robustness paves the way for on-site and instant AGB monitoring of rice. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1340-2838 32 6 2025 MedakaBase as a unified genomic resource platform for medaka fish biology dsaf030 EN Kenji Morikami Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems Yasuhiro Tanizawa Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems Masaru Yagura Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems Mika Sakamoto Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems Shoko Kawamoto Department of Genetics, Sokendai (Graduate University for Advanced Studies) Yasukazu Nakamura Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems Katsushi Yamaguchi Trans-Omics Facility, National Institute for Basic Biology Shuji Shigenobu Trans-Omics Facility, National Institute for Basic Biology Kiyoshi Naruse Laboratory of Bioresources, National Institute for Basic Biology, National Institutes of Natural Sciences Satoshi Ansai Ushimado Marine Institute, Okayama University Shigehiro Kuraku Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems Medaka, a group of small, mostly freshwater fishes in the teleost order Beloniformes, includes the rice fish Oryzias latipes, a useful model organism studied in diverse biological fields. Chromosome-scale genome sequences of the Hd-rR strain of this species were obtained in 2007, and its improved version has facilitated various genome-wide studies. However, despite its widespread utility, omics data for O. latipes are dispersed across various public databases and lack a unified platform. To address this, the medaka section of the National Bioresource Project (NBRP) of Japan established a genome informatics team in 2022 tasked with providing various in silico solutions for bench biologists. This initiative led to the launch of MedakaBase (https://medakabase.nbrp.jp), a web server that enables gene-oriented analysis including exhaustive sequence similarity searches. MedakaBase also provides on-demand browsing of diverse genome-wide datasets, including tissue-specific transcriptomes and intraspecific genomic variations, integrated with gene models from different sources. Additionally, the platform offers gene models optimized for single-cell transcriptome analysis, which often requires coverage of the 3′ untranslated region (UTR) of transcripts. Currently, MedakaBase provides genome-wide data for seven Oryzias species, including original data for O. mekongensis and O. luzonensis produced by the NBRP team. This article outlines technical details behind the data provided by MedakaBase. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1479-5876 23 1 2025 Tumor marker–guided precision BNCT for CA19-9–positive cancers: a new paradigm in molecularly targeted chemoradiation therapy 1387 EN Noriyuki Kanehira Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Tajima Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tatsunori Osone Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Takuya Fujimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Sakurai Institute for Integrated Radiation and Nuclear Science, Kyoto University Natsuko Kondo Institute for Integrated Radiation and Nuclear Science, Kyoto University Narikazu Nagahisa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaoru Kamei Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Taiga Fujita Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Akira Morihara Graduate School of Environmental, Life Science, Okayama University Yutaka Takaguchi Faculty of Sustainable Design, Department of Material Design and Engineering, University of Toyama Mizuki Kitamatsu Department of Applied Chemistry, Kindai University Takeshi Takarada Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Minoru Suzuki Institute for Integrated Radiation and Nuclear Science, Kyoto University Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Michiue Neutron Therapy Research Center, Okayama University Background: Boron neutron capture therapy (BNCT) is a molecularly targeted chemoradiation modality that relies on boron delivery agents such as p-borophenylalanine (BPA), which require LAT1 (L-type amino acid transporter 1) for tumor uptake. However, the limited efficacy of BPA in LAT1-low tumors restricts its therapeutic scope. To address this limitation, we developed a tumor marker–guided BNCT strategy targeting cancers overexpressing the clinically validated glycan biomarker CA19-9. Methods: We conducted transcriptomic analyses using The Cancer Genome Atlas (TCGA) datasets to identify LAT1-low cancers with high CA19-9 expression. These analyses revealed elevated expression of fucosyltransferase 3 (FUT3), which underlies CA19-9 biosynthesis, in pancreatic, biliary, and ovarian malignancies. Based on this, we synthesized a novel boron compound, fucose-BSH, designed to selectively accumulate in CA19-9–positive tumors. We evaluated its physicochemical properties, pharmacokinetics, biodistribution, and antitumor efficacy in cell lines and xenograft models, comparing its performance to that of BPA. Results: Fucose-BSH demonstrated significantly greater boron uptake in CA19-9–positive cell lines (AsPC-1, Panc 04.03, HuCCT-1, HSKTC, OVISE) compared to CA19-9–negative PANC-1. In HuCCT-1 xenografts, boron accumulation reached 36.2 ppm with a tumor/normal tissue ratio of 2.1, outperforming BPA. Upon neutron irradiation, fucose-BSH–mediated BNCT achieved > 80% tumor growth inhibition. Notably, fucose-BSH retained therapeutic efficacy in LAT1-deficient models where BPA was ineffective, confirming LAT1-independent targeting. Conclusions: This study establishes a novel precision BNCT approach by leveraging CA19-9 as a tumor-selective glycan marker for boron delivery. Fucose-BSH offers a promising platform for expanding BNCT to previously inaccessible LAT1-low malignancies, including pancreatic, biliary, and ovarian cancers. These findings provide a clinically actionable strategy for tumor marker–driven chemoradiation and lay the foundation for translational application in BNCT. This strategy has the potential to support companion diagnostic development and precision stratification in ongoing and future BNCT clinical trials. Translational Relevance: Malignancies with elevated CA19-9 expression, such as pancreatic, biliary, and ovarian cancers, are associated with poor prognosis and limited response to current therapies. This study presents a tumor marker–guided strategy for boron neutron capture therapy (BNCT) by leveraging CA19-9 glycan biology to enable selective tumor targeting via fucose-BSH, a novel boron compound. Through transcriptomic data mining and preclinical validation, fucose-BSH demonstrated LAT1-independent boron delivery, potent BNCT-mediated cytotoxicity, and tumor-specific accumulation in CA19-9–positive models. These findings support a precision chemoradiation approach that addresses a critical gap in BNCT applicability, offering a clinically actionable pathway for patient stratification and therapeutic development in CA19-9–expressing cancers. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2050-6511 26 1 2025 PEGylation of liposome-encapsulated midazolam does not improve the bioavailability of midazolam when administered orally 166 EN Yukiko Nishioka Department of Dental Anesthesiology, Okayama University Hospital Yanyin Lu Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitoshi Higuchi Department of Dental Anesthesiology, Okayama University Hospital Saki Miyake Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Maki Fujimoto Department of Dental Anesthesiology, Okayama University Hospital Midori Hamaoka-Inoue Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tanimura Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitomi Ujita Department of Dental Anesthesiology, Okayama University Hospital Shigeru Maeda Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Miyawaki Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Liposomes are closed vesicles made of the same phospholipid bilayer as biological membranes and are capable of containing drugs, and so they have been investigated as useful drug carriers for drug delivery. We previously developed liposome-encapsulated midazolam (LE-midazolam) for oral administration, but midazolam is metabolized in the liver, and for clinical use the encapsulation of the liposomes needed to be improved to increase the bioavailability of midazolam. The surfaces of pharmaceutical liposomes are generally coated with polyethylene glycol (PEGylation) because it prevents their capture by phagocytes and helps them to avoid the reticuloendothelial system. Therefore, we considered that PEGylation could reduce the metabolism of orally administered encapsulated midazolam in the liver. Methods Midazolam solution, LE-midazolam solution, and PEGylated liposome-encapsulated midazolam (PEG-LE-midazolam) solution were prepared, and the characteristics of the liposomes in these solutions were evaluated. Furthermore, these solutions were orally administered to rabbits, and the resultant plasma midazolam concentrations were measured. The effects of the PEGylation of LE-midazolam on the plasma concentration and bioavailability of orally administered midazolam were also evaluated. Results The PEG-LE-midazolam solution contained a higher percentage of larger liposomes than the LE-midazolam solution. The area under the concentration-time curve (AUC) of the LE-midazolam solution was significantly higher than that of the midazolam solution, but there was no difference between the AUC values of the PEG-LE-midazolam and midazolam solutions. Conclusions These findings suggest that liposome encapsulation may reduce the first-pass effect following oral administration, but PEGylation is not expected to improve the bioavailability of orally administered midazolam. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Morphological/developmental characteristics and oxidative stress resilience of porcine oocytes derived from antral follicles with various diameters and classified by brilliant cresyl blue staining EN VAN NGOC PHONG Graduate School of Environmental and Life Science, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Impacts of Dental Follicle Cells and Periodontal Ligament Cells on the Bone Invasion of Well-Differentiated Oral Squamous Cell Carcinoma EN ANQI CHANG Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Tumor microvessels with specific morphology as a prognostic factor in esophageal squamous cell carcinoma EN HNIN THIDA TUN Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Cancer‑associated fibroblasts promote pro‑tumor functions of neutrophils in pancreatic cancer via IL‑8: potential suppression by pirfenidon EN Tomohiko YAGI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) with voluntary and forced exercise in a rat model of ischemic stroke EN Takayuki NAGASE Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 17 17 2025 Refining the Role of Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma 2770 EN Kiyofumi Takabatake Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Piao Tianyan Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuma Arashima Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Anqi Chang Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Htoo Shwe Eain Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yamin Soe Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Zin Zin Min Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masae Fujii Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University In the tumor microenvironment, various immune and stromal cells, such as fibroblasts and vascular endothelial cells, contribute to tumor growth and progression by interacting with cancer cells. Tumor-associated macrophages (TAMs) have attracted attention as major players in the tumor microenvironment. The origin of TAMs is believed to be the infiltration of monocytes derived from bone marrow progenitor cells into tumor tissues and their differentiation into macrophages, whereas tissue-resident macrophages derived from yolk sacs have recently been reported. TAMs infiltrating tumor tissues act in a tumor-promoting manner through immunosuppression, angiogenesis, and the promotion of cancer cell invasion. Reflecting the nature of TAMs, increased TAM invasion and TAM-specific gene expression in tumor tissues may be the new biomarkers for cancer. Moreover, new therapeutic strategies targeting TAMs, such as transformation into immunostimulatory macrophages, suppression of TAM infiltration, and promotion of phagocytosis, are being investigated, and many clinical trials are underway. As the origin and function of TAMs are further elucidated, TAM-targeted therapy is expected to become a new option for the immunotherapy of various cancers, including oral cancers. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2590-1230 27 2025 Voxel-based method for predicting workpiece chipping in end milling of unsintered pure iron-powder compact 106656 EN Hiroto Takayasu Graduate School of Science and Engineering, Ibaraki University Kazuki Kaneko Graduate School of Environmental and Life Science, Okayama University Jun Shimizu Graduate School of Science and Engineering, Ibaraki University The miniaturization and high-torque requirements of electric motors in automotive and industrial applications have increased the adoption of axial-gap motors that employ unsintered pure iron-powder compacts. However, machining these brittle materials, particularly through end milling, typically results in significant workpiece chipping, which impedes cost-effective prototyping and small-lot production. Conventional chipping-prediction approaches, such as finite-element analysis and critical uncut chip-thickness methods, are limited by their computational costs and prediction accuracy, respectively. This study proposes a novel method for predicting chipping regions in the end milling of pure iron-powder compacts via voxel-based cutting-force simulation. The chipping risk at each voxel was evaluated based on the magnitude and direction of the simulated cutting force and local workpiece rigidity. Chipping was predicted when the risk index exceeded the threshold value. Cutting experiments were conducted to validate the proposed method, which shows good agreement between the predicted and observed chipping regions under various milling conditions. The results indicate that the proposed method can efficiently and accurately predict the chipping regions, thus outperforming conventional approaches in terms of computational cost. Although parameter tuning and threshold calibration were performed experimentally, the voxel-based framework enables practical prediction and analysis of transient machining phenomena. Future investigations shall focus on expanding the method to a wider range of machining conditions and integrating material-property considerations for further generalization. This approach offers a practical tool for optimizing machining parameters to minimize chipping and enhance the manufacturability of brittle powder compacts. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0014-4886 386 2025 Therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) with voluntary and forced exercise in a rat model of ischemic stroke 115145 EN Takayuki Nagase Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takao Yasuhara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kyohei Kin Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Sasada Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Kawauchi Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Yabuno Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiaki Sugahara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuichi Hirata Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hayato Miyake Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsuya Sasaki Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Kawai Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shun Tanimoto Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoya Saijo Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ischemic stroke results in significant long-term disability and mortality worldwide. Although existing therapies, such as recombinant tissue plasminogen activator and mechanical thrombectomy, have shown promise, their application is limited by stringent conditions. Mesenchymal stem cell (MSC) transplantation, especially using SB623 cells (modified human bone marrow-derived MSCs), has emerged as a promising alternative, promoting neurogenesis and recovery. This study evaluated the effects of voluntary and forced exercise, alone and in combination with SB623 cell transplantation, on neurological and psychological outcomes in a rat model of ischemic stroke. Male Wistar rats that had undergone middle cerebral artery occlusion (MCAO) were divided into six groups: control, voluntary exercise (V-Ex), forced exercise (F-Ex), SB623 transplantation, SB623 + V-Ex, and SB623 + F-Ex. Voluntary exercise was facilitated using running wheels, while forced exercise was conducted on treadmills. Neurological recovery was assessed using the modified neurological severity score (mNSS). Psychological symptoms were evaluated through the open field test (OFT) and forced swim test (FST), and neurogenesis was assessed via BrdU labeling. Both exercise groups exhibited significant changes in body weight post-MCAO. Both exercises enhanced the treatment effect of SB623 transplantation. The forced exercise showed a stronger treatment effect on ischemic stroke than voluntary exercise alone, and the sole voluntary exercise improved depression-like behavior. The SB623 + F-Ex group demonstrated the greatest improvements in motor function, infarct area reduction, and neurogenesis. The SB623 + V-Ex group was most effective in alleviating depression-like behavior. Future research should optimize these exercise protocols and elucidate the underlying mechanisms to develop tailored rehabilitation strategies for stroke patients. 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.

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

American Society for Microbiology Acta Medica Okayama 0022-538X 99 10 2025 Human herpesvirus 6B U65 binds to histone proteins and suppresses interferon production e00984-25 EN Haokun Li Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirohito Ogawa Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Da Teng Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Okame Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hikaru Namba Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoyuki Honda Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Human herpesvirus 6B (HHV-6B), a member of the Betaherpesvirinae subfamily, is a T-lymphotropic virus that causes exanthem subitum and has been implicated in neuroinflammatory conditions such as multiple sclerosis. The tegument proteins, which are characteristic of herpesviruses, play a crucial role in the envelopment of virions and evasion of host immune defenses, such as the interferon β (IFNβ) signaling pathway. However, the precise mechanisms through which the HHV-6B tegument proteins modulate the IFNβ pathway are not yet fully understood. In this study, we identified a novel function of the HHV-6B tegument protein U65 as an inhibitor of IFNβ production. Additionally, two host histone proteins, hCG_2039566 (H2ACG) and H2AC7, were identified as positive regulators of innate immune pathways. U65 interacts with H2ACG and H2AC7, impairing their ability to promote the IFNβ pathway. Furthermore, we demonstrated that U65 plays critical roles during HHV-6B infection. This study highlights a critical strategy employed by HHV-6B to evade immune defenses, shedding light on its mechanisms for counteracting host responses. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2075-1729 15 11 2025 Kidney Organoids: Current Advances and Applications 1680 EN Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naruhiko Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Haraguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinji Kitamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kidney organoids, derived from stem cells, including pluripotent stem cells and adult progenitor cells, have been reported as three-dimensional in vitro models that reflect key aspects of kidney development, structure, and function. Advances in differentiation protocols and tissue engineering have enabled the generation of organoids that exhibit nephron-like structures, including glomerular and tubular structures. Kidney organoids have been widely applied in several directions, including disease modeling and therapeutic screening, drug nephrotoxicity evaluation, and regenerative medicine. In particular, kidney organoids offer a promising platform for studying genetic kidney diseases, such as polycystic kidney disease and congenital anomalies of the kidney and urinary tract (CAKUT), by allowing patient-specific modeling for the analysis of pathophysiology and therapeutic screening. Despite several current limitations, such as incomplete maturation, lack of full nephron segmentation, and variability between protocols and cell conditions, further technological innovations such as microfluidics and bioengineering may refine kidney organoid systems. This review highlights recent advances in kidney organoid research, outlines major applications, and discusses future directions to enhance their physiological relevance, functional maturity, and translational integration into preclinical and clinical nephrology. No potential conflict of interest relevant to this article was reported.

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.

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

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 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. Methods 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. Results 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. Discussion 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.

Springer Science and Business Media LLC Acta Medica Okayama 1434-3916 145 1 2025 Component placement angles in total knee arthroplasty affect mid- to long-term clinical results: an average 8-year follow-up study 457 EN Koki Kawada Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Yokoyama Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomonori Tetsunaga Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuki Yamada Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Okazaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiki Kohara 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 Few studies have examined how the component placement angles in total knee arthroplasty (TKA) affect mid- to long-term clinical outcomes. This study investigated the influence of coronal and sagittal plane component placement angles on mid- to long-term outcomes in mechanical alignment TKA. Materials and Methods Forty-eight knees undergoing TKA using the FINE Total Knee System were evaluated for range of motion (ROM) preoperatively. Both ROM and clinical scores were evaluated at 3 and 5 years postoperatively and at the final follow-up (average 8-year). The valgus (alpha) and flexion (gamma) angles of the femoral component, and the varus (beta) and posterior tilt (sigma) angles of the tibial component were evaluated. Correlations between radiographic assessments, knee ROM, and clinical scores were assessed using Spearman's correlation coefficient. Results The alpha angle was negatively correlated with the knee flexion angle (r = − 0.323, p = 0.025) and ROM (r = − 0.352, p = 0.014), and the sigma angle was negatively correlated with the Knee Injury and Osteoarthritis Outcome Score (KOOS)-Symptoms at 3 years postoperatively (r = − 0.304, p = 0.036). The alpha angle was negatively correlated with the knee flexion angle (r = − 0.357, p = 0.013), ROM (r = − 0.337, p = 0.019), and KOOS-Sports and Recreation function (r = − 0.349, p = 0.015), and positively correlated with the Visual Analog Scare pain score (r = 0.307, p = 0.034) at the final follow-up. The beta angle was positively correlated with KOOS-Pain (r = 0.303, p = 0.036) and KOOS-Symptoms (r = 0.397, p = 0.005) at the final follow-up. Conclusions Valgus placement of the femoral component and varus placement of the tibial component in the FINE Total Knee System negatively impacted clinical scores at an average 8-year follow-up. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0962-8819 34 1 2025 Highly efficient transgenesis mediated by Tip100 transposon system in medaka 46 EN Yoshitaka Tanaka Ushimado Marine Institute (UMI), Okayama University Takahide Seki Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University Atsushi Hoshino National Institute for Basic Biology Satoshi Ansai Ushimado Marine Institute (UMI), Okayama University Transgenesis mediated by transposon is an effective approach for introducing exogenous DNA into the nuclear genome and establishing stable transgenic strains that efficiently express genetic tools. Although the DNA transposon Tol2 is widely used for transgenesis in zebrafish, its endogenous transpositional activity can lead to unintended transgene mobilization, making it unsuitable for transgenesis in medaka (Oryzias latipes). Here, we demonstrated that the DNA transposon Tip100, originally identified in the common morning glory (Ipomoea purpurea), an ornamental plant, can serve as a useful tool for transgenesis in Japanese medaka. The GFP transgene cassette, when co-injected with Tip100 transposase mRNA, was expressed in significantly higher number of somatic cells in the injected fish. Furthermore, a transgene flanked by truncated recognition sequences (100 bp each) exhibited expression levels comparable to those of the original vector containing the full 2.2 kb recognition sequence. Injection of a transgene driven by a germline-specific promoter revealed that fish injected with Tip100 mRNA exhibited a significantly higher germline transmission rate (42/68; 62.7%) compared to those injected without the mRNA (13/62; 21.0%). We successfully established transgenic strains by outcrossing injected founders with GFP-positive germ cells (7/7; 100%) and demonstrated that the transgenes were randomly integrated into the medaka genome, generating 8-bp duplications at the insertional sites–an insertional signature of the hAT superfamily of transposons. Our findings indicate that the Tip100 system is a promising tool for generating stable transgenic strains that express various genetic tools in medaka and potentially other fish species. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 25 21 2024 Dennd2c Negatively Controls Multinucleation and Differentiation in Osteoclasts by Regulating Actin Polymerization and Protrusion Formation 11479 EN Yu Koyanagi Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University Eiko Sakai Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University Yu Yamaguchi Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University Fatima Farhana Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University Yohsuke Taira Division of Cariology and Restorative Dentistry, Department of Prosthetic Dentistry, Graduate School of Biomedical Sciences, Nagasaki University Kuniaki Okamoto Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Murata Division of Cariology and Restorative Dentistry, Department of Prosthetic Dentistry, Graduate School of Biomedical Sciences, Nagasaki University Takayuki Tsukuba Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University Osteoclasts are bone-resorbing multinucleated giant cells formed by the fusion of monocyte/macrophage lineages. Various small GTPases are involved in the multinucleation and differentiation of osteoclasts. However, the roles of small GTPases regulatory molecules in osteoclast differentiation remain unclear. In the present study, we examined the role of Dennd2c, a putative guanine nucleotide exchange factor for Rab GTPases, in osteoclast differentiation. Knockdown of Dennd2c promoted osteoclast differentiation, resorption, and expression of osteoclast markers. Morphologically, Dennd2c knockdown induced the formation of larger osteoclasts with several protrusions. In contrast, overexpression of Dennd2c inhibited the multinucleation and differentiation of osteoclasts, bone resorption, and the expression of osteoclast markers. Dennd2c-overexpressing macrophages exhibited spindle-shaped mononuclear cells and long thin protrusions. Treatment of Dennd2c-overexpressing cells with the Cdc42 inhibitor ML-141 or the Rac1 inhibitor 6-thio-GTP prevented protrusion formation. Moreover, treatment of Dennd2c-overexpressing cells with the actin polymerization inhibitor latrunculin B restored multinucleated and TRAP-positive osteoclast formation. These results indicate that Dennd2c negatively regulates osteoclast differentiation and multinucleation by modulating protrusion formation in macrophages. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 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. 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. 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. 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.

Oxford University Press (OUP) Acta Medica Okayama 1743-6095 2025 Dual-action intranasal oxytocin enhances both male sexual performance and fertility in rats 1 3 EN Chica Enomoto Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takumi Oti Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takahiro Yamanaka Laboratory of Reproductive Endocrinology, Graduate School of Integrated Sciences for Life, Hiroshima University Masayuki Shimada Laboratory of Reproductive Endocrinology, Graduate School of Integrated Sciences for Life, Hiroshima University Hirotaka Sakamoto Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 0258-851X 39 5 2025 The Geriatric Nutritional Risk Index: A Key Indicator of Perioperative Outcome in Oldest-old Patients With Colorectal Cancer 2810 2817 EN FUMINORI TERAISHI Department of Gastroenterological Surgery, Okayama University Hospital MASASHI UTSUMI Department of Surgery, National Hospital Organization Fukuyama Medical Center YUSUKE YOSHIDA Department of Gastroenterological Surgery, Okayama University Hospital RYOHEI SHOJI Department of Gastroenterological Surgery, Okayama University Hospital NOBUHIKO KANAYA Department of Gastroenterological Surgery, Okayama University Hospital YUKI MATSUMI Department of Gastroenterological Surgery, Okayama University Hospital KUNITOSHI SHIGEYASU Department of Gastroenterological Surgery, Okayama University Hospital YOSHITAKA KONDO Department of Gastroenterological Surgery, Okayama University Hospital SHIORI ITAGAKI Perioperative Management Center, Okayama University Hospital RIE TAMURA Perioperative Management Center, Okayama University Hospital YOSHIKAZU MATSUOKA Perioperative Management Center, Okayama University Hospital TOSHIYOSHI FUJIWARA Department of Gastroenterological Surgery, Okayama University Hospital MASARU INAGAKI Department of Surgery, National Hospital Organization Fukuyama Medical Center Background/Aim: Colorectal cancer (CRC) presents a significant challenge in oldest-old patients (≥85 years), where surgical intervention carries substantial perioperative risks. Nutritional status is a crucial determinant of outcomes, and the Geriatric Nutritional Risk Index (GNRI) has shown promise. This prospective study aimed to validate the GNRI as a key indicator of perioperative outcomes in oldest-old patients undergoing CRC surgery, and to establish its utility in preoperative risk stratification. Patients and Methods: This prospective study enrolled patients aged ≥85 years undergoing elective surgery for CRC. Preoperative GNRI was calculated using the formula: GNRI=14.89×serum albumin (g/dl)+41.7×[actual body weight/ideal body weight (corresponding to body mass index 22)]. Patients were stratified into two groups: GNRI >98 and GNRI ≤98. Baseline demographics, clinical characteristics, geriatric assessments (including Geriatric-8 and EuroQol 5 dimension), and postoperative complication rates were analyzed. Results: Twenty-four patients (median age 88 years, interquartile range=86-91) were included: 11 in the GNRI >98 group and 13 in the GNRI ≤98 group. The patients with GNRI >98 demonstrated significantly better G8 scores (median 12 vs. 11, p<0.01) and EQ-5D index values (median 88 vs. 75.0, p<0.01). The postoperative complication rate was significantly higher in the GNRI ≤98 group (p=0.02). Conclusion: Preoperative GNRI effectively identifies oldest-old patients with CRC at increased risk for postoperative complications. A GNRI ≤98 correlates with poorer nutritional status and impaired geriatric functional parameters. These findings highlight GNRI’s utility as a simple, valuable tool for preoperative risk stratification, potentially guiding interventions to optimize outcomes in this vulnerable population. No potential conflict of interest relevant to this article was reported.

Institute of Electrical and Electronics Engineers (IEEE) Acta Medica Okayama 2169-3536 13 2025 Security in Post-Quantum Era: A Comprehensive Survey on Lattice-Based Algorithms 89003 89024 EN Hien Nguyen School of Informatics, Computing, and Cyber Systems, Northern Arizona University Samsul Huda Interdisciplinary Education and Research Field, Okayama University Yasuyuki Nogami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tuy Tan Nguyen School of Informatics, Computing, and Cyber Systems, Northern Arizona University Lattice-based post-quantum cryptography (PQC) has attracted significant attention as a promising solution to the security challenges posed by quantum computing. Unlike traditional cryptographic algorithms, lattice-based schemes are expected to remain secure even in the presence of quantum attacks, making them essential for securing future data. Despite their strong theoretical foundations, lattice-based schemes face several practical challenges, particularly in optimizing performance and scalability for real-world applications. This survey provides a novel taxonomy that categorizes lattice-based PQC designs, with an emphasis on computational paradigms and security considerations. We systematically evaluate lattice-based PQC implementations across both software platforms, including central processing units and graphics processing units, as well as hardware platforms like field-programmable gate arrays and application-specific integrated circuits, highlighting their strengths and limitations. In addition, we explore the practical applications of lattice-based cryptography in fields such as secure communication, critical infrastructure, privacy-preserving data analytics, artificial intelligence, and trust and authentication systems. By offering a comprehensive overview of the current state of lattice-based PQC, this survey aims to provide valuable insights into the ongoing advancements and future research directions in the field as we transition to a post-quantum era. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2667-2421 18 2025 Postnatal expression of Cat-315-positive perineuronal nets in the SAMP10 mouse primary somatosensory cortex 244 256 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Eriko Kitano Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Perineuronal nets (PNNs) form at the end of the critical period of plasticity in the mouse primary somatosensory cortex. PNNs are said to have functions that control neuroplasticity and provide neuroprotection. However, it is not clear which molecules in PNNs have these functions. We have previously reported that Cat-315-positive molecules were not expressed in the PNNs of the senescence-accelerated model (SAM)P10 strain model mice at 12 months of age. To confirm whether the loss of Cat-315-positive molecules occurred early in life in SAMP10 mice, we examined Cat-315-positive PNNs in the primary somatosensory cortex during postnatal development. This research helps to elucidate the function of PNNs and the mechanism of cognitive decline associated with ageing. To confirm whether Cat-315-positive PNNs changed in an age-dependent manner in SAMP10 mice, we examined the primary somatosensory cortex at 21, 28, and 56 days after birth. We compared these results with those of senescence-accelerated mouse-resistant (SAMR) mice. In SAMP10 mice, Cat-315-positive PNNs were expressed in the primary somatosensory cortex early after birth, but their expression was significantly lower than that in SAMR1 mice. Many other molecules that calibrated the PNN were unchanged between SAMP10 and SAMR1 mice. This study revealed that the expression of the Cat-315 epitope was decreased in the primary somatosensory cortex of SAMP10 mice during postnatal development. SAMP10 mice have had histological abnormalities in their brains since early life. Furthermore, using SAMP10 will be useful in elucidating the mechanism of age-related abnormalities in brain function as well as in elucidating the function and structure of PNNs. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2227-9032 13 12 2025 Association Between Chewing Status and Steatotic Liver Disease in Japanese People Aged ≥50 Years: A Cohort Study 1399 EN Komei Iwai Department of Community Oral Health, School of Dentistry, Asahi University Daisuke Ekuni Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuji Azuma Department of Community Oral Health, School of Dentistry, Asahi University Takatoshi Yonenaga Department of Community Oral Health, School of Dentistry, Asahi University Koichiro Tabata Department of Community Oral Health, School of Dentistry, Asahi University Naoki Toyama Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kota Kataoka Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Maruyama Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaaki Tomofuji Department of Community Oral Health, School of Dentistry, Asahi University Background/Objectives: In this longitudinal study, the relationship between chewing status and steatotic liver disease (SLD) was examined in 3775 people aged ≥50 years who underwent medical checkups at Junpukai Health Maintenance Center in Okayama, Japan. Methods: Participants without SLD at the time of a baseline survey in 2018 were followed until 2022. Chewing status was assessed by a self-administered questionnaire. The presence or absence of SLD was ascertained from the medical records of Junpukai Health Maintenance Center. Results: A total of 541 participants (14%) were diagnosed as having a poor chewing status at baseline. Furthermore, 318 (8%) participants were newly diagnosed with SLD at follow-up. In multivariate logistic regression analyses, the presence or absence of SLD was found to be associated with the following characteristics at baseline: sex (male: odds ratio [ORs] = 1.806; 95% confidence interval [CIs]: 1.399–2.351), age (ORs = 0.969; 95% CIs: 0.948–0.991), body mass index (≥25.0 kg/m2; ORs = 1.934; 95% CIs: 1.467–2.549), diastolic blood pressure (ORs = 1.017; 95% CIs: 1.002–1.032), and chewing status (poor: ORs = 1.472; 95% CIs: 1.087–1.994). Conclusions: The results indicate that a poor chewing status was associated with SLD development after 4 years. Aggressively recommending dental visits to participants with poor chewing status may not only improve their ability to chew well but may also reduce the incidence of SLD. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 17 15 2025 The Concept of “Platinum Sensitivity” in Endometrial Cancer 2557 EN Shoji Nagao Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsushi Fujikawa Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryoko Imatani Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinori Tani Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirofumi Matsuoka Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoyuki Ida Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junko Haraga Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chikako Ogawa Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichiro Nakamura Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hisashi Masuyama Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The concept of “platinum sensitivity” has long guided prognostic assessment and treatment selection in recurrent ovarian cancer. However, the emergence of targeted agents, such as bevacizumab and poly (ADP-ribose) polymerase inhibitors, has complicated its clinical utility. In contrast, emerging evidence suggests that platinum sensitivity may also be applicable to recurrent endometrial cancer. As in ovarian cancer, a prolonged platinum-free interval (PFI) in recurrent endometrial cancer is associated with an improved efficacy of subsequent platinum-based chemotherapy. The PFI is linearly correlated with the response rate to platinum re-administration, progression-free survival, and overall survival. Patients are typically classified as having platinum-resistant or platinum-sensitive disease based on a PFI cutoff of 6 or 12 months. However, unlike in ovarian cancer—where the duration of response to second-line platinum-based chemotherapy rarely exceeds the prior PFI (~3%)—approximately 30% of patients with recurrent endometrial cancer exhibit a sustained response to platinum rechallenge that extends beyond their preceding PFI. Despite the incorporation of immune checkpoint inhibitors into the treatment landscape of endometrial cancer, the role of platinum sensitivity in clinical decision-making—particularly regarding treatment sequencing and drug selection—remains a critical and unresolved issue. Further research is warranted to elucidate the mechanisms underlying platinum resistance and to guide optimal therapeutic strategies. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 26 9 2025 The Possibility of Plasma Membrane Transporters as Drug Targets in Oral Cancers 4310 EN Chiharu Sogawa Department of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of Technology Katsumitsu Shimada Department of Clinical Phathophysiology, Matsumoto Dental University Keisuke Nakano Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Plasma membrane transporters are increasingly recognized as potential drug targets for oral cancer, particularly oral squamous cell carcinoma (OSCC). These transporters play crucial roles in cancer cell metabolism, drug resistance, and the tumor microenvironment, making them attractive targets for therapeutic intervention. Among the two main families of plasma membrane transporters, ATP-binding cassette (ABC) transporters have long been known to be involved in drug efflux and contribute to chemoresistance in cancer cells. On the other hand, solute carriers (SLCs) are also a family of transporters that facilitate the transport of various substrates, including nutrients and drugs, and have recently been shown to contribute to cancer chemosensitivity, metabolism, and proliferation. SLC transporters have been identified as potential cancer biomarkers and therapeutic targets, and their expression profiles suggest that they could be utilized in precision oncology approaches. We summarize previous reports on the expression and role of ABC and SLC transporters in oral cancer and discuss their potential as therapeutic targets. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 0002-8177 156 2 2025 The greater palatine nerve and artery both supply the maxillary teeth 151 159.e1 EN Joe Iwanaga Division of Gross and Clinical Anatomy, Department of Anatomy, School of Medicine, Kurume University Yohei Takeshita Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Muralidharan Anbalagan Department of Structural and Cellular Biology, School of Medicine, Tulane University Binghao Zou Department of Structural and Cellular Biology, School of Medicine, Tulane University Taku Toriumi Department of Anatomy, School of Life Dentistry at Niigata, The Nippon Dental University Yuki Kunisada Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University R. Shane Tubbs University of Queensland Background. It is generally accepted that the greater palatine nerve and artery supply the palatal mucosa, gingiva, and glands, but not the bone or tooth adjacent to those tissues. When the bony palate is observed closely, multiple small foramina are seen on the palatal surface of the alveolar process. The authors hypothesized that the greater palatine nerve and artery might supply the maxillary teeth via the foramina on the palatal surface of the alveolar process and the superior alveolar nerve and artery. The authors aimed to investigate the palatal innervation and blood supply of the maxillary teeth. Methods. Eight cadaveric maxillae containing most teeth or alveolar sockets were selected. The mean age at the time of death was 82.4 years. The samples were examined with colored water injection, latex injection, microcomputed tomography with contrast dye, gross anatomic dissection, and histologic observation. Results. Through both injection studies and microcomputed tomographic analysis, the authors found that the small foramina on and around the greater palatine groove connected to the alveolar process and tooth sockets. The small foramina in the greater palatine and incisive canal also continued inside the alveolar process and the tooth sockets. Conclusions. The alveolar branches of the greater palatine nerve and artery as well as the nasopalatine nerve and sphenopalatine artery supply maxillary teeth, alveolar bone, and periodontal tissue via the palatal alveolar foramina with superior alveolar nerves and arteries. Practical Implications. This knowledge is essential for dentists when administering local anesthetic to the maxillary teeth and performing an osteotomy. Anatomic and dental textbooks should be updated with this new knowledge for better patient care. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0168-0102 219 2025 Establishment of a transgenic strain for the whole brain calcium imaging in larval medaka fish (Oryzias latipes) 104944 EN Takahide Seki Graduate School of Life Sciences, Tohoku University Kazuhiro Miyanari Graduate School of Science and Engineering, Saitama University Asuka Shiraishi Graduate School of Science and Engineering, Saitama University Sachiko Tsuda Graduate School of Science and Engineering, Saitama University Satoshi Ansai Ushimado Marine Institute, Okayama University Hideaki Takeuchi Graduate School of Life Sciences, Tohoku University GCaMP-based calcium imaging is a powerful tool for investigating neural function in specific neurons. We generated transgenic (Tg) medaka strains expressing jGCaMP7s across extensive brain regions under the control of the gap43 promoter. Using these Tg larvae, calcium imaging successfully detected a tricaine-induced suppression of spontaneous neural activity and topographical visual responses in the optic tectum elicited by moving paramecia or optical fiber stimulation. These results indicate that our Tg medaka strains provide a versatile platform for investigating neural dynamics and their responses to various stimuli. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0163-2116 2025 Berberine Prevents NSAID-Induced Small Intestinal Injury by Protecting Intestinal Barrier and Inhibiting Inflammasome-Associated Activation EN Mikako Ishiguro Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masahiro Takahara Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Akinobu Takaki Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Sakiko Hiraoka Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Jyunki Toyosawa Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuki Aoyama Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shoko Igawa Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasushi Yamasaki Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshihiro Inokuchi Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hideaki Kinugasa Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Motoyuki Otsuka Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Background Nonsteroidal anti-inflammatory drugs (NSAID), which are commonly used to manage pain and inflammation, often cause gastrointestinal injuries, including small intestinal damage. Berberine (BBR) is a traditional Chinese medicine that protects against these injuries. However, the mechanism of action is not fully understood. Aims This study aimed to evaluate the protective effects of BBR against NSAID-induced intestinal injury and elucidate the underlying molecular mechanisms. Methods We evaluated the effects of BBR on NSAID-induced intestinal injury using a combination of mouse models and human gut organoids. Mice were treated with indomethacin with or without BBR to induce small intestinal injury. Human gut organoids were exposed to NSAID, with or without BBR, to assess their direct epithelial effects. Histological analyses, cytokine measurements, and Western blotting were performed to evaluate intestinal damage, tight junction integrity, and inflammasome-associated activation. Results In NSAID-treated mice, BBR markedly reduced ulcers and adhesions and preserved ileal Claudin-1, Occludin, and Zonula Occludens-1 (ZO-1) levels. BBR inhibited both NOD-like receptor family pyrin domain-containing 6 and NOD-like receptor family caspase recruitment domain–containing protein 4 inflammasome activation, reducing Caspase-1 maturation and downstream interleukin-1β and tumor necrosis factor-α release. In human gut organoids, BBR demonstrated comparable protective effects by directly mitigating NSAID-induced epithelial barrier disruption caused by Claudin-1 and Occludin downregulation, although it did not restore ZO-1 expression. Conclusions BBR effectively prevented NSAID-induced small intestinal injury by maintaining tight junction integrity and inhibiting inflammasome-associated activation, indicating its potential as a therapeutic agent against such damage. No potential conflict of interest relevant to this article was reported.

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

Korean Association for the Study of Intestinal Diseases Acta Medica Okayama 1598-9100 2025 The duration of prior anti-tumor necrosis factor agents is associated with the effectiveness of vedolizumab in patients with ulcerative colitis: a real-world multicenter retrospective study EN Taku Kobayashi Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital Tadakazu Hisamatsu Department of Gastroenterology and Hepatology, Kyorin University School of Medicine Satoshi Motoya Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital Minoru Matsuura Department of Gastroenterology and Hepatology, Kyorin University School of Medicine Toshimitsu Fujii Department of Gastroenterology and Hepatology, Institute of Science Tokyo Reiko Kunisaki Inflammatory Bowel Disease Center, Yokohama City University Medical Center Tomoyoshi Shibuya Department of Gastroenterology, Juntendo University School of Medicine Ken Takeuchi Department of Gastroenterology and Hepatology, IBD Center, Tsujinaka Hospital Kashiwanoha Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Hospital Hiroshi Yasuda Department of Gastroenterology, St. Marianna University School of Medicine Kaoru Yokoyama Department of Gastroenterology, Kitasato University School of Medicine Noritaka Takatsu Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital Atsuo Maemoto Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital Toshiyuki Tahara Department of Gastroenterology, Saiseikai Utsunomiya Hospital Keiichi Tominaga Department of Gastroenterology, Dokkyo Medical University Masaaki Shimada Department of Gastroenterology, NHO Nagoya Medical Center Nobuaki Kuno Department of Gastroenterology and Medicine, Fukuoka University Hospital Mary Cavaliere Japan Medical Office, Takeda Pharmaceutical Company Limited Kaori Ishiguro Japan Medical Office, Takeda Pharmaceutical Company Limited Jovelle L Fernandez Japan Medical Office, Takeda Pharmaceutical Company Limited Toshifumi Hibi Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital Background/Aims Previous literature suggests that the response of patients with ulcerative colitis to vedolizumab may be affected by previous biologic therapy exposure. This real-world study evaluated vedolizumab treatment effectiveness in biologicnon-naïve patients. Methods This was a multicenter, retrospective, observational chart review of records from 16 hospitals in Japan (December 1, 2018, to February 29, 2020). Included patients who had ulcerative colitis, were aged ≥ 20 years, and received at least 1 dose of vedolizumab. Outcomes included clinical remission rates from weeks 2 to 54 according to prior biologic exposure status and factors associated with clinical remission up to week 54. Results A total of 370 eligible patients were included. Clinical remission rates were significantly higher in biologic-naïve (n=197) than in biologic-non-naïve (n=173) patients for weeks 2 to 54 of vedolizumab treatment. Higher clinical remission rates up to week 54 were significantly associated with lower disease severity (partial Mayo score ≤ 4, P= 0.001; albumin ≥ 3.0, P= 0.019) and the duration of prior anti-tumor necrosis factor α (anti-TNFα) therapy (P= 0.026). Patients with anti-TNFα therapy durations of < 3 months, 3 to < 12 months, and ≥ 12 months had clinical remission rates of 28.1%, 32.7%, and 60.0%, respectively (P= 0.001 across groups). Conclusions The effectiveness of vedolizumab in biologic-non-naïve patients was significantly influenced by duration of prior anti-TNFα therapy. (Japanese Registry of Clinical Trials: jRCT-1080225363) No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0815-9319 40 6 2025 Real-World Effectiveness and Safety of Vedolizumab in Patients ≥ 70 Versus < 70 Years With Ulcerative Colitis: Multicenter Retrospective Study 1435 1445 EN Tadakazu Hisamatsu Department of Gastroenterology and Hepatology, Kyorin University School of Medicine Taku Kobayashi Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital Satoshi Motoya Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital Toshimitsu Fujii Department of Gastroenterology and Hepatology, Institute of Science Tokyo Reiko Kunisaki Inflammatory Bowel Disease Center, Yokohama City University Medical Center Tomoyoshi Shibuya Department of Gastroenterology, Juntendo University School of Medicine Minoru Matsuura Department of Gastroenterology and Hepatology, Kyorin University School of Medicine Sakiko Hiraoka Ken Takeuchi Department of Gastroenterology and Hepatology, IBD Center, Tsujinaka Hospital Kashiwanoha Hiroshi Yasuda Department of Gastroenterology, St. Marianna University School of Medicine Kaoru Yokoyama Department of Gastroenterology, Kitasato University School of Medicine Noritaka Takatsu Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital Atsuo Maemoto Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital Toshiyuki Tahara Department of Gastroenterology, Saiseikai Utsunomiya Hospital Keiichi Tominaga Department of Gastroenterology, Dokkyo Medical University Masaaki Shimada Department of Gastroenterology, NHO Nagoya Medical Center Nobuaki Kuno Department of Gastroenterology and Medicine, Fukuoka University Hospital Jovelle L. Fernandez Japan Medical Office, Takeda Pharmaceutical Company Limited Lisa Hirose Japan Medical Office, Takeda Pharmaceutical Company Limited Kaori Ishiguro Japan Medical Office, Takeda Pharmaceutical Company Limited Mary Cavaliere Japan Medical Office, Takeda Pharmaceutical Company Limited Toshifumi Hibi Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital Background and Aim: Vedolizumab (VDZ) is often used in older patients with ulcerative colitis (UC) in clinical practice; however, real-world evidence is still limited, including in those with late-onset UC. Methods: This post hoc analysis of a multicenter, retrospective, observational chart review, enrolling 370 patients with UC receiving VDZ between December 2018 and February 2020, compared effectiveness and safety of VDZ among patients ≥ 70 (n = 40) versus < 70 years (n = 330), and among patients ≥ 70 years with and without late-onset UC (age at disease onset: ≥ 70 [n = 13] versus < 70 years [n = 26]). Results: There were no differences between patients ≥ 70 and < 70 years in clinical remission rates (week 6: 57.5% vs. 47.6%, p = 0.9174; week 14: 62.5% vs. 54.8%, p = 0.1317; week 54: 47.5% vs. 46.4%, p = 0.8149), primary nonresponse (10.0% vs. 15.5%, p = 0.6248), loss of response (12.5% vs. 9.4%, p = 0.5675), or overall safety. Among patients ≥ 70 years, the incidence of adverse drug reactions was numerically greater in those with concomitant corticosteroids than in those without. For older patients with and without late-onset UC, week 54 remission rates were 23.1% versus 57.7% (p = 0.0544); surgery was reported in 3/13 versus 2/26 patients and hospitalization in 5/13 versus 6/26 patients. One death was reported in patients with late-onset UC. Conclusions: VDZ effectiveness and safety were similar in patients ≥ 70 and < 70 years; VDZ may be a suitable treatment option for patients ≥ 70 years with UC. Patients with late-onset UC tended to have more frequent surgery/hospitalization and lower effectiveness than those without, possibly necessitating greater caution when using VDZ. Trial Registration: Japanese Registry of Clinical Trials registration number: jRCT-1080225363 No potential conflict of interest relevant to this article was reported.

Korean Association for the Study of Intestinal Diseases Acta Medica Okayama 1598-9100 2025 Factors affecting 1-year persistence with vedolizumab for ulcerative colitis: a multicenter, retrospective real-world study EN Taku Kobayashi Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital Tadakazu Hisamatsu Department of Gastroenterology and Hepatology, Kyorin University School of Medicine Satoshi Motoya Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital Toshimitsu Fujii Department of Gastroenterology and Hepatology, Institute of Science Tokyo Reiko Kunisaki Inflammatory Bowel Disease Center, Yokohama City University Medical Center Tomoyoshi Shibuya Department of Gastroenterology, Juntendo University School of Medicine Minoru Matsuura Department of Gastroenterology and Hepatology, Kyorin University School of Medicine Ken Takeuchi Department of Gastroenterology and Hepatology, IBD Center Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Hospital Hiroshi Yasuda Department of Gastroenterology, St. Marianna University School of Medicine Kaoru Yokoyama Department of Gastroenterology, Kitasato University School of Medicine Noritaka Takatsu Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital Atsuo Maemoto Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital Toshiyuki Tahara Department of Gastroenterology, Saiseikai Utsunomiya Hospital Keiichi Tominaga Department of Gastroenterology, Dokkyo Medical University Masaaki Shimada Department of Gastroenterology, NHO Nagoya Medical Center Nobuaki Kuno Department of Gastroenterology and Medicine, Fukuoka University Hospital Jovelle L. Fernandez Japan Medical Office, Takeda Pharmaceutical Company Limited Kaori Ishiguro Japan Medical Office, Takeda Pharmaceutical Company Limited Mary Cavaliere Japan Medical Office, Takeda Pharmaceutical Company Limited Hisato Deguchi Japan Medical Office, Takeda Pharmaceutical Company Limited Toshifumi Hibi Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital Background/Aims The objectives of this real-world study were to determine 1-year persistence with vedolizumab in patients with ulcerative colitis and to evaluate factors contributing to loss of response. Methods In this multicenter, retrospective, observational chart review, patients with moderately to severely active ulcerative colitis who received ≥ 1 dose of vedolizumab in clinical practice at 16 tertiary hospitals in Japan (from December 2018 through February 2020) were enrolled. Results Persistence with vedolizumab was 64.5% (n = 370); the median follow-up time was 53.2 weeks. Discontinuation due to loss of response among initial clinical remitters was reported in 12.5% (35/281) of patients. Multivariate analysis showed that concomitant use of tacrolimus (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.00–7.62; P= 0.050) and shorter disease duration (OR for median duration ≥ 7.8 years vs. < 7.8 years, 0.33; 95% CI, 0.13–0.82; P= 0.017) were associated with discontinuation due to loss of response. Loss of response was not associated with prior use of anti-tumor necrosis factor alpha therapy, age at the time of treatment, disease severity, or concomitant corticosteroids or immunomodulators. Of the 25 patients with disease duration < 1 year, 32.0% discontinued due to loss of response. Conclusions Persistence with vedolizumab was consistent with previous reports. Use of tacrolimus and shorter disease duration were the main predictors of decreased persistence. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 Mimicking Contralateral Pneumothorax during Thoracoscopic Bullectomy Associated with Intraoperative Hyperinflation of a Large Bulla in an Obese Patient 311 315 EN Kei Matsubara Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Kei Matsubara Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Yutaka Hirano Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Toshiya Fujiwara Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Case Report 10.18926/AMO/69159 A 55-year-old obese Japanese male with left pneumothorax presented to our hospital. Bilateral pulmonary emphysema was confirmed. Persistent air leakage was observed, and a thoracoscopic bullectomy was performed. Although the thoracoscopic bullectomy was completed uneventfully, pre-extubation chest X-ray imaging indicated hyper-lucency occupying the right upper part of the thoracic cavity, suggesting right-sided pneumothorax. CT imaging indicated a right-upper-lobe expanded bulla. Extubation was performed, and the hyperinflated bulla gradually deflated. Careful management of bulla expansion and respiratory status may be necessary for patients with obesity and large bullae, especially in one-lung ventilation cases. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 Femoral and Global Femoral Offset, but not Anteroposterior Offset, to Improve Postoperative Outcomes Following Total Hip Arthroplasty: Considerations Independent of the Contralateral Side 269 278 EN Norio Imai Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences Yuki Hirano Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Daisuke Homma Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Yuki Endo Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Yoji Horigome Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences Hayato Suzuki Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Hiroyuki Kawashima Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Original Article 10.18926/AMO/69152 The global femoral offset (the sum of the acetabular and femoral offsets) influences outcomes after total hip arthroplasty (THA). The optimal offset using plain radiographs has been reported, but internal and external rotations of the hip affect the offset value, producing unclear results when the nonsurgical side is not intact. We investigated the relationship between a functional hip score, i.e., the Harris Hip Score (HHS) and its effect on the post-THA anteroposterior and lateral offsets, and we sought to identify the optimal offset value. The cases of 158 patients with hemilateral hip osteoarthritis who underwent THA at a single center were retrospectively analyzed in this cross-sectional study. Three-dimensional pelvic and femoral models generated from computed tomography were used to examine several parameters, and the results revealed a significant binomial correlation among the modified HHS and femoral and global femoral offsets, with maximum values of 21.3 mm and 40 mm/100 cm body height, respectively. Pelvic and femoral parameters were measured and evaluated via alignment with a specific coordinate system. Our findings indicate that preoperative planning using these parameters may improve postoperative hip function, even when the nonoperative side is unsuitable for use as a reference, as in bilateral hip osteoarthritis cases. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 Outcome of Decompression Surgery Following Rapid Neurological Deterioration in Patients with Spinal Cord Injury Without Radiographic Evidence of Trauma (SCIWORET) 261 267 EN Yuichi Hirata Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiaki Sugahara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Sasada Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hayato Miyake Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Nagase Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takao Yasuhara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/69151 Cervical spondylotic myelopathy (CSM) and ossification of the posterior longitudinal ligament (OPLL) increase the likelihood of spinal cord injury without radiographic evidence of trauma (SCIWORET). Opinions regarding the optimal timing for surgery in such cases vary, however. We retrospectively investigated the demographics and outcomes of patients with SCIWORET who underwent surgery shortly after experiencing rapid neurological deterioration, and we matched patients who underwent standby surgery for CSM or OPLL. Although the optimal timing of surgery for SCIWORET remains unclear, our findings suggest that early stage surgery for SCIWORET may yield favorable neurological improvements. 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. 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. 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.

Elsevier BV Acta Medica Okayama 0304-3800 508 2025 Enhanced aboveground biomass density estimation in Central Vietnamese forests 111242 EN Viet Hoang Ho Graduate School of Environmental and Life Science, Okayama University Hidenori Morita Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Felix Bachofer German Aerospace Center (DLR), Earth Observation Center Thanh Ha Ho University of Agriculture and Forestry, Hue University Accurate estimation of spatially explicit forest aboveground biomass density (AGBD) is essential for supporting climate change mitigation strategies. Recent studies have demonstrated the predictive effectiveness of the random forest (RF) algorithm in forest AGBD estimation utilizing multi-source remote sensing (RS) data. However, the RF-based estimates may be further enhanced by integrating RF with kriging techniques that account for spatial autocorrelation in model residuals. Therefore, we investigated the performance of random forest ordinary kriging (RFOK) and random forest co-kriging (RFCK) for estimating AGBD in Central Vietnamese forests using Advanced Land Observing Satellite-2 Phased Array L-band Synthetic Aperture Radar-2 (ALOS-2 PALSAR-2), Sentinel-1 (S1), and Sentinel-2 (S2) imageries. 277 predictors, including spectral bands, radar backscatter coefficients, vegetation indices, biophysical variables, and texture metrics, were derived from these RS datasets and statistically linked to field measurements from 104 geo-referenced forest inventory plots. The results showed that textures, modified chlorophyll absorption ratio index (MCARI), and radar backscatters were key contributors to AGBD variability. The fusion of ALOS-2 PALSAR-2 and S2 data yielded the highest RF performance, with coefficient of determination (R2), root mean square error (RMSE), and mean absolute error (MAE) achieving 0.75, 39.15 t.ha-1, and 32.20 t.ha-1, respectively. Incorporating interpolated residuals by ordinary kriging and co-kriging into RF predictions enhanced estimation accuracy, with relative improvements of 5.74–7.04 % in R2, 8.73–10.91 % in RMSE, and 13.62–15.27 % in MAE, yet these gains remained limited. Although RFOK achieved marginally better accuracy (R2 = 0.80, RMSE = 34.88 t.ha-1, MAE = 27.28 t.ha-1) compared to RFCK (R2 = 0.79, RMSE = 35.73 t.ha-1, MAE = 27.81 t.ha-1), the latter reduced estimation bias more effectively, likely due to the inclusion of elevation as a covariate in the co-kriging process. These findings underscore the potential of the hybrid RF-kriging frameworks for improving spatial AGBD estimation, offering a robust approach for carbon accounting in tropical ecosystems. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1439-0108 25 5 2025 Comparison of geostatistics, machine learning algorithms, and their hybrid approaches for modeling soil organic carbon density in tropical forests 1554 1577 EN Viet Hoang Ho Graduate School of Environmental and Life Science, Okayama University Hidenori Morita Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Thanh Ha Ho University of Agriculture and Forestry, Hue University Felix Bachofer German Aerospace Center (DLR), Earth Observation Center Thi Thuong Nguyen University of Agriculture and Forestry, Hue University Purpose Understanding the spatial variability of soil organic carbon density (SOCD) in tropical forests is necessary for efficient climate change mitigation initiatives. However, accurately modeling SOCD in these landscapes is challenging due to low-density sampling efforts and the limited availability of in-situ data caused by constrained accessibility. In this study, we aimed to explore the most suitable modeling technique for SOCD estimation in the context of tropical forest ecosystems. Methods To support the research, thirty predictor covariates derived from remote sensing data, topographic attributes, climatic factors, and geographic positions were utilized, along with 104 soil samples collected from the top 30 cm of soil in Central Vietnamese tropical forests. We compared the effectiveness of geostatistics (ordinary kriging, universal kriging, and kriging with external drift), machine learning (ML) algorithms (random forest and boosted regression tree), and their hybrid approaches (random forest regression kriging and boosted regression tree regression kriging) for the prediction of SOCD. Prediction accuracy was evaluated using the coefficient of determination (R2), the root mean squared error (RMSE), and the mean absolute error (MAE) obtained from leave-one-out cross-validation. Results The study results indicated that hybrid approaches performed best in predicting forest SOCD with the greatest values of R2 and the lowest values of MAE and RMSE, and the ML algorithms were more accurate than geostatistics. Additionally, the prediction maps produced by the hybridization showed the most realistic SOCD pattern, whereas the kriged maps were prone to have smoother patterns, and ML-based maps were inclined to possess more detailed patterns. The result also revealed the superiority of the ML plus residual kriging approaches over the ML models in reducing the underestimation of large SOCD values in high-altitude mountain areas and the overestimation of low SOCD values in low-lying terrain areas. Conclusion Our findings suggest that the hybrid approaches of geostatistics and ML models are most suitable for modeling SOCD in tropical forests. No potential conflict of interest relevant to this article was reported.

Spandidos Publications Acta Medica Okayama 2049-9450 23 3 2025 Association of the expression of 5‑FU biomarkers with aging and prognosis in elderly patients with lung cancer treated with S‑1 adjuvant chemotherapy: Follow‑up results of the Setouchi Lung Cancer Group Study 1201 79 EN Junichi Soh Department of Thoracic Surgery, Okayama University Hospital Hiromasa Yamamoto Department of Thoracic Surgery, Okayama University Hospital Norihito Okumura Department of Thoracic Surgery, Kurashiki Central Hospital Hiroyuki Suzuki Department of Chest Surgery, Fukushima Medical University Hospital Masao Nakata Department of General Thoracic Surgery, Kawasaki Medical School Hospital Toshiya Fujiwara Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Kenicehi Gemba Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Hiroshima 720‑0001, Japan; 8Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital Isao Sano Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital Takuji Fujinaga Department of General Thoracic Surgery, National Hospital Organization Nagara Medical Center Masafumi Kataoka Department of Surgery and Respiratory Center, Okayama Saiseikai General Hospital Yasuhiro Terasaki Department of Respiratory Surgery, Saga Medical Center Koseikan Nobukazu Fujimoto Department of Medical Oncology and Respiratory Medicine, Okayama Rosai Hospital Kazuhiko Kataoka Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center Shinji Kosaka Department of Thoracic Surgery, Shimane Prefectural Central Hospital Motohiro Yamashita Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center Hidetoshi Inokawa Department of Thoracic Surgery, National Hospital Organization Yamaguchi‑Ube Medical Center Masaaki Inoue Department of Thoracic Surgery, Shimonoseki City Hospital Hiroshige Nakamura Division of General Thoracic Surgery, Tottori University Hospital Yoshinori Yamashita Department of Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center Yuta Takahashi Department of Thoracic Surgery, Okayama University Hospital Hidejiro Torigoe Department of Thoracic Surgery, Okayama University Hospital Hiroki Sato Department of Thoracic Surgery, Okayama University Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Hospital Satoshi Morita Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine Keitaro Matsuo Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute Junichi Sakamoto Tokai Central Hospital Hiroshi Date Department of Thoracic Surgery, Kyoto University Hospital Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Managing elderly patients presents several challenges because of age‑related declines; however, age should not be the sole determinant for adjuvant treatment decisions in patients with non‑small cell lung cancer (NSCLC). Moreover, age may affect the expression of 5‑fluorouracil (5‑FU) biomarkers. The present study assessed: i) The effect of age on the expression levels of 5‑FU biomarkers by analyzing a public database; and ii) the ability of these biomarkers to predict clinical outcomes in elderly patients with NSCLC who underwent complete resection in the Setouchi Lung Cancer Group Study 1201 (SCLG1201) followed by S‑1 adjuvant chemotherapy. Changes in gene expression levels across age groups were assessed by analyzing The Cancer Genome Atlas (TCGA) database. The expression of 5‑FU biomarkers, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase, epidermal growth factor receptor (EGFR) and excision repair cross‑complementation group 1 (ERCC1), were assessed via quantitative reverse‑transcription PCR assays in 89 elderly patients (≥75 years) with NSCLC who received adjuvant chemotherapy with oral fluoropyrimidine prodrug S‑1 in the SLCG1201 trial. TCGA database analysis (n=955) showed that TS expression decreased significantly with aging, especially in the age group ≥75. In the SCLG1201 trial, univariate analysis revealed that EGFR upregulation and TS downregulation were correlated with favorable recurrence‑free survival (RFS) and overall survival (OS), respectively. Multivariate analysis demonstrated that pathological stage was an independent prognostic factor for both RFS and OS. EGFR mutations were associated with upregulation of DPD and EGFR, and downregulation of TS and ERCC1. In conclusion, although pathological stage is an independent prognostic factor for survival, EGFR upregulation and TS downregulation may be a greater predictor of clinical outcomes in elderly patients with NSCLC treated with S‑1 adjuvant chemotherapy. The age‑related decrease in TS expression supports the potential benefit of 5‑FU therapies in elderly patients. Nonetheless, further research is warranted to validate these results. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1550-4131 37 2 2025 Maternal circadian rhythms during pregnancy dictate metabolic plasticity in offspring 395 412.e6 EN Na Yao Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Kenichiro Kinouchi Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Manami Katoh Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo Kousha Changizi Ashtiani Department of Computer Science, University of California Sherif Abdelkarim Department of Computer Science, University of California Hiroyuki Morimoto Department of Integrative Anatomy, Nagoya City University Graduate School of Medical Sciences Takuto Torimitsu Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Takahide Kozuma Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Akihide Iwahara Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Shotaro Kosugi Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Jin Komuro Department of Cardiology, Keio University School of Medicine Kyosuke Kato Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Shun Tonomura Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Toshifumi Nakamura Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Arata Itoh Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Shintaro Yamaguchi Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Jun Yoshino Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Junichiro Irie Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Hisayuki Hashimoto Department of Cardiology, Keio University School of Medicine Shinsuke Yuasa Department of Cardiovascular Medicine, Academic Field, Dentistry and Pharmaceutical Sciences, Okayama University Akiko Satoh Department of Integrative Physiology, Institute of Development, Aging and Cancer, Tohoku University Yohei Mikami Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine Shusaku Uchida Department of Integrative Anatomy, Nagoya City University Graduate School of Medical Sciences Takatoshi Ueki Department of Integrative Anatomy, Nagoya City University Graduate School of Medical Sciences Seitaro Nomura Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo Pierre Baldi Department of Computer Science, University of California Kaori Hayashi Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Hiroshi Itoh Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine Tissue-level oscillation is achieved by tissue-intrinsic clocks along with network-dependent signals originating from distal organs and organismal behavior. Yet, it remains unexplored whether maternal circadian rhythms during pregnancy influence fetal rhythms and impact long-term susceptibility to dietary challenges in offspring. Here, we demonstrate that circadian disruption during pregnancy decreased placental and neonatal weight yet retained transcriptional and structural maturation. Intriguingly, diet-induced obesity was exacerbated in parallel with arrhythmic feeding behavior, hypothalamic leptin resistance, and hepatic circadian reprogramming in offspring of chronodisrupted mothers. In utero circadian desynchrony altered the phase-relationship between the mother and fetus and impacted placental efficiency. Temporal feeding restriction in offspring failed to fully prevent obesity, whereas the circadian alignment of caloric restriction with the onset of the active phase virtually ameliorated the phenotype. Thus, maternal circadian rhythms during pregnancy confer adaptive properties to metabolic functions in offspring and provide insights into the developmental origins of health and disease. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0028-0836 637 8046 2025 Centrophilic retrotransposon integration via CENH3 chromatin in Arabidopsis 744 748 EN Sayuri Tsukahara Department of Biological Sciences, The University of Tokyo Alexandros Bousios School of Life Sciences, University of Sussex Estela Perez-Roman School of Life Sciences, University of Sussex Sota Yamaguchi Department of Biological Sciences, The University of Tokyo Basile Leduque Institute of Plant Sciences Paris‐Saclay (IPS2), Centre National de la Recherche Scientifique, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement, Université Evry, Université Paris Aimi Nakano Department of Biological Sciences, The University of Tokyo Matthew Naish Department of Plant Sciences, University of Cambridge Akihisa Osakabe Department of Biological Sciences, The University of Tokyo Atsushi Toyoda Center for Genetic Resource Information, National Institute of Genetics Hidetaka Ito Faculty of Science, Hokkaido University Alejandro Edera Institute of Plant Sciences Paris‐Saclay (IPS2), Centre National de la Recherche Scientifique, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement, Université Evry, Université Paris Sayaka Tominaga Department of Biological Sciences, The University of Tokyo Juliarni Department of Biological Sciences, The University of Tokyo Kae Kato Department of Integrated Genetics, National Institute of Genetics Shoko Oda Department of Biological Sciences, The University of Tokyo Soichi Inagaki Department of Biological Sciences, The University of Tokyo Zdravko Lorković Gregor Mendel Institute (GMI), Austrian Academy of Sciences, Vienna BioCenter (VBC) Kiyotaka Nagaki Institute of Plant Science and Resources, Okayama University Frédéric Berger Gregor Mendel Institute (GMI), Austrian Academy of Sciences, Vienna BioCenter (VBC) Akira Kawabe Faculty of Life Sciences, Kyoto Sangyo University Leandro Quadrana Institute of Plant Sciences Paris‐Saclay (IPS2), Centre National de la Recherche Scientifique, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement, Université Evry, Université Paris Ian Henderson Department of Plant Sciences, University of Cambridge Tetsuji Kakutani Department of Biological Sciences, The University of Tokyo In organisms ranging from vertebrates to plants, major components of centromeres are rapidly evolving repeat sequences, such as tandem repeats (TRs) and transposable elements (TEs), which harbour centromere-specific histone H3 (CENH3)1,2. Complete centromere structures recently determined in human and Arabidopsis suggest frequent integration and purging of retrotransposons within the TR regions of centromeres3,4,5. Despite the high impact of ‘centrophilic’ retrotransposons on the paradox of rapid centromere evolution, the mechanisms involved in centromere targeting remain poorly understood in any organism. Here we show that both Ty3 and Ty1 long terminal repeat retrotransposons rapidly turnover within the centromeric TRs of Arabidopsis species. We demonstrate that the Ty1/Copia element Tal1 (Transposon of Arabidopsis lyrata 1) integrates de novo into regions occupied by CENH3 in Arabidopsis thaliana, and that ectopic expansion of the CENH3 region results in spread of Tal1 integration regions. The integration spectra of chimeric TEs reveal the key structural variations responsible for contrasting chromatin-targeting specificities to centromeres versus gene-rich regions, which have recurrently converted during the evolution of these TEs. Our findings show the impact of centromeric chromatin on TE-mediated rapid centromere evolution, with relevance across eukaryotic genomes. No potential conflict of interest relevant to this article was reported.

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

Royal Society of Chemistry (RSC) Acta Medica Okayama 2041-6520 16 26 2025 Collective motions in the primary coordination sphere: a critical functional framework for catalytic activity of the oxygen-evolving complex of photosystem II 12024 EN Hiroshi Isobe Takayoshi Suzuki Research Institute for Interdisciplinary Science, Okayama University Michihiro Suga Research Institute for Interdisciplinary Science, Okayama University Jian-Ren Shen Research Institute for Interdisciplinary Science, Okayama University Kizashi Yamaguchi Center for Quantum Information and Quantum Biology, Osaka University Photosynthetic water oxidation, vital for dioxygen production and light energy conversion, is catalyzed by the oxygen-evolving complex of photosystem II, where the inorganic Mn4CaO5 cluster acts as the catalytic core. In this study, we investigate the functional significance of collective motions of amino acid side chains within the primary coordination sphere of the Mn cluster, focusing on their role in modulating the energetic demands for catalytic transformations in the S3 state. We applied regularized canonical correlation analysis to quantitatively correlate the three-dimensional arrangement of coordinating atoms with catalytic driving forces computed via density functional theory. Our analysis reveals that distinct collective side chain motions profoundly influence the energetic requirements for structural reconfigurations of the Mn cluster, achieved through expansion and contraction of the ligand cavity while fine-tuning its geometry to stabilize key intermediates. Complementary predictions from a neural network-based machine learning model indicate that the coordination sphere exerts a variable energetic impact on the catalytic transformations of the Mn cluster, depending on the S-state environment. Integrated computational analyses suggest that the extended lifetime of the S3YZ˙ state, consistently observed after three flash illuminations, may result from slow, progressive protein dynamics that continuously reshape the energy landscape, thereby shifting the equilibrium positions of rapid, reversible chemical processes over time. Overall, our findings demonstrate that collective motions in the primary coordination sphere constitute an active, dynamic framework essential for the efficient execution of multi-electron catalysis under ambient conditions, while simultaneously achieving a high selectivity with irreversible nature required for effective 3O2 evolution. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2079-7737 14 5 2025 Mutagenesis Targeting the S153 Residue Within the Transmembrane β-Hairpin of Mosquito-Larvicidal Mpp46Ab Affects Its Toxicity and the Synergistic Toxicity with Cry4Aa 489 EN Tohru Hayakawa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Syun Yamaoka Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mami Asakura Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Minako Hirano Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toru Ide Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University We constructed a library of Mpp46Ab mutants, in which S153 within the transmembrane β-hairpin was randomly replaced by other amino acids. Mutagenesis and subsequent primary screening yielded 10 different Mpp46Ab mutants in addition to the wild type. Remarkably, S153 was replaced with a more hydrophobic amino acid in most of the mutants, and the S153I mutant in particular exhibited significantly increased toxicity. Electrophysiologic analysis using artificial lipid bilayers revealed that the single-channel conductance and PK/PCl permeability ratio were significantly increased for S153I pores. This suggests that the formation of highly ion-permeable and highly cation-selective toxin pores increases the influx of cations and water into cells, thereby facilitating osmotic shock. In addition, the S153F, S153L, and S153I mutants exhibited significantly reduced synergistic toxicity with Cry4Aa. Electrophysiologic analysis showed that the S153F, S153L, and S153I mutants form toxin pores with a significantly reduced PK/PNa permeability ratio and a significantly increased PK/PCa permeability ratio compared to wild-type pores. Thus, our results suggest that pore formation is central to the insecticidal activity of Mpp46Ab and that the ion permeability of toxin pores is a potential indicator correlated with both toxicity and synergistic toxicity with other toxins. No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 0015-749X 71 3 2025 Physiological and Biochemical Traits of Dormancy Release and Growth Resumption in Japanese Cedar in the Warm-Temperate Zone 321 343 EN Shoma Hiejima The United Graduate School of Agricultural Sciences, Kagoshima University Hiroto Seino Graduate School of Agriculture, Forestry and Fisheries, Kagoshima University Rico Hachisuka The United Graduate School of Agricultural Sciences, Kagoshima University Yuka Watanabe Graduate School of Agriculture, Forestry and Fisheries, Kagoshima University Takakazu Matsuura Institute of Plant Science and Resources, Okayama University Izumi C. Mori Institute of Plant Science and Resources, Okayama University Shin Ugawa The United Graduate School of Agricultural Sciences, Kagoshima University Global warming will disturb dormancy release and growth resumption of trees. To better understand this process, it is important to investigate physiological and biochemical traits related to these stages. We examined dormancy release and growth resumption in Japanese cedar (Cryptomeria japonica [L.] D. Don), an evergreen needle-leaved tree, in the warm-temperate zone by evaluating budbreak under growth-promoting conditions, and simultaneously examining respiration rates and contents of carbohydrates and phytohormones in shoots from November 2022 to March 2023. A long time to budbreak and the lowest budbreak rates of 75% in November indicated shallow dormancy. Budbreak rates of 98%, short time to budbreak, and first appearance of budbreak in the field in March indicated growth resumption. Continuous changes in budbreak rates and time to budbreak between dormancy and growth resumption indicated dormancy was gradually released. Surges in budbreak rates in December indicated dormancy was almost completely released by early winter. Contents of abscisic acid (ABA) and salicylic acid (SA) decreased from November, remained low in March, and were strongly associated with budbreak rates according to principal component analysis. It was suggested that the depletion of SA led to the depletion of ABA, contributing to dormancy release and growth resumption. Fructose and trans-zeatin accumulated until February, and low levels of starch, indole-3-acetic acid, jasmonic acid, and jasmonic acid-isoleucine during winter was followed by accumulation in March. Although these biochemical traits were less related to budbreak rates compared to ABA and SA, they seemed to assist either dormancy release or growth resumption. No potential conflict of interest relevant to this article was reported.

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

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

Acta Medica Okayama 2025 侵襲性歯周炎患者から分離した血液由来細胞外小胞のプロテオーム解析 EN Kanako KODAMA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Improved linear epitope-specific autoantibody discovery and quantitative assay system EN Mirei DATE (MASUI) Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Risk Assessment for Heavy Rainfall-Induced Geohazards using Surrogate Models EN SHIYING ZHENG Graduate School of Environmental and Life Science, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Tuning the 3D Structure of Graphene Oxide Assembly for Precisely Controlled Adsorption Properties EN ISRAEL ORTIZ ANAYA Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Deeper Mechanistic Understanding of Some Reaction Processes in Electroorganic Synthesis EN Yuta NIKI Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Development of on-site environmental analytical methods for nitrogen compounds using microfluidic paper-based analytical devices EN Mika UMEDA (ISOYAMA) Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 環境中親電子物質によるDNAメチル化制御を介したケモカイン発現誘導機構 EN Tomoki TSUCHIDA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Lower Work Engagement Is Associated with Insomnia, Psychological Distress, and Neck Pain among Junior and Senior High School Teachers in Japan EN Rina TSUCHIE Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 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.

Acta Medica Okayama 2025 Inhibitory Effect of a Tankyrase Inhibitor on Mechanical Stress-Induced Protease Expression in Human Articular Chondrocytes EN Yoshifumi HOTTA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Pulmonary Flow Management by Combination Therapy of Hemostatic Clipping and Balloon Angioplasty for Right Ventricular-Pulmonary Artery Shunt in Hypoplastic Left Heart Syndrome EN Yusuke SHIGEMITSU Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Neuroprotective effect of, a flavonoid, sudachitin in mice stroke model EN OTA ELLIOTT RICARDO SATOSHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 3 2025 An Asymptomatic Perigraft Seroma in a Patient who Underwent Aortic Root Replacement for Annulo-Aortic Ectasia 205 208 EN Yasufumi Fujita Department of Cardiovascular Surgery, Kure Kyosai Hospital Shuji Shimizu Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/68728 Perigraft seroma, a sterile fluid accumulation around the graft, is a potential complication after thoracic aortic surgery. The optimal treatment strategy for a perigraft seroma with vascular compression after thoracic aortic surgery has been unclear. We describe the case of a 62-year-old Japanese male in whom an asymptomatic perigraft seroma was observed after he had undergone aortic root replacement for annulo-aortic ectasia. The seroma was successfully treated with thoracoscopic drainage and conservative therapy. Less invasive therapy, including conservative therapy, may also be an option for asymptomatic perigraft seromas observed after thoracic aortic surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 3 2025 Promising Effectiveness of Combined Chemotherapy and Immunotherapy in Patients with Advanced Non-small Cell Lung Cancer: A Real-World Prospective Observational Study (CS-Lung-003) 167 176 EN Nobuhiro Kanaji Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University Kazuya Nishii Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center Yukari Tsubata Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine Mika Nakao Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine Takae Okuno Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine Sachi Okawa Department of Allergy and Respiratory Medicine, Okayama University Hospital Kenji Takata Department of Allergy and Respiratory Medicine, Okayama University Hospital Masahiro Kodani Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University Masahiro Yamasaki Department of Respiratory Disease, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital Kazunori Fujitaka Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Tetsuya Kubota Department of Respiratory Medicine and Allergology, Kochi University Masaaki Inoue Department of Chest Surgery, Shimonoseki City Hospital Naoki Watanabe Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital CS-Lung-003 Investigator Original Article 10.18926/AMO/68724 This prospective observational study investigated the clinical status of patients with advanced non-small cell lung cancer (NSCLC) treated with cytotoxic chemotherapy+an immune checkpoint inhibitor (chemo + IO) as first-line treatment in a real-world setting. The cases of 98 patients treated with chemo + IO were prospectively collected and analyzed for effectiveness and safety. The response rate to chemo + IO was 46.9%, and the disease control rate was 76.5%. The median progression-free survival and overall survival (OS) in the total population were 5.2 and 22.3 months, respectively. The patients positive for PD-L1 (≥ 1%) showed significantly longer OS than the negative group (<1%) (median 26.7 vs. 18.7 months, p=0.04). Pre-existing interstitial lung disease (ILD) was associated with shorter OS than the absence of ILD (median 9.0 vs. 22.6 months, p<0.01). Immunerelated adverse events (irAEs) were observed in 28 patients (28.6%). The most frequent irAE was ILD (n=11); Grade 1 (n=1 patient), G2 (n=5), G3 (n=4), and only a single patient with a G5 irAE. In this CS-Lung-003 study, first-line chemo + IO in a real-world setting showed good effectiveness, comparable to that observed in international clinical trials. In real-world practice, chemo + IO is a promising and steadfast strategy. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6694 17 9 2025 Impacts of Dental Follicle Cells and Periodontal Ligament Cells on the Bone Invasion of Well-Differentiated Oral Squamous Cell Carcinoma 1559 EN Anqi Chang Department of Oral Pathology and Medicine, Okayama University Kiyofumi Takabatake Department of Oral Pathology and Medicine, Okayama University Tianyan Piao Department of Oral Pathology and Medicine, Okayama University Takuma Arashima Department of Oral Pathology and Medicine, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine, Okayama University Htoo Shwe Eain Department of Oral Pathology and Medicine, Okayama University Yamin Soe Department of Oral Pathology and Medicine, Okayama University Zin Zin Min Department of Oral Pathology and Medicine, Okayama University Keisuke Nakano Department of Oral Pathology and Medicine, Okayama University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Okayama University Background: Oral squamous cell carcinoma (OSCC) frequently invades the jawbone, leading to diagnostic and therapeutic challenges. While tumor-bone interactions have been studied, the specific roles of dental follicle cells (DFCs) and periodontal ligament cells (PDLCs) in OSCC-associated bone resorption remain unclear. This study aimed to compare the effects of DFCs and PDLCs on OSCC-induced bone invasion and elucidate the underlying mechanisms. Methods: Primary human DFCs and PDLCs were isolated from extracted third molars and characterized by Giemsa and immunofluorescence staining. An in vitro co-culture system and an in vivo xenograft mouse model were established using the HSC-2 OSCC cell line. Tumor invasion and osteoclast activation were assessed by hematoxylin and eosin (HE) and tartrate-resistant acid phosphatase (TRAP) staining. Immunohistochemical analysis was performed to evaluate the expression of receptor activator of NF-kappa B ligand (RANKL) and parathyroid hormone-related peptide (PTHrP). Results: DFCs significantly enhanced OSCC-induced bone resorption by promoting osteoclastogenesis and upregulating RANKL and PTHrP expression. In contrast, PDLCs suppressed RANKL expression and partially modulated PTHrP levels, thereby reducing osteoclast activity. Conclusions: DFCs and PDLCs exert opposite regulatory effects on OSCC-associated bone destruction. These findings underscore the importance of stromal heterogeneity and highlight the therapeutic potential of targeting specific stromal-tumor interactions to mitigate bone-invasive OSCC. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0168-0102 214 2025 The Medaka approach to evolutionary social neuroscience 32 41 EN Satoshi Ansai Ushimado Marine Institute, Okayama University Towako Hiraki-Kajiyama Graduate School of Life Sciences, Tohoku University Ryutaro Ueda Graduate School of Life Sciences, Tohoku University Takahide Seki Graduate School of Life Sciences, Tohoku University Saori Yokoi School of Pharmaceutical Sciences, Hokkaido University Takafumi Katsumura School of Medicine, Kitasato University Hideaki Takeuchi Graduate School of Life Sciences, Tohoku University Previously, the integration of comparative biological and neuroscientific approaches has led to significant advancements in social neuroscience. This review highlights the potential and future directions of evolutionary social neuroscience research utilizing medaka fishes (the family Adrianichthyidae) including Japanese medaka (Oryzias latipes). We focus on medaka social cognitive capabilities and mate choice behavior, particularly emphasizing mate preference using visual cues. Medaka fishes are also advantageous due to their abundant genetic resources, extensive genomic information, and the relative ease of laboratory breeding and genetic manipulation. Here we present some research examples of both the conventional neuroscience approach and evolutionary approach involving medaka fishes and other species. We also discuss the prospects of uncovering the molecular and cellular mechanisms underlying the diversity of visual mate preference among species. Especially, we introduce that the single-cell transcriptome technology, particularly in conjunction with 'Adaptive Circuitry Census', is an innovative tool that bridges comparative biological methods and neuroscientific approaches. Evolutionary social neuroscience research using medaka has the potential to unveil fundamental principles in neuroscience and elucidate the mechanisms responsible for generating diversity in mating strategies. 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.

Department of Mathematics, Faculty of Science, Okayama University Acta Medica Okayama 0030-1566 67 1 2025 Inseparable Gauss maps and dormant opers 1 28 EN Yasuhiro Wakabayashi Graduate School of Information Science and Technology, Osaka University The present paper aims to generalize a result by H. Kaji on Gauss maps in positive characteristic and establish an interaction with the study of dormant opers and Frobenius-projective structures. We prove a correspondence between dormant opers on a smooth projective variety and closed immersions into a projective space with purely inseparable Gauss map. By using this, we determine the subfields of the function field of a smooth curve in positive characteristic induced by Gauss maps. Moreover, this correspondence gives us a Frobenius-projective structure on a Fermat hypersurface. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 15 1 2025 A glucocorticoid-regulating molecule, Fkbp5, may interact with mitogen-activated protein kinase signaling in the organ of Corti of mice cochleae 7506 EN Asuka Sato Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryotaro Omichi Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukihide Maeda Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences FKBP5 is a 51-Da FK506-binding protein and member of the immunophilin family involved in controlling the signaling of glucocorticoid receptor from the cytosol to nucleus. Fkbp5 has previously been shown to be expressed in murine cochlear tissue, including the organ of Corti (i.e., the sensory epithelium of the cochlea). Fkbp5-/- mice as used in this study show hearing loss in the low-frequency (8-kHz) range and click-evoked auditory brainstem response (ABR) threshold compared to wild-type mice. Both Fkbp5-/- and wild-type mice showed hearing loss at all frequencies and click-ABR thresholds at 24 h and 14 days following acoustic overexposure (AO). Tissues of the organ of Corti were subjected to RNA sequencing and KEGG pathway analysis. In Fkbp5-/- mice before AO, the mitogen-activated protein kinase (MAPK) signaling pathway was dysregulated compared to wild-type mice. In wild-type mice at 12 h following AO, the most significantly modulated KEGG pathway was the TNF signaling pathway and major MAPK molecules p38 and Jun were involved in the TNF signaling pathway. In Fkbp5-/- mice at 12 h following AO, the MAPK signaling pathway was dysregulated compared to wild-type mice following AO. In conclusion, Fkbp5 interacts with MAPK signaling in the organ of Corti in mice cochleae. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 14 4 2025 Course of General Fatigue in Patients with Post-COVID-19 Conditions Who Were Prescribed Hochuekkito: A Single-Center Exploratory Pilot Study 1391 EN Kazuki Tokumasu Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nobuyoshi Matsuki Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Otsuka Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoko Sakamoto Center for Innovative Clinical Medicine, Okayama University Hospital Keigo Ueda Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yui Matsuda Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasue Sakurada Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Honda Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuhiro Nakano Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Hasegawa Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryosuke Takase Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Omura Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumio Otsuka Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: After the start of the COVID-19 pandemic, general fatigue in patients with long COVID and post-COVID-19 conditions (PCC) became a medical issue. Although there is a lack of evidence-based treatments, Kampo medicine (traditional Japanese medicine) has gained attention in Japan. At an outpatient clinic in Japan specializing in long COVID, 24% of all prescriptions were Kampo medicines, and 72% of Kampo medicine prescriptions were hochuekkito. However, there has been no prospective, quantitative study on the course of fatigue in patients with long COVID and PCC who were prescribed hochuekkito. The aim of this study was to clarify the course of fatigue in those patients. Methods: This study included patients aged 18 years or older with general fatigue who visited the long COVID specialized outpatient clinic at Okayama University Hospital and consented to participate after being prescribed hochuekkito. We reviewed the backgrounds of the patients, and we evaluated the patients' fatigue assessment scale in person or online. Results: Twenty patients were enrolled in this study from September to December in 2023. The average age of the patients was 42.9 years (SD: 15.8 years) and 12 patients (60%) were female. After hochuekkito administration, the fatigue assessment scale score decreased from 35.9 (SD: 5.9) at the initial visit to 31.2 (SD: 9.4) after 8 weeks, indicating a trend for improvement in fatigue (difference: 4.7; 95% CI: 0.5-8.9). Conclusions: A trend for improvement in fatigue was observed in patients with long COVID and PCC who were prescribed hochuekkito, indicating a potential benefit of hochuekkito for general fatigue in such patients. General fatigue in patients with long COVID or PCC can be classified as post-infectious fatigue syndrome and is considered a condition of qi deficiency in Kampo medicine, for which hochuekkito is appropriately indicated. No potential conflict of interest relevant to this article was reported.

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

American Physical Society (APS) Acta Medica Okayama 2469-9950 111 6 2025 Josephson effect and odd-frequency pairing in superconducting junctions with unconventional magnets 064502 EN Yuri Fukaya Faculty of Environmental Life, Natural Science and Technology, Okayama University Kazuki Maeda Department of Applied Physics, Nagoya University Keiji Yada Department of Applied Physics, Nagoya University Jorge Cayao Department of Physics and Astronomy, Uppsala University Yukio Tanaka Department of Applied Physics, Nagoya University Bo Lu Center for Joint Quantum Studies, Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, Department of Physics, Tianjin University We consider Josephson junctions formed by coupling two conventional superconductors via an unconventional magnet and investigate the formation of Andreev bound states, their impact on the Josephson effect, and the emergent superconducting correlations. In particular, we focus on unconventional magnets known as 𝑑-wave altermagnets and 𝑝-wave magnets. We find that the Andreev bound states in 𝑑-wave altermagnet and 𝑝𝑦-wave magnet Josephson junctions strongly depend on the transverse momentum, with a spin splitting and low-energy minima as a function of the superconducting phase difference 𝜑. In contrast, the Andreev bound states for 𝑝𝑥-wave magnets are insensitive to the transverse momentum. We then show that the Andreev bound states can be probed by the local density of states in the middle of the junction, which also reveals that 𝑑𝑥2−𝑦2- and 𝑝-wave magnet junctions are prone to host zero energy peaks. While the zero-energy peak in 𝑑𝑥2−𝑦2-wave altermagnet junctions tends to oscillate with the magnetic order, it remains robust in 𝑝-wave magnet junctions. We then discover that the Josephson current in 𝑑-wave altermagnet junctions is composed of higher harmonics of 𝜑, which originate a 𝜙-Josephson junction behavior entirely controlled by the magnetic order in 𝑑𝑥⁢𝑦-wave altermagnets. In contrast, the Josephson current in Josephson junctions with 𝑝-wave magnets exhibits a conventional sinelike profile with a fast sign change at 𝜑=𝜋 due to zero-energy Andreev bound states. We also demonstrate that the critical currents in 𝑑-wave altermagnet Josephson junctions exhibit an oscillatory decay with the increase of the magnetic order, while the oscillations are absent in 𝑝-wave magnet junctions albeit the currents exhibit a slow decay. Furthermore, we also demonstrate that the interplay of the Josephson effect and unconventional magnetic order of 𝑑-wave altermagnets and 𝑝-wave magnets originates from odd-frequency spin-triplet 𝑠-wave superconducting correlations that are otherwise absent. Our results can serve as a guide to pursue the new functionality of Josephson junctions based on unconventional magnets. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0093-691X 234 2025 Mitochondrial content and mtDNA copy number in spermatozoa and penetrability into oocytes 125 132 EN Hai Thanh Nguyen Department of Animal Science, Okayama University Son Quang Do Department of Animal Science, Okayama University Takuya Wakai Department of Animal Science, Okayama University Hiroaki Funahashi Department of Animal Science, Okayama University The current narrative review aims to summarize the relation of mitochondrial content (MC) and mitochondrial DNA copy number (MDCN) in spermatozoa with sperm penetrability, and to discuss the various determining factors during the process of spermatogenesis in mammals. There are many potential factors associated with the quantitative alteration of MC and MDCN in male gametes from spermatogenesis to ejaculation. Particularly, spermatogenesis may be the first step to jointly contribute to an incomplete reduction of MC and MDCN in spermatozoon. It appears to be now quite clear that some abnormalities during spermatogenesis and oxidative stress are the main factors highly associated with the quantitative change of MC and MDCN in spermatozoa, consequently affecting sperm quality and their penetrability into oocytes. Currently, a series of proteins contributing to form sperm midpiece during spermatogenesis and cytoplasmic elimination during spermiation have been currently identified. The present review provides insight into how these factors interact with sperm MC and MDCN, and handholds to gain a better understanding of their roles. This review also highlights the uniqueness of normal fertile spermatozoa which have relatively lower MC and MDCN, but have mitochondria that function completely in multiple pivotal physiological pathways. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0340-7004 74 3 2025 Cancer-associated fibroblasts promote pro-tumor functions of neutrophils in pancreatic cancer via IL-8: potential suppression by pirfenidone 96 EN Tomohiko Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Nogi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuki Taniguchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Yoshimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kanto Suemori Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuto Fujita Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Ohara Departments of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background The mechanisms by which neutrophils acquire pro-tumor properties remain poorly understood. In pancreatic cancer, cancer-associated fibroblasts (CAFs) may interact with neutrophils, directing them to promote tumor progression. Methods To validate the association between CAFs and neutrophils, the localization of neutrophils was examined in clinically resected pancreatic cancer specimens. CAFs were produced by culturing in cancer-conditioned media, and the effects of these CAFs on neutrophils were examined. In vitro migration and invasion assays assess the effect of CAF-activated neutrophils on cancer cells. The factors secreted by the activated neutrophils were also explored. Finally, pirfenidone (PFD) was tested to determine whether it could suppress the pro-tumor functions of activated neutrophils. Results In pancreatic cancer specimens, neutrophils tended to co-localize with IL-6-positive CAFs. Neutrophils co-cultured with CAFs increased migratory capacity and prolonged life span. CAF-affected neutrophils enhance the migratory and invasive activities of pancreatic cancer cells. IL-8 is the most upregulated cytokine secreted by the neutrophils. PFD suppresses IL-8 secretion from CAF-stimulated neutrophils and mitigates the malignant traits of pancreatic cancer cells. Conclusion CAFs activate neutrophils and enhance the malignant phenotype of pancreatic cancer. The interactions between cancer cells, CAFs, and neutrophils can be disrupted by PFD, highlighting a potential therapeutic approach. No potential conflict of interest relevant to this article was reported.

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

岡山大学農学部 Acta Medica Okayama 2186-7755 114 2025 公表学術論文等リスト　2024 27 38 EN No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0006-291X 741 2024 S-adenosylmethionine and S-adenosyl-L-homocysteine metabolism is involved in the sperm motility and in vitro fertility rate in mouse 151006 EN Tomoko Kawai Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Fujimura Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Increased fragmentation of sperm DNA has been implicated in male infertility. Folate deficiency results in impaired methionine synthesis, depletion of S-adenosylmethionine (SAM) levels, an increase in S-adenosyl-l-homocysteine (SAH) levels, and increased DNA fragmentation. Disruption of the dynamic balance between SAM and SAH may also contribute, although the details of this process are not yet fully understood. We investigated the localization of SAM, SAH, and S-adenosylhomocysteine hydrolase (SAHH), and whether SAM/SAH metabolism contributes to sperm motility and fertilization rate. SAM, SAH, and SAHH levels were assessed in the acrosome, midpiece, and tail of spermatozoa. Chemical inhibition of SAM/SAH metabolism and extracellular SAH significantly decreased the straight-line velocity (VSL), curvilinear velocity (VCL), and amplitude lateral head displacement (ALH) of sperm cells, which were thus unable to swim forward and perform oscillatory movements in place. This significantly reduced the fertilization rate. Therefore, the disruption of the SAM/SAH balance may contribute to male infertility. No potential conflict of interest relevant to this article was reported.

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

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.

BMC Acta Medica Okayama 2059-1381 10 1 2024 Case series showing the safety and changes in lipid profiles of hemodialysis patients with hypertriglyceridemia after pemafibrate administration 74 EN Rino Okada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Onishi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Naoya Kobayashi Okayama Saidaiji Hospital Hiroyuki Ishihara Okayama Saidaiji Hospital Tomohisa Yokoyama Okayama Saidaiji Hospital Tomoyo Mifune Okayama Saidaiji Hospital Yoshimasa Sakurabu Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Ichiro Nojima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morinaga Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Background Cardiovascular disease is a major cause of morbidity and mortality in patients with chronic kidney disease and end-stage renal disease (ESRD). Dyslipidemia is a key focus of cardiovascular therapy and is characterized by hypertriglyceridemia mainly caused by lipoprotein lipase-mediated metabolism of ApoC-III in patients with ESRD. Pemafbrate, a selective peroxisome proliferator-activated receptor alpha modulator, can be used regardless of renal function and inhibit ApoC-III expression in the liver. Case presentation We reported the cases of four patients on hemodialysis who met at least 175 mg/dL of triglycerides on the consecutive three tests between September 2022 and November 2022 and took 0.1 mg pemafbrate twice a day from November 2022 to May 2023. They experienced no adverse events after pemafbrate treatment. Pemafbrate signifcantly reduced triglyceride (TG) (302±72 to 140±50 mg/dL, p=0.048), total cholesterol (187±34 to 156±48 mg/dL, p=0.025), and Apo C-III (15.9±8.2 to 12.6±7.1, p=0.030) levels. Apo A-II levels signifcantly increased after treatment (27.0±6.1 to 37.1±5.8, p=0.041). Conclusions Pemafbrate decreased TG, total cholesterol, and Apo-CIII and increased Apo A-II without adverse events. Further study is needed to examine the favorable efects of pemafbrate on the risk of CVD. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1523-7060 26 51 2024 Electrogenerated Lewis Acid-Catalyzed Claisen Rearrangement of Allyl Aryl Ethers 11111 11116 EN Yuta Niki Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koichi Mitsudo Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Eisuke Sato Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Seiji Suga Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Catalysts for Claisen rearrangement have been intensively studied to overcome the need for high temperature. However, previous studies have encountered challenges, such as the need for heating, a long reaction time, and/or the need for equivalent amounts of catalyst. In this study, we introduce an effective electrogenerated boron-based Lewis acid catalyst for the aromatic Claisen rearrangement, which proceeds in a few minutes at ambient temperature. Generation of the electrogenerated Lewis acid catalyst is discussed based on NMR analysis and DFT calculations. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Establishment and Analysis of Novel In Vitro 3D Cell Culture Models of the Fibrotic Tumor Microenvironment in Pancreatic Cancer EN Hiroyoshi TANAKA Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Computer Vision-based Motion Segmentation and Its Application for Sperm Quality Estimation EN SIGIT ADINUGROHO Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Neuroprotective effects of carnosine in a mice stroke model concerning oxidative stress and inflammatory response EN XINRAN HU Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2234-2451 35 1 2023 Meniscus extrusion is a predisposing factor for determining arthroscopic treatments in partial medial meniscus posterior root tears 8 EN Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Keisuke Kintaka Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naohiro Higashihara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masanori Tamura Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Koki Kawada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Haowei Xue 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 Patients with partial medial meniscus posterior root tears (MMPRTs) sometimes require arthroscopic pullout repair because of their intolerable/repeated knee pains and continuous disturbance in gait during activities of daily living. However, the predisposing factors for future knee surgery in patients with partial MMPRTs remain unclear. We compared the findings of magnetic resonance imaging (MRI) between patients who underwent pullout repair and nonoperative management following partial MMPRTs. Methods Twenty-five patients who required arthroscopic repair for partial MMPRTs and 23 patients who were managed nonoperatively were evaluated during a mean follow-up period of 27.1 months. Sex, age, height, body weight, body mass index, duration from onset to initial MRI, MRI findings, and medial meniscus (MM) extrusion were compared between the two groups. Linear regression analysis was used to assess the correlation between MM extrusion and duration from onset to MRI examination. Results No significant differences were observed between the pullout repair and nonoperative management groups in terms of patient demographics and the positive ratio of MRI-based root tear signs. However, absolute MM extrusion in the pullout repair group (3.49 ± 0.82 mm) was larger than that in the nonoperative management group (2.48 ± 0.60 mm, P < 0.001). Extrusion of the MM (> 3 mm) was detected more frequently in the pullout repair group than in the nonoperative management group (P < 0.001). The odds ratio in the pullout repair and MM extrusion > 3 mm cases was 9.662. Linear regression analysis revealed a fair correlation between the duration from onset to MRI and MM extrusion only in the pullout repair group (0.462 mm/month increase in MM extrusion). Conclusions This study demonstrated that more severe MM extrusions were observed in the pullout repair group than in the nonoperative management group. Major extrusion (> 3 mm) was also observed more in the pullout repair group than in the nonoperative group. Assessing MM extrusion and its severity can help determine a valid treatment for patients with partial MMPRTs. Level of evidence IV, Retrospective comparative study. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0021-5155 68 6 2024 Relationships among eye dimensions in magnetic resonance images by sex, age, and strabismus type in Japanese patients with acquired strabismus and high myopia 641 650 EN Reika Kono Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ichiro Hamasaki Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Fumiko Kishimoto Division of Ophthalmology, Ibara City Hospital Takehiro Shimizu Division of Ophthalmology, Okayama City Hospital Hiroya Kindo Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kiyo Shibata Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shin Morisawa Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Purpose To investigate the relationships among eye dimensions in magnetic resonance imaging (MRI) scans by sex, age, and strabismus type in Japanese patients with acquired strabismus and high myopia. Study design Retrospective clinical case series. Methods We included 58 eyes of 29 patients with acquired strabismus and high myopia (mean age ± standard deviation: 60.2 ± 14.7 years, axial length [AL]: 28.69 ± 2.12 mm). For all eyes, the equatorial diameter of the globe/AL ratio (EAR) and the globe/orbit volume ratio (GOR) were measured using MRI. EAR and GOR values were compared between the following groups: 9 men vs. 20 women; 8 younger (< 56 years) vs. 21 older (≥ 56 years) patients; and non-esotropia strabismus (NES: 7 patients) vs. esotropia (ET: 13 patients) vs. restrictive strabismus (RS: 9 patients) groups. Results Female patients had a smaller EAR (0.87 ± 0.07) and larger GOR (0.38 ± 0.04) than male patients (0.92 ± 0.05 and 0.35 ± 0.03, both P < 0.01). Older patients had a smaller EAR (0.87 ± 0.07) than younger ones (0.93 ± 0.04, P < 0.01), without significant differences in GOR. EAR (NES: 0.92 ± 0.06, ET: 0.86 ± 0.06, RS: 0.89 ± 0.09) significantly differed among the three strabismus groups (P = 0.02: post-hoc test: NES vs. ET, P = 0.02; NES vs. RS, P = 0.49; RS vs. ET, P = 0.67), but no significant differences in GOR were found (P = 0.12). Conclusions Among patients with acquired strabismus and high myopia, women, older patients, and those with esotropia exhibit a smaller EAR and longer sphere shape with AL as the major axis. The parameter EAR might be useful for evaluating the pathogenesis of strabismus associated with high myopia. 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.

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.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 Pediatric Severe Febrile Thrombocytopenia Syndrome: A Case Report and Literature Review 401 405 EN Yusuke Toyota Department of Pediatrics, NHO Iwakuni Clinical Center Kazuhiro Uda Department of Pediatrics, NHO Iwakuni Clinical Center Komei Shirabe Yamaguchi Prefectural Institute of Public Health and Environment Tadashi Moriwake Department of Pediatrics, NHO Iwakuni Clinical Center Case Report 10.18926/AMO/67664 Severe febrile thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease that is endemic in parts of eastern Asia. Few pediatric cases have been reported. We describe a case of SFTS in a seven-year-old girl who presented with prolonged fever and gastrointestinal symptoms. Leukopenia and thrombocytopenia on hematology, and a history of outdoor activity led us to diagnose SFTS, although the patient had no tick bite marks. We also review the literature and discuss the characteristics of pediatric SFTS. Physicians should consider SFTS in the differential diagnosis of fever with thrombocytopenia in children living in endemic areas. 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 Factors Affecting Dynamic Postural Control Ability in Adolescent Idiopathic Scoliosis 357 362 EN Ryoko Yamawaki Division of Physical Medicine and Rehabilitation, Okayama University Yoshiaki Oda Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shuhei Yamane Division of Physical Medicine and Rehabilitation, Okayama University Koji Uotani Department of Orthopaedic Surgery, Okayama University Haruo Misawa Ryusoh Orthopaedic Hospital Yoshimi Katayama Division of Physical Medicine and Rehabilitation, Okayama University Masanori Hamada Division of Physical Medicine and Rehabilitation, Okayama University Toshifumi Ozaki Division of Physical Medicine and Rehabilitation, Okayama University Original Article 10.18926/AMO/67655 Research on postural control in patients with adolescent idiopathic scoliosis (AIS) has focused on static postural control, with few studies assessing dynamic postural control. We aimed to identify factors affecting index of postural stability (IPS), a dynamic postural control parameter, in patients with AIS. The participants comprised 50 female patients with AIS. We measured the IPS using stabilometry to evaluate dynamic postural control ability. We investigated age of the participants, major curve position (thoracic or thoracolumbar/lumbar), Cobb angle, and coronal balance. We then assessed the relationships between stabilometry parameters and other variables. IPS was analyzed with a linear regression model. Coronal balance, major curve position, and age each correlated with dynamic postural control ability. The Cobb angle showed no correlation with any of the parameters. Our results offer new insights into the assessment of postural control in patients with AIS. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0040-5752 137 9 2024 Mutations in starch BRANCHING ENZYME 2a suppress the traits caused by the loss of ISOAMYLASE1 in barley 212 EN Ryo Matsushima Institute of Plant Science and Resources, Okayama University Hiroshi Hisano Institute of Plant Science and Resources, Okayama University June-Sik Kim Institute of Plant Science and Resources, Okayama University Rose McNelly John Innes Centre, Norwich Research Park Naoko F. Oitome Department of Biological Production, Akita Prefectural University David Seung John Innes Centre, Norwich Research Park Naoko Fujita Department of Biological Production, Akita Prefectural University Kazuhiro Sato Institute of Plant Science and Resources, Okayama University The genetic interactions among starch biosynthesis genes can be exploited to alter starch properties, but they remain poorly understood due to the various combinations of mutations to be tested. Here, we isolated two novel barley mutants defective in starch BRANCHING ENZYME 2a (hvbe2a-1 and hvbe2a-2) based on the starch granule (SG) morphology. Both hvbe2a mutants showed elongated SGs in the endosperm and increased resistant starch content. hvbe2a-1 had a base change in HvBE2a gene, substituting the amino acid essential for its enzyme activity, while hvbe2a-2 is completely missing HvBE2a due to a chromosomal deletion. Further genetic crosses with barley isoamylase1 mutants (hvisa1) revealed that both hvbe2a mutations could suppress defects in endosperm caused by hvisa1, such as reduction in starch, increase in phytoglycogen, and changes in the glucan chain length distribution. Remarkably, hvbe2a mutations also transformed the endosperm SG morphology from the compound SG caused by hvisa1 to bimodal simple SGs, resembling that of wild-type barley. The suppressive impact was in competition with floury endosperm 6 mutation (hvflo6), which could enhance the phenotype of hvisa1 in the endosperm. In contrast, the compound SG formation induced by the hvflo6 hvisa1 mutation in pollen was not suppressed by hvbe2a mutations. Our findings provide new insights into genetic interactions in the starch biosynthetic pathway, demonstrating how specific genetic alterations can influence starch properties and SG morphology, with potential applications in cereal breeding for desired starch properties. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0743-7463 40 32 2024 Effect of Droplet-Removal Processes on Fog-Harvesting Performance on Wettability-Controlled Wire Array with Staggered Arrangement 16994 17000 EN Yutaka Yamada Faculty of Environmental, Life, Natural Science and Technology, Okayama University Junya Oka Graduate School of Natural Science and Technology, Okayama University Kazuma Isobe Faculty of Environmental, Life, Natural Science and Technology, Okayama University Akihiko Horibe Faculty of Environmental, Life, Natural Science and Technology, Okayama University Development of freshwater resources is vital to overcoming severe worldwide water scarcity. Fog harvesting has attracted attention as a candidate technology that can be used to obtain fresh water from a stream of foggy air without energy input. Drainage of captured droplets from fog harvesters is necessary to maintain the permeability of harp-shaped harvesters. In the present study, we investigated the effect of the droplet-removal process on the amount of water harvested using a harvester constructed by wettability-controlled wires with an alternating and staggered arrangement. Droplet transfer from hydrophobic to hydrophilic wires, located upstream and downstream of the fog flow, respectively, was observed with a fog velocity greater than 1.5 m/s. The proportion of harvesting resulting from droplet transfer exceeded 30% of the total, and it reflected more than 20% increase of the harvesting performance compared with that of a harvester with wires of the same wettability: this value varied with the adhesive property of the wires and fog velocity. Scaled-up and multilayered harvesters were developed to enhance harvesting performance. We demonstrated certain enhancements under multilayered conditions and obtained 15.99 g/30 min as the maximum harvested amount, which corresponds to 13.3% of the liquid contained in the fog stream and is enhanced by 10% compared with that without droplet transfer. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 14 1 2024 Training high-performance deep learning classifier for diagnosis in oral cytology using diverse annotations 17591 EN Shintaro Sukegawa Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Futa Tanaka Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takeshi Hara Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University Takanaga Ochiai Division of Oral Pathogenesis and Disease Control, Department of Oral Pathology, Asahi University School of Dentistry Katsumitsu Shimada Department of Oral Pathology, Graduate School of Oral Medicine, Matsumoto Dental University Yuta Inoue Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University Yoshihiro Taki Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University Fumi Nakai Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine Yasuhiro Nakai Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine Takanori Ishihama Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine Ryo Miyazaki Stony Brook Cancer Center, Stony Brook University Satoshi Murakami Department of Oral Pathology, Graduate School of Oral Medicine, Matsumoto Dental University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Minoru Miyake Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine The uncertainty of true labels in medical images hinders diagnosis owing to the variability across professionals when applying deep learning models. We used deep learning to obtain an optimal convolutional neural network (CNN) by adequately annotating data for oral exfoliative cytology considering labels from multiple oral pathologists. Six whole-slide images were processed using QuPath for segmenting them into tiles. The images were labeled by three oral pathologists, resulting in 14,535 images with the corresponding pathologists' annotations. Data from three pathologists who provided the same diagnosis were labeled as ground truth (GT) and used for testing. We investigated six models trained using the annotations of (1) pathologist A, (2) pathologist B, (3) pathologist C, (4) GT, (5) majority voting, and (6) a probabilistic model. We divided the test by cross-validation per slide dataset and examined the classification performance of the CNN with a ResNet50 baseline. Statistical evaluation was performed repeatedly and independently using every slide 10 times as test data. For the area under the curve, three cases showed the highest values (0.861, 0.955, and 0.991) for the probabilistic model. Regarding accuracy, two cases showed the highest values (0.988 and 0.967). For the models using the pathologists and GT annotations, many slides showed very low accuracy and large variations across tests. Hence, the classifier trained with probabilistic labels provided the optimal CNN for oral exfoliative cytology considering diagnoses from multiple pathologists. These results may lead to trusted medical artificial intelligence solutions that reflect diverse diagnoses of various professionals. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 29 10 2024 Re-administration of platinum-based chemotherapy for recurrent endometrial cancer: an ancillary analysis of the SGSG-012/GOTIC-004/Intergroup study 1594 1601 EN Shoji Nagao Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin Nishio Department of Obstetrics and Gynecology, Kurume University School of Medicine Kazuhiro Takehara Department of Gynecologic Oncology, NHO Shikoku Cancer Center Shinya Sato Department of Obstetrics and Gynecology, Tottori University Toyomi Satoh Department of Obstetrics and Gynecology, Institute of Medicine, University of Tsukuba Muneaki Shimada Department of Gynecology, Tohoku University Hospital Satoshi Yamaguchi Department of Medical Oncology, Hyogo Cancer Center Hiroshi Tanabe Department of Obstetrics and Gynecology, Jikei University School of Medicine Masashi Takano Department of Obstetrics and Gynecology, National Defense Medical College Kouji Horie Department of Gynecologic Oncology, Saitama Cancer Center Yuji Takei Department of Obstetrics and Gynecology, Jichi Medical University Yuichi Imai Department of Obstetrics and Gynecology, Yokohama City University Hospital Yumi Hibino Department of Gynecologic Oncology, NHO Shikoku Cancer Center Kosei Hasegawa Department of Gynecologic Oncology, Saitama Medical University International Medical Center Munetaka Takekuma Department of Gynecology, Shizuoka Cancer Center Kazuto Nakamura Department of Gynecology, Gunma Prefectural Cancer Center Hirokuni Takano Department of Obstetrics and Gynecology, Jikei University School of Medicine Keiichi Fujiwara Department of Gynecologic Oncology, Saitama Medical University International Medical Center Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background We previously demonstrated the applicability of the concept of “platinum sensitivity” in recurrent endometrial cancer. Although immune checkpoint inhibitors have been widely incorporated into endometrial cancer treatment, the debate continues regarding treatment options in patients with recurrent endometrial cancer who have previously received platinum-based chemotherapy. In this study, we assessed the duration of response to secondary platinum-based treatment using pooled data from the SGSG-012/GOTIC-004/Intergroup study. Methods Among the 279 participants in the SGSG-012/GOTIC-004/Intergroup study wherein platinum-based chemotherapy was re-administered for managing recurrent endometrial cancer between January 2005 and December 2009, 130 (47%) responded to chemotherapy. We compared the relationship between platinum-free interval and duration of secondary platinum-based treatment using pooled data. Results In 40 patients (31%), the duration of response to secondary platinum-based treatment exceeded the platinum-free interval. The duration of response to secondary platinum-based treatment exceeded 12 months in 51 patients (39%) [platinum-free interval: < 12 months, 14/48 (29%); 12–23 months, 18/43 (42%); 24–35 months, 8/19 (42%); ≥ 36 months, 11/20 (55%)]. In particular, in eight patients (6%), the duration of response to secondary platinum-based treatment exceeded 36 months [platinum-free interval: < 12 months, 3/48 (6%); 12–23 months, 0/19 (0%); 24–35 months, 2/19 (11%); ≥ 36 months, 3/20 (15%)]. Conclusions Re-administration of platinum-based chemotherapy for recurrent endometrial cancer may result in a long-term response exceeding the platinum-free interval in some patients. Even in the current situation, where immune checkpoint inhibitors have been introduced, re-administration of platinum-based chemotherapy is worth considering. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0172-0643 46 6 2024 Pulmonary Flow Management by Combination Therapy of Hemostatic Clipping and Balloon Angioplasty for Right Ventricular-Pulmonary Artery Shunt in Hypoplastic Left Heart Syndrome 1635 1642 EN Yusuke Shigemitsu Department of Pediatrics, Okayama University Hospital Maiko Kondo Department of Pediatrics, Okayama University Hospital Yoshihiko Kurita Department of Pediatrics, Okayama University Hospital Yosuke Fukushima Department of Pediatrics, Okayama University Hospital Yuya Kawamoto Department of Pediatrics, Okayama University Hospital Kenta Hirai Department of Pediatrics, Okayama University Hospital Mayuko Hara Department of Pediatrics, Okayama University Hospital Tomoyuki Kanazawa Department of Pediatric Anesthesiology, Okayama University Hospital Tatsuo Iwasaki Department of Pediatric Anesthesiology, Okayama University Hospital Shingo Kasahara Department of Pediatric Anesthesiology, Okayama University Hospital Koichi Kataoka Department of Cardiovascular Surgery, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Hospital Kenji Baba Department of Pediatrics, Okayama University Hospital Controlling pulmonary blood flow in patients who have undergone Norwood palliation, especially early postoperatively, is challenging due to a change in the balance of systemic and pulmonary vascular resistance. We applied a combination therapy of clipping and balloon angioplasty for right ventricle—pulmonary artery (RV-PA) shunt to control pulmonary blood flow, but the influence of the combination therapy on the PA condition is uncertain. Retrospectively analysis was conducted of all infants with hypoplastic left heart syndrome who had undergone Norwood palliation with RV-PA shunt at Okayama University Hospital from January 2008 to September 2022. A total of 50 consecutive patients underwent Norwood palliation with RV-PA shunt in this study period. Of them, 29 patients underwent RV-PA shunt flow clipping, and the remaining 21 had unclipped RV-PA shunt. Twenty-three patients underwent balloon angioplasty for RV-PA shunt with clips. After balloon angioplasty, oxygen saturation significantly increased from 69 (59–76)% to 80 (72–86)% (p < 0.001), and the narrowest portion of the clipped conduit significantly improved from 2.8 (1.8–3.4) to 3.8 (2.9–4.6) mm (p < 0.001). In cardiac catheterizations prior to Bidirectional cavo-pulmonary shunt (BCPS), there were no significant differences in pulmonary-to-systemic flow ratio (Qp/Qs), ventricular end-diastolic pressure, Nakata index, arterial saturation, mean pulmonary artery pressure and pulmonary vascular resistance index. On the other hand, in Cardiac catheterizations prior to Fontan, Nakata index was larger in the clipped group (p = 0.02). There was no statistically significant difference in the 5-year survival between the two groups (clipped group 96%, unclipped group 74%, log-rank test: p = 0.13). At least, our combination therapy of clipping and balloon angioplasty for RV-PA shunt did not negatively impact PA growth. Although there is a trend toward better but not statistically significant difference in outcomes in the clipped group compared to the non-clipped group, this treatment strategy may play an important role in improving outcomes in hypoplastic left heart syndrome. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1613-4125 68 15 2024 Unabsorbed Fecal Fat Content Correlates with a Reduction of Immunoglobulin a Coating of Gut Bacteria in High‐Lard Diet‐Fed Mice 2400078 EN Emiko Katsumata Graduate School of Environmental and Life Science, Okayama University Takeshi Tsuruta Graduate School of Environmental and Life Science, Okayama University Kei Sonoyama Research Faculty of Agriculture, Hokkaido University Takashi Yoshida TAIYO YUSHI Corporation Mio Sasaki TAIYO YUSHI Corporation Mao Teraoka Graduate School of Environmental and Life Science, Okayama University Tianyang Wang Graduate School of Environmental and Life Science, Okayama University Naoki Nishino Graduate School of Environmental and Life Science, Okayama University Scope: Immunoglobulin A (IgA) selectively coats gut bacteria and contributes to regulatory functions in gastrointestinal inflammation and glucose metabolism. Excess intake of lard leads to decrease in the IgA coating of gut bacteria, although the underlying mechanisms remain unknown. This study validates how unabsorbed fat derived from a high-lard diet in the gut affects the IgA coating of bacteria, as assessed in mouse models using three types of dietary fat (lard, medium-, and long-chain triglycerides [MLCTs], and medium-chain triglycerides [MCTs]) exhibiting different digestibilities. Methods and results: C57BL/6J mice are maintained on diets containing lard, MLCTs, or MCTs at 7% or 30% w/w for 10 weeks (n = 6 per group). The fecal fatty acid concentration is measured to quantify unabsorbed fat content. The ratio of IgA-coated bacteria to total bacteria (IgA coating ratio) in the feces is measured by flow cytometry. Compared to lard-fed mice, MLCT- and MCT-fed mice exhibit lower fecal concentrations of palmitic acid, stearic acid, and oleic acid and higher IgA coating ratios at both 7% and 30% dietary fat, and these parameters exhibit significant negative correlations. Conclusion: Unabsorbed fat content in the gut may result in attenuated IgA coating of bacteria in high-lard diet-fed mice. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0385-2407 51 8 2024 The treatment effect of endovascular therapy for chronic limb‐threatening ischemia with systemic sclerosis 1108 1112 EN Yoshihiro Matsuda Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Miyake Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hironobu Toda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kota Tachibana Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hayato Nomura Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoji Hirai Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshio Kawakami Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoya Sakoda Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Morizane Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Systemic sclerosis (SSc) is a collagen disease with immune abnormalities, vasculopathy, and fibrosis. Ca blockers and prostaglandins are used to treat peripheral circulatory disturbances. Chronic limb-threatening ischemia (CLTI) is a disease characterized by extremity ulcers, necrosis, and pain due to limb ischemia. Since only a few patients present with coexistence of CLTI and SSc, the treatment outcomes of revascularization in these cases are unknown. In this study, we evaluated the clinical characteristics and treatment outcomes of seven patients with CLTI and SSc, and 35 patients with uncomplicated CLTI who were hospitalized from 2012 to 2022. A higher proportion of patients with uncomplicated CLTI had diabetes and male. There were no significant differences in the age at which ischemic ulceration occurred, other comorbidities, or in treatments, including antimicrobial agents, revascularization and amputation, improvement of pain, and the survival time from ulcer onset between the two subgroups. EVT or amputation was performed in six or two of the seven patients with CLTI and SSc, respectively. Among those who underwent EVT, 33% (2/6) achieved epithelialization and 67% (4/6) experienced pain relief. These results suggest that the revascularization in cases with CLTI and SSc should consider factors such as infection and general condition, since revascularization improve the pain of these patients. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2045-7758 14 6 2024 Heterospecific interaction in two beetle species: Males with weapons decrease the reproductive success of species with weaponless males e11518 EN Rui Onishi Graduate School of Environmental, Natural Science, and Technology, Okayama University Kentarou Matsumura Graduate School of Environmental, Natural Science, and Technology, Okayama University Many species often show male-male combat for mating opportunities and resources within the species. Sexual selection through this radical combat leads to the evolution of males with exaggerated traits used as weapons, such as horns or mandibles, that often result in victory during combat. However, heterospecific interaction due to errors in species identification has often been observed, which results in decreased mating opportunities within the same species and fewer fertilized eggs. Males with exaggerated weapons may show dominance in resource acquisition over males without weapons and may decrease the reproductive success of the latter due to competition between the two. However, few studies have examined heterospecific interaction focusing on males with or without weapons. In this study, we investigated the effects of the male weapon on reproductive traits in heterospecific interaction in two species: the broad-horned flour beetle (Gnatocerus cornutus), in which males have exaggerated weapon traits; and the red flour beetle (Tribolium castaneum), in which males have no weapon traits. Both species are closely related and use the same food resources. G. cornutus males interfered with the resource acquisition and reproductive opportunities of T. castaneum by attacking T. castaneum. The reproductive success of T. castaneum decreased when they cohabited with G. cornutus males. These findings show that male weapon traits, which are important for sexual selection within the same species, can also greatly influence reproduction in other species. No potential conflict of interest relevant to this article was reported.

Elsevier Taiwan Acta Medica Okayama 1875-9572 65 3 2024 Postnatal longitudinal analysis of serum nitric oxide and eosinophil counts in extremely preterm infants 276 281 EN Hirokazu Watanabe Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Yosuke Washio Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Kei Tamai Department of Neonatology, Okayama Medical Center, National Hospital Organization Daisaku Morimoto Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Tomoka Okamura Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Junko Yoshimoto Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Hidehiko Nakanishi Department of Neonatology, Maternal and Perinatal Center, Tokyo Women’s Medical University Misao Kageyama Department of Neonatology, Okayama Medical Center, National Hospital Organization Atsushi Uchiyama Department of Neonatology, Maternal and Perinatal Center, Tokyo Women’s Medical University Hirokazu Tsukahara Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Satoshi Kusuda Department of Neonatology, Maternal and Perinatal Center, Tokyo Women’s Medical University Background: Nitric oxide (NO) may be related to the pathogenesis of several morbidities in extremely preterm infants, including late-onset adrenal insufficiency. However, eosinophilia is observed under pathological conditions with adrenal insufficiency. Therefore, this study explored postnatal changes in NO levels and eosinophil counts in extremely preterm infants with and without morbidities. Methods: Nineteen extremely preterm infants with a median gestational age of 27.0 weeks and median birth weight of 888 g were enrolled in this study. Serum levels of nitrogen oxides (NOx) and peripheral blood eosinophil counts were measured at birth and every 2 weeks thereafter. Morbidities of the study group were diagnosed using a single criterion. Results: Serum NOx levels (mean ± standard deviation) were 22.5 ± 14.9 μmol/L, 51.2 ± 23.7 μmol/L, 42.4 ± 15.2 μmol/L, and 33.8 ± 9.4 μmol/L at birth and 2, 4, and 6 weeks of age, respectively. The serum NOx level at 2 weeks of age was significantly higher than that at birth and 6 weeks of age. Eosinophil counts, which increase with adrenal insufficiency, were measured simultaneously and were 145 ± 199/μL, 613 ± 625/μL, 466 ± 375/μL, and 292 ± 228/μL at birth and 2, 4, and 6 weeks of age, respectively. These values showed that the eosinophil count was significantly higher at 2 weeks of age than at birth and 6 weeks of age. The serum NOx level of infants without chorioamnionitis was significantly increased at 4 weeks of age, and the eosinophil count of infants with necrotizing enterocolitis was significantly increased at 2 weeks of age. No correlation with the NOx level or eosinophil count was observed in infants with late-onset circulatory collapse. Conclusion: The postnatal serum NOx level and eosinophil count were significantly correlated with each other and peaked at 2 weeks of age. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 3 2024 A Case of Gallbladder Metastasis of Malignant Melanoma 291 294 EN Hitoshi Minagi Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Hideki Aoki Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Susumu Doita Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Eiki Miyake Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Toshihiro Ogawa Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Fumitaka Taniguchi Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Megumi Watanabe Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Takashi Arata Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Koh Katsuda Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Kohji Tanakaya Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Case Report 10.18926/AMO/67205 In the clinical course of malignant melanoma, which can metastasize to multiple organs, gallbladder metastases are rarely detected. A 69-year-old man who underwent resection of a primary malignant melanoma was subsequently treated with nivolumab for lung metastases and achieved complete response. Seven years after surgery, multiple nodules were found in the gallbladder, and he underwent laparoscopic cholecystectomy. The postoperative diagnosis was metastases of malignant melanoma. He has been recurrence-free 8 months after surgery. If radical resection is possible, such surgery should be performed for gallbladder metastases found in patients with other controlled lesions of malignant melanoma. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 3 2024 The Impact of Reduced Skeletal Muscle Mass on Patients with Knee Osteoarthritis 245 250 EN Manabu Akagawa Department of Orthopedic Surgery, Omagari Kousei Medical Center Hidetomo Saito Department of Orthopedic Surgery, Akita University Graduate School of Medicine Yasuhiro Takahashi Department of Orthopedic Surgery, Omagari Kousei Medical Center Yosuke Iwamoto Department of Orthopedic Surgery, Omagari Kousei Medical Center Junpei Iida Department of Orthopedic Surgery, Omagari Kousei Medical Center Takayuki Yoshikawa Department of Orthopedic Surgery, Omagari Kousei Medical Center Toshiki Abe Department of Orthopedic Surgery, Omagari Kousei Medical Center Kimio Saito Department of Orthopedic Surgery, Akita University Graduate School of Medicine Hiroaki Kijima Department of Orthopedic Surgery, Akita University Graduate School of Medicine Yuji Kasukawa Department of Orthopedic Surgery, Akita University Graduate School of Medicine Michio Hongo Department of Orthopedic Surgery, Akita University Graduate School of Medicine Naohisa Miyakoshi Department of Orthopedic Surgery, Akita University Graduate School of Medicine Original Article 10.18926/AMO/67199 Although several studies have suggested a possible association between sarcopenia and knee osteoarthritis (OA) in the elderly, there remains no definitive evidence. Recently, however, the serum creatinine/cystatin C ratio (sarcopenia index: SI) was reported to correlate with skeletal muscle mass. The present retrospective study therefore investigated the impact of reduced skeletal muscle mass on advanced knee OA using SI. In 55 individuals scheduled for knee osteotomy or knee arthroplasty, correlations between SI and patient-reported outcomes such as the Knee Society Score (KSS), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Oxford Knee Score (OKS) were explored. Significant associations were found between SI and the KSS functional activity score (β=0.37; p=0.022), KOOS subscale for activities of daily living (β=0.42; p=0.0096), and OKS (β=0.42; p=0.0095). This study underscores the role of reduced muscle mass in functional outcomes and introduces SI as a valuable marker for assessing muscle loss in knee OA patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 3 2024 Assessment of a New Elbow Joint Positioning Method Using Area Detector Computed Tomography 215 225 EN Takuya Akagawa Department of Radiological Technology, Tokushima Red Cross Hospital Ryohei Fukui Department of Radiological Technology, Faculty of Health Sciences, Okayama University Katsuhiro Kida Department of Radiological Technology, Faculty of Health Sciences, Okayama University Ryutaro Matsuura Department of Radiological Technology, Faculty of Health Sciences, Okayama University Makoto Shimada Department of Radiology, Osaka International Cancer Institute Mitsuhiro Kinoshita Department of Radiology, Tokushima Red Cross Hospital Yoko Akagawa Department of Radiology, Tokushima Red Cross Hospital Sachiko Goto Department of Radiological Technology, Faculty of Health Sciences, Okayama University Original Article 10.18926/AMO/67196 We propose a sitting position that achieves both high image quality and a reduced radiation dose in elbow joint imaging by area detector computed tomography (ADCT), and we compared it with the ‘superman’ and supine positions. The volumetric CT dose index (CTDIvol) for the sitting, superman, and supine positions were 2.7, 8.0, and 20.0 mGy and the dose length products (DLPs) were 43.4, 204.7, and 584.8 mGy • cm, respectively. In the task-based transfer function (TTF), the highest value was obtained for the sitting position in both bone and soft tissue images. The noise power spectrum (NPS) of bone images showed that the superman position had the lowest value up to approx. 1.1 cycles/mm or lower, whereas the sitting position had the lowest value when the NPS was greater than approx. 1.1 cycles/mm. The overall image quality in an observer study resulted in the following median Likert scores for Readers 1 and 2: 5.0 and 5.0 for the sitting position, 4.0 and 3.5 for the superman position, and 4.0 and 2.0 for the supine position. These results indicate that our proposed sitting position with ADCT of the elbow joint can provide superior image quality and allow lower radiation doses compared to the superman and supine positions. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-2607 12 5 2024 Isolation of Vibrio cholerae and Vibrio vulnificus from Estuarine Waters, and Genotyping of V. vulnificus Isolates Using Loop-Mediated Isothermal Amplification 877 EN Shin-Ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Megumi Kurata Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Riho Hirose Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaya Yoshikawa Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yong Liang Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yosuke Yamagishi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tamaki Mizuno Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Bacteria in the genus Vibrio are ubiquitous in estuarine and coastal waters. Some species (including Vibrio cholerae and Vibrio vulnificus) are known human pathogens causing ailments like cholera, diarrhea, or septicemia. Notably, V. vulnificus can also cause a severe systemic infection (known as vibriosis) in eels raised in aquaculture facilities. Water samples were periodically collected from the estuary of the Asahi River, located in the southern part of Okayama City, Japan. These samples were directly plated onto CHROMagar Vibrio plates, and colonies displaying turquoise-blue coloration were selected. Thereafter, polymerase chain reaction was used to identify V. cholerae and V. vulnificus. A total of 30 V. cholerae strains and 194 V. vulnificus strains were isolated during the warm season when the water temperature (WT) was higher than 20 degrees C. Concurrently, an increase in coliforms was observed during this period. Notably, V. vulnificus has two genotypes, designated as genotype 1 and genotype 2. Genotype 1 is pathogenic to humans, while genotype 2 is pathogenic to both humans and eels. The loop-mediated isothermal amplification method was developed to rapidly determine genotypes at a low cost. Of the 194 strains isolated, 80 (41.2%) were identified as genotype 1 strains. Among the 41 strains isolated when the WTs were higher than 28 degrees C, 25 strains (61.0%) belonged to genotype 1. In contrast, of the 32 strains isolated when the WTs were lower than 24 degrees C, 27 strains (84.4%) belonged to genotype 2. These results suggest that the distribution of the two genotypes was influenced by WT. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0003-9969 165 2024 Salivary buffering capacity is correlated with umami but not sour taste sensitivity in healthy adult Japanese subjects 106013 EN Aiko Hyodo Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ayaka Mikami Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kengo Horie Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihiro Mitoh Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuzo Ninomiya Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Seiji Iida Department of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryusuke Yoshida Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objective: Saliva serves multiple important functions crucial for maintaining a healthy oral and systemic environment. Among them, the pH buffering effect, which is primarily mediated by bicarbonate ions, helps maintain oral homeostasis by neutralizing acidity from ingested foods. Therefore, higher buffering capacity, reflecting the ability to neutralize oral acidity, may influence taste sensitivity, especially for sour taste since it involves sensing H+ ions. This study aims to explore the relationship between salivary buffering capacity and taste sensitivities to the five basic tastes in healthy adult humans. Design: Eighty seven healthy adult students participated in this study. Resting saliva volume was measured using the spitting method. The liquid colorimetric test was used to assess salivary buffering capacity. The whole-mouth taste testing method was employed to determine the recognition threshold for each tastant (NaCl, sucrose, citric acid, quinine-HCl, monosodium glutamate). Results: Taste recognition thresholds for sour taste as well as sweet, salty, and bitter tastes showed no correlation with salivary buffering capacity. Interestingly, a negative relationship was observed between recognition threshold for umami taste and salivary buffering capacity. Furthermore, a positive correlation between salivary buffering capacity and resting saliva volume was observed. Conclusions: Salivary buffering capacity primarily influences sensitivity to umami taste, but not sour and other tastes. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Fabrication of two-dimensional materials/polyimide composites by covalent bonding strategies EN YIKAI CHENG Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Proposal for diagnosis using FLAIR image aimed for pediatric MELAS with recurrent stroke-like episodes on MRI system cannot take ASL imaging. EN Makoto SHIMADA Graduate School of Health Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Assessment of a New Elbow Joint Positioning Method Using Area Detector Computed Tomography EN Takuya AKAGAWA Graduate School of Health Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Development of numerical technique and field application using integrated simulation of river flooding and inundation for disaster prevention and mitigation EN WEIJIAN HUA Graduate School of Environmental and Life Science, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 メチル水銀の毒性機序および新規障害部位の解析 EN Yuta IIJIMA 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 Percentage of low attenuation area on computed tomography detects chronic lung allograft dysfunction, especially bronchiolitis obliterans syndrome, after bilateral lung transplantation EN Yujiro KUBO 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 Postnatal longitudinal analysis of serum nitric oxide and eosinophil counts in extremely preterm infants EN Hirokazu WATANABE 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 Regression of Necrotic Lesions after Methotrexate Withdrawal in Patients with Methotrexate-Associated Lymphoproliferative Disorders: A Retrospective CT Study EN Takahiro KITAYAMA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0021-924X 174 5 2023 Direct binding of calmodulin to the cytosolic C-terminal regions of sweet/umami taste receptors 451 459 EN Atsuki Yoshida Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ayumi Ito Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Norihisa Yasui Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsuko Yamashita Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sweet and umami taste receptors recognize chemicals such as sugars and amino acids on their extracellular side and transmit signals into the cytosol of the taste cell. In contrast to ligands that act on the extracellular side of these receptors, little is known regarding the molecules that regulate receptor functions within the cytosol. In this study, we analysed the interaction between sweet and umami taste receptors and calmodulin, a representative Ca2+-dependent cytosolic regulatory protein. High prediction scores for calmodulin binding were observed on the C-terminal cytosolic side of mouse taste receptor type 1 subunit 3 (T1r3), a subunit that is common to both sweet and umami taste receptors. Pull-down assay and surface plasmon resonance analyses showed different affinities of calmodulin to the C-terminal tails of distinct T1r subtypes. Furthermore, we found that T1r3 and T1r2 showed the highest and considerable binding to calmodulin, whereas T1r1 showed weaker binding affinity. Finally, the binding of calmodulin to T1rs was consistently higher in the presence of Ca2+ than in its absence. The results suggested a possibility of the Ca2+-dependent feedback regulation process of sweet and umami taste receptor signaling by calmodulin. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0925-5710 120 1 2024 Spontaneous regression of multiple solitary plasmacytoma harboring Epstein–Barr virus: a case report and literature review 128 134 EN Wataru Kitamura Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hiroki Kobayashi Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Minori Noda Department of Otorhinolaryngology, National Hospital Organization Iwakuni Clinical Center Akiko Iseki Department of Pathology, National Hospital Organization Iwakuni Clinical Center Yumi Sato Department of Pathology, National Hospital Organization Iwakuni Clinical Center Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shoichi Kuyama Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center We report a rare case of spontaneous regression (SR) in an elderly untreated patient with multiple solitary plasmacytoma (MSP). Diagnosis of MSP was confirmed through surgical resection of the left nasal cavity mass and subsequent biopsy of the right humerus. The patient was considered ineligible for chemotherapy due to poor performance status. At 3-month post-diagnosis, the patient’s condition worsened with deteriorating bone lesions and emergence of a new serum monoclonal protein. However, these clinical findings completely disappeared at 6 months, and positron emission tomography–computed tomography at 1 year confirmed complete metabolic remission. Notably, peripheral blood lymphocyte counts were inversely correlated with tumor progression and remission. Pathological re-evaluation of the initial biopsy specimens revealed programmed cell death protein 1 (PD-1) expression in tumor-infiltrating CD8+ T cells. In addition, tumor cells were infected with Epstein–Barr virus (EBV) but were negative for programmed cell death ligand 1 (PD-L1) expression, which is the most potent immune escape mechanism in tumor cells. While the mechanism underlying SR remains unclear, our findings suggest that host immune response as well as EBV infection may contribute to SR. Further studies are needed to elucidate the clinicopathologic mechanisms of tumor regression in plasma cell neoplasms. No potential conflict of interest relevant to this article was reported.

Oxford University Press Acta Medica Okayama 0305-1048 52 10 2024 The ABCF proteins in Escherichia coli individually cope with 'hard-to-translate' nascent peptide sequences 5825 5840 EN Yuhei Chadani Faculty of Environmental, Life, Natural Science and Technology, Okayama University Shun Yamanouchi Department of Biological Sciences, Graduate School of Science, the University of Tokyo Eri Uemura Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology Kohei Yamasaki Faculty of Science, Okayama University Tatsuya Niwa Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology Toma Ikeda School of Life Science and Technology, Tokyo Institute of Technology Miku Kurihara School of Life Science and Technology, Tokyo Institute of Technology Wataru Iwasaki Department of Biological Sciences, Graduate School of Science, the University of Tokyo Hideki Taguchi Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology Organisms possess a wide variety of proteins with diverse amino acid sequences, and their synthesis relies on the ribosome. Empirical observations have led to the misconception that ribosomes are robust protein factories, but in reality, they have several weaknesses. For instance, ribosomes stall during the translation of the proline-rich sequences, but the elongation factor EF-P assists in synthesizing proteins containing the poly-proline sequences. Thus, living organisms have evolved to expand the translation capability of ribosomes through the acquisition of translation elongation factors. In this study, we have revealed that Escherichia coli ATP-Binding Cassette family-F (ABCF) proteins, YheS, YbiT, EttA and Uup, individually cope with various problematic nascent peptide sequences within the exit tunnel. The correspondence between noncanonical translations and ABCFs was YheS for the translational arrest by nascent SecM, YbiT for poly-basic sequence-dependent stalling and poly-acidic sequence-dependent intrinsic ribosome destabilization (IRD), EttA for IRD at the early stage of elongation, and Uup for poly-proline-dependent stalling. Our results suggest that ATP hydrolysis-coupled structural rearrangement and the interdomain linker sequence are pivotal for handling 'hard-to-translate' nascent peptides. Our study highlights a new aspect of ABCF proteins to reduce the potential risks that are encoded within the nascent peptide sequences. Graphical Abstract No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1201-9712 141 2024 Vibriosis in South Asia: A systematic review and meta-analysis 106955 EN Basilua Andre Muzembo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kei Kitahara Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ayumu Ohno Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Januka Khatiwada Social Work Institute Shanta Dutta Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases Shin-Ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: South Asia remains home to foodborne diseases caused by the Vibrio species. We aimed to compile and update information on the epidemiology of vibriosis in South Asia. Methods: For this systematic review and meta-analysis, we searched PubMed, Web of Science, EMBASE, and Google Scholar for studies related to vibriosis in South Asia published up to May 2023. A random-effects meta-analysis was used to estimate the pooled isolation rate of non-cholera-causing Vibrio species. Results: In total, 38 studies were included. Seven of these were case reports and 22 were included in the meta-analysis. The reported vibriosis cases were caused by non-O1/non-O139 V. cholerae, V. parahaemolyticus, V. fluvialis, and V. vulnificus. The overall pooled isolation rate was 4.0% (95% confidence interval [CI] 3.0-5.0%) in patients with diarrhea. Heterogeneity was high (I-2 = 98.0%). The isolation rate of non-O1/non-O139 V. cholerae, V. parahaemolyticus, and V. fluvialis were 9.0 (95% CI 7.0-10.0%), 1.0 (95% CI 1.0-2.0%), and 2.0 (95% CI: 1.0-3.0%), respectively. Regarding V. parahaemolyticus, O3:K6 was the most frequently isolated serotype. Cases peaked during summer. Several studies reported antibiotic-resistant strains and those harboring extended-spectrum beta-lactamases genes. Conclusions: This study demonstrates a high burden of infections caused by non-cholera-causing Vibrio species in South Asia. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0910-8327 38 9 2023 Prognostic value of the liver fibrosis marker fibrosis-5 index in patients with severe isolated tricuspid regurgitation: comparison with fibrosis-4 index 1181 1189 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 Machiko Tanakaya Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center Takaaki Saito Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center Yusuke Katayama Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center Satoru Sakuragi Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center Yoichi Takaya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The fibrosis-4 index (FIB4), a liver fibrosis maker, has been shown to be associated with the prognosis in patients with severe isolated tricuspid regurgitation (TR). Recent study showed that the fibrosis-5 index (FIB5), which was calculated by albumin, alkaline phosphatase, aspartate transaminase, alanine aminotransferase and platelet count, had better prognostic value than FIB4 in patients with heart failure. The aim of this study was to evaluate the usefulness of FIB5 index for predicting prognosis in patients with severe isolated TR and compare the prognostic value between the FIB4 and the FIB5 in those patients. This was a dual-center, retrospective study. 113 consecutive outpatients with severe isolated TR (mean age, 65.8 years; 47.8% male) were analyzed. Major adverse cardiovascular events (MACEs) were defined as the composite of cardiovascular death, hospitalization for heart failure, myocardial infarction, and stroke. During a median follow-up of 3.0 years, 41 MACEs occurred. Patients with MACEs had a lower the FIB5 than patients without MACEs. The multivariate Cox analysis revealed that the FIB5 < -4.30 was significantly associated with higher incidence of MACEs after adjusted by confounding factors. Receiver-operating characteristic curve analyses showed that prognostic values did not differ between the FIB5 and the FIB4 in whole patients and in patients aged ≥ 70 years; while, in patients aged < 70 years, the FIB5 had better prognostic value than the FIB4. The FIB5 may be a useful predictor of MACEs in patients with severe isolated TR. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1612-9059 20 3 2023 Outcomes of solitary postoperative recurrence of esophageal squamous cell carcinoma diagnosed with FDG-PET/CT and treated with definitive radiation therapy 548 556 EN Hiroki Ihara Department of Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kotaro Yoshio Department of Proton Beam Therapy, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunsuke Tanabe Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichi Sugiyama Department of Proton Beam Therapy, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masashi Hashimoto Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoaki Maeda Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinsuke Akagi Department of Epidemiology, 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 Kazuhiro Noma Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takao Hiraki Department of Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Surgical resection of esophageal cancer is frequently performed to achieve a complete cure. However, the postoperative recurrence rate is 36.8–42.5%, leading to poor prognosis. Radiation therapy has been used to treat recurrences; solitary recurrence has been proposed as a prognostic factor for radiation therapy, though its significance is unclear. 18F-fluorodeoxyglucose positron emission tomography is a highly accurate diagnostic modality for esophageal cancer. This retrospective study aimed to analyze the outcomes of solitary postoperative recurrences of esophageal squamous cell carcinoma diagnosed with 18F-fluorodeoxyglucose positron emission tomography and treated with definitive radiation therapy. Methods We examined 27 patients who underwent definitive radiation therapy for single or multiple postoperative recurrences of esophageal squamous cell carcinoma between May 2015 and April 2021. 18F-fluorodeoxyglucose positron emission tomography/computed tomography was performed within 3 months before the commencement of radiation therapy. Kaplan–Meier, univariate, and multivariate analyses were performed to examine the overall survival and identify potential prognostic factors. Results The 1-, 2-, and 3-year overall survival rates were 85.2%, 62.6%, and 47.3%, respectively, and solitary recurrence was the only significant factor associated with overall survival (P = 0.003). The 1-, 2-, and 3-year overall survival rates in patients with solitary recurrence were 91.7%, 80.2%, and 80.2%, respectively, and in patients with multiple recurrences they were 80.0%, 50.3%, and 25.1%, respectively. Multivariate analysis also showed solitary recurrence as a significant factor for overall survival. Conclusions When diagnosed with 18F-fluorodeoxyglucose positron emission tomography/computed tomography, solitary recurrence appears to have a more favorable prognosis than multiple recurrences. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 A Case of Gallbladder Cancer with Trousseau Syndrome Successfully Treated Using Radical Resection 201 204 EN Akari Masunaga Department of Gastroenterological Surgery, Kochi Health Sciences Center Motoyasu Tabuchi Department of Gastroenterological Surgery, Kochi Health Sciences Center Shinya Sakamoto Department of Gastroenterological Surgery, Kochi Health Sciences Center Rika Yoshimatsu Department of Radiology, Kochi Health Sciences Center Manabu Matsumoto Department of Radiology, Kochi Health Sciences Center Jun Iwata Department of Diagnostic Pathology, Kochi Health Sciences Center Takehiro Okabayashi Department of Gastroenterological Surgery, Kochi Health Sciences Center Case Report 10.18926/AMO/66931 Trousseau syndrome is characterized by cancer-associated systemic thrombosis. We describe the first case of a successfully treated gallbladder adenocarcinoma accompanied by Trousseau syndrome. A 66-year-old woman presented with right hemiplegia. Magnetic resonance imaging identified multiple cerebral infarctions. Her serum carbohydrate antigen 19-9 and D-dimer levels were markedly elevated, and a gallbladder tumor was detected via abdominal computed tomography. Venous ultrasonography of the lower limbs revealed a deep venous thrombus in the right peroneal vein. These findings suggested that the brain infarctions were likely caused by Trousseau syndrome associated with her gallbladder cancer. Radical resection of the gallbladder tumor was performed. The resected gallbladder was filled with mucus and was pathologically diagnosed as an adenocarcinoma. Her postoperative course was uneventful, and she received a one-year course of adjuvant therapy with oral S-1. No cancer recurrence or thrombosis was noted 26 months postoperatively. Despite concurrent Trousseau syndrome, a radical cure of the primary tumor and thrombosis could be achieved with the appropriate treatment. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 The Impact of Light Touch and Pin Prick on Functional Outcomes in Patients with Traumatic Spinal Cord Injury 163 170 EN Takayuki Deguchi Department of Rehabilitation, Kagawa Rosai Hospital Kanae Kanda Department of Public Health, Faculty of Medicine, Kagawa University Kazunari Furusawa Department of Rehabilitation Medicine, Kibikogen Rehabilitation Center for Employment Injuries Nlandu Roger Ngatu Department of Public Health, Faculty of Medicine, Kagawa University Tomohiro Hirao Department of Public Health, Faculty of Medicine, Kagawa University Original Article 10.18926/AMO/66925 A spinal cord injury (SCI) can cause severe lifelong functional disability and profoundly affect an individual’s daily life. We investigated the prediction of patients’ post-SCI functional outcomes by evaluating sensory scores rather than motor scores, as the latter’s association with functional outcomes is well established. We examined patients’ responses to a light touch (LT) and pin prick (PP) at admission and the response data’s usefulness as predictors of functional outcomes (i.e., ability to perform activities of daily living) at discharge. This exploratory observational study used data from the Japanese National Spinal Cord Injury Database (SCI-J). Data from 3,676 patients who met the inclusion criteria and were admitted for an SCI between 1997 and 2020 were analyzed. The motor score of the Functional Independence Measure (mFIM) at discharge was used as an index of functional outcome. A multiple regression analysis revealed that the mFIM was associated with both the LT response (β=0.07 (0.01), p<0.001) and the PP response (β=0.07 (0.01), p<0.001) at admission. The false discovery rate log-worth values for LT and PP were 6.6 and 8.5, respectively. Our findings demonstrate that LT and PP scores at admission can help predict patients’ functional outcomes after an SCI, although the magnitude of their contributions is not high. No potential conflict of interest relevant to this article was reported.

AIP Publishing Acta Medica Okayama 0021-9606 160 9 2024 GenIce-core: Efficient algorithm for generation of hydrogen-disordered ice structures 094101 EN Masakazu Matsumoto Research Institute for Interdisciplinary Science, Okayama University Takuma Yagasaki Division of Chemical Engineering, Graduate School of Engineering Science, Osaka University Hideki Tanaka Toyota Physical and Chemical Research Institute Ice is different from ordinary crystals because it contains randomness, which means that statistical treatment based on ensemble averaging is essential. Ice structures are constrained by topological rules known as the ice rules, which give them unique anomalous properties. These properties become more apparent when the system size is large. For this reason, there is a need to produce a large number of sufficiently large crystals that are homogeneously random and satisfy the ice rules. We have developed an algorithm to quickly generate ice structures containing ions and defects. This algorithm is provided as an independent software module that can be incorporated into crystal structure generation software. By doing so, it becomes possible to simulate ice crystals on a previously impossible scale. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 19 2 2024 Japan-epiretinal membrane (J-ERM) registry: A prospective cohort study protocol investigating the surgical outcome of epiretinal membrane e0297347 EN Yuki Kanzaki Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Ishihara Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine Tetsuro Morita Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Muraoka Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine Shuhei Kimura Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Koto Kyorin Eye Center, Department of Ophthalmology, Kyorin University School of Medicine Ryo Kawasaki Division of Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine Takayuki Baba Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine Fumiki Okamoto Department of Ophthalmology, Graduate School of Medicine, Nippon Medical School Makoto Inoue Kyorin Eye Center, Department of Ophthalmology, Kyorin University School of Medicine Taiji Sakamoto Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences Akitaka Tsujikawa Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Epiretinal membrane (ERM) causes visual impairment such as reduction in visual acuity and metamorphopsia due to retinal traction. With the improvement of optical coherence tomography (OCT) and microincision vitrectomy surgery (MIVS), the surgery of ERM has significantly advanced. However, there have been no large-scale studies on the following: (1) how to evaluate visual impairment in ERM, (2) the relationship between OCT findings and visual function, (3) when is the optimal timing of surgery, and (4) the relationship between the surgical instruments as well as techniques and prognosis. The purpose of this study was to obtain evidence regarding these ERM surgeries. Methods and design This is a prospective, multicenter cohort study of ERM surgery in Japan from March 1, 2023, to March 31, 2027 (UMIN000048472, R-3468-2). Patients who underwent ERM surgery during the study period and agreed to participate in this study will be included. The goal is to have a total of 5,000 eyes surgically treated for ERM. The following data will be collected: age, gender, medical history, subjective symptoms, visual function before and 6 and 12 months after surgery, clinical findings, OCT data, surgical technique, instruments used in surgery, and complications. Discussion The results of this study will support the surgical decisions and procedures in ERM practices. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0028-0836 626 7999 2024 Oxygen-evolving photosystem II structures during S1–S2–S3 transitions 670 677 EN Hongjie Li Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Yoshiki Nakajima Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Eriko Nango Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Shigeki Owada Japan Synchrotron Radiation Research Institute Daichi Yamada Department of Picobiology, Graduate School of Life Science, University of Hyogo Kana Hashimoto Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Fangjia Luo Japan Synchrotron Radiation Research Institute Rie Tanaka RIKEN SPring-8 Center Fusamichi Akita Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Koji Kato Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Jungmin Kang RIKEN SPring-8 Center Yasunori Saitoh Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Shunpei Kishi Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Huaxin Yu Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Naoki Matsubara Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Hajime Fujii Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Michihiro Sugahara Japan Synchrotron Radiation Research Institute Mamoru Suzuki Institute for Protein Research, Osaka University Tetsuya Masuda Division of Food and Nutrition, Faculty of Agriculture, Ryukoku University Tetsunari Kimura Department of Chemistry, Graduate School of Science, Kobe University Tran Nguyen Thao Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Shinichiro Yonekura Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Long-Jiang Yu Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Takehiko Tosha RIKEN SPring-8 Center Kensuke Tono Japan Synchrotron Radiation Research Institute Yasumasa Joti Japan Synchrotron Radiation Research Institute Takaki Hatsui Japan Synchrotron Radiation Research Institute Makina Yabashi Japan Synchrotron Radiation Research Institute Minoru Kubo Department of Picobiology, Graduate School of Life Science, University of Hyogo So Iwata RIKEN SPring-8 Center Hiroshi Isobe Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Kizashi Yamaguchi Center for Quantum Information and Quantum Biology, Osaka University Michihiro Suga Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Jian-Ren Shen Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Photosystem II (PSII) catalyses the oxidation of water through a four-step cycle of Si states (i = 0–4) at the Mn4CaO5 cluster1,2,3, during which an extra oxygen (O6) is incorporated at the S3 state to form a possible dioxygen4,5,6,7. Structural changes of the metal cluster and its environment during the S-state transitions have been studied on the microsecond timescale. Here we use pump-probe serial femtosecond crystallography to reveal the structural dynamics of PSII from nanoseconds to milliseconds after illumination with one flash (1F) or two flashes (2F). YZ, a tyrosine residue that connects the reaction centre P680 and the Mn4CaO5 cluster, showed structural changes on a nanosecond timescale, as did its surrounding amino acid residues and water molecules, reflecting the fast transfer of electrons and protons after flash illumination. Notably, one water molecule emerged in the vicinity of Glu189 of the D1 subunit of PSII (D1-E189), and was bound to the Ca2+ ion on a sub-microsecond timescale after 2F illumination. This water molecule disappeared later with the concomitant increase of O6, suggesting that it is the origin of O6. We also observed concerted movements of water molecules in the O1, O4 and Cl-1 channels and their surrounding amino acid residues to complete the sequence of electron transfer, proton release and substrate water delivery. These results provide crucial insights into the structural dynamics of PSII during S-state transitions as well as O–O bond formation. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 18 11 2023 Association between oral condition and subjective psychological well-being among older adults attending a university hospital dental clinic: A cross-sectional study e0295078 EN Noriko Takeuchi Department of Preventive Dentistry, Okayama University Hospital Nanami Sawada Department of Preventive Dentistry, Okayama University Hospital Daisuke Ekuni Department of Preventive Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Manabu Morita Department of Oral Health, Takarazuka University of Medical and Health Care Positive psychological well-being has a favorable impact on survival rates in both healthy and unhealthy populations. Oral health is also associated with psychological well-being, is multidimensional in nature, and includes physical, psychological, emotional, and social domains that are integral to overall health and well-being. This study aimed to identify the associations between individual and environmental characteristics, oral condition and nutritional status in relation to subjective well-being among older adults using the Wilson and Cleary conceptual model. The participants were older adults (age >= 60 years) attending a university hospital. Subjective well-being was assessed using the World Health Organization-5 Well-Being Index, oral condition was assessed based on the number of bacteria in the tongue coating, oral wettability, tongue pressure, occlusal force, oral diadochokinesis, and masticatory ability, and subjective swallowing function was assessed using the Eating Assessment Tool, number of remaining teeth, and number of functional teeth. In addition, factors related to well-being, including social networks, life-space mobility, nutritional status, smoking history, drinking history, and medical history were assessed. In the analysis, structural equation modeling was used to investigate the association between oral condition and subjective well-being. Confirmatory factor analysis revealed oral condition as a latent variable, including tongue pressure, oral diadochokinesis /pa/, /ta/, /ka/, occlusal force, masticatory ability, subjective swallowing function, and number of functional teeth. Structural Equation Modeling revealed that oral condition was positively correlated with nutritional status, and nutritional status was positively correlated with the World Health Organization-5 Well-Being Index. These findings suggest that oral condition may influence subjective well-being via nutritional status or social environmental factors. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 3 2024 Inhibitory Effect of a Tankyrase Inhibitor on Mechanical Stress-Induced Protease Expression in Human Articular Chondrocytes 1443 EN Yoshifumi Hotta Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichiro Nishida Locomotive Pain Center, Okayama University Hospital Aki Yoshida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Nasu Department of Orthopaedic Surgery, Okayama University Hospital Ryuichi Nakahara Department of Orthopaedic Surgery, Okayama University Hospital Shuichi Naniwa Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriyuki Shimizu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chinatsu Ichikawa Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Deting Lin Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences We investigated the effects of a Tankyrase (TNKS-1/2) inhibitor on mechanical stress-induced gene expression in human chondrocytes and examined TNKS-1/2 expression in human osteoarthritis (OA) cartilage. Cells were seeded onto stretch chambers and incubated with or without a TNKS-1/2 inhibitor (XAV939) for 12 h. Uni-axial cyclic tensile strain (CTS) (0.5 Hz, 8% elongation, 30 min) was applied and the gene expression of type II collagen a1 chain (COL2A1), aggrecan (ACAN), SRY-box9 (SOX9), TNKS-1/2, a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), and matrix metalloproteinase-13 (MMP-13) were examined by real-time PCR. The expression of ADAMTS-5, MMP-13, nuclear translocation of nuclear factor-κB (NF-κB), and β-catenin were examined by immunocytochemistry and Western blotting. The concentration of IL-1β in the supernatant was examined by enzyme-linked immunosorbent assay (ELISA). TNKS-1/2 expression was assessed by immunohistochemistry in human OA cartilage obtained at the total knee arthroplasty. TNKS-1/2 expression was increased after CTS. The expression of anabolic factors were decreased by CTS, however, these declines were abrogated by XAV939. XAV939 suppressed the CTS-induced expression of catabolic factors, the release of IL-1β, as well as the nuclear translocation of NF-κB and β-catenin. TNKS-1/2 expression increased in mild and moderate OA cartilage. Our results demonstrated that XAV939 suppressed mechanical stress-induced expression of catabolic proteases by the inhibition of NF-κB and activation of β-catenin, indicating that TNKS-1/2 expression might be associated with OA pathogenesis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Long-Term Follow-up Data of a Multi-Institutional Phase-2 Study of S-1/oxaliplatin and Bevacizumab Therapy in Patients with Advanced Colorectal Cancer: The HiSCO-02 Study 47 52 EN Manabu Shimomura Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Katsunori Shinozaki Division of Clinical Oncology, Hiroshima Prefectural Hospital Takuya Yano Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Shintaro Akabane Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Hideki Ohdan Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Hiroshima Surgical study group of Clinical Oncology (HiSCO) Original Article 10.18926/AMO/66670 Oral fluoropyrimidines (FUs) have certain advantages over intravenous FUs, such as longer intervals between outpatient visits, no requirement for central venous port (CVP) implantation, and lower incidence of neutropenia. We previously reported the efficacy of S-1/oxaliplatin (SOX) with bevacizumab therapy as a first-line treatment for advanced colorectal cancer (CRC) in a prospective phase-II multi-institutional clinical trial (HiSCO-02 study). However, our prognostic data at the time lacked a sufficient observation period. Herein, we analyze the longer-term follow-up data, focusing on the status of eventual CVP implantation via an open-label, non-randomized, multicenter study. This study enrolled 55 patients (mean age, 64 years), of whom 43 died (41 of primary cancer). The median overall survival was 22.7 months (95% CI: 20.1-34.7 months). Post-treatment regimens after failure of first-line treatment were initiated in 43 patients; CPT11-based regimens were selected in most cases, and other oral FU combinations in nine. CVP was implanted in 35 patients prior to first-line treatment; eleven of the remaining 20 patients did not require CVP implantation. In conclusion, we report here the final prognostic update of the Phase II clinical trial examining the efficacy of SOX plus bevacizumab therapy, the results of which confirm the clinical efficacy of this regimen. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Regression of Necrotic Lesions after Methotrexate Withdrawal in Patients with Methotrexate-Associated Lymphoproliferative Disorders: A Retrospective CT Study 29 36 EN Takahiro Kitayama Department of Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Tanaka Department of Radiology, Okayama City Hospital Yuichiro Kanie Department of Radiology, Okayama University Hospital Yohei Marukawa Department of Radiology, Okayama Saiseikai General Hospital Katsuhide Kojima Department of Radiology, Okayama University Hospital Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soshi Takao Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takao Hiraki Department of Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Original Article 10.18926/AMO/66668 This retrospective study investigated whether necrotic lesions detected on a computed tomography (CT) scan are more regressive than non-necrotic lesions after methotrexate withdrawal in patients pathologically diagnosed with methotrexate-associated lymphoproliferative disorders (MTX-LPD). In total, 89 lesions extracted from 24 patients on CT scans were included in the analysis. All patients had been evaluated for the presence of necrosis within lesions via CT scan upon first suspicion of MTX-LPD (baseline CT scan). The percentage lesion size reduction between the baseline and initial follow-up CT scan was calculated. The association between necrosis within lesions and size changes was estimated via linear regression analyses using both crude and adjusted models. Necrosis was significantly more common in extranodal lesions (27 out of 30 lesions, 90%) than in nodal lesions (9 out of 59 lesions, 15%, p<0.001). In the crude model, the regression of necrotic lesions was 58.5% greater than that of non-necrotic lesions; the difference was statistically significant (p<0.001). Additionally, the longest diameter of necrotic lesions at the baseline CT scan was significantly greater than that of non-necrotic lesions (p<0.001). Based on the adjusted model, necrotic lesions showed 49.3% greater regression than non-necrotic lesions (p=0.017). Necrosis detected on a CT scan was found to be an independent predictor of regression after MTX withdrawal in patients with MTX-LPD. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9059 12 1 2024 Hydrogen in Transplantation: Potential Applications and Therapeutic Implications 118 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 Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takahiro Hirayama 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 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 Masaki Hisamura 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 Hydrogen gas, renowned for its antioxidant properties, has emerged as a novel therapeutic agent with applications across various medical domains, positioning it as a potential adjunct therapy in transplantation. Beyond its antioxidative properties, hydrogen also exerts anti-inflammatory effects by modulating pro-inflammatory cytokines and signaling pathways. Furthermore, hydrogen's capacity to activate cytoprotective pathways bolsters cellular resilience against stressors. In recent decades, significant advancements have been made in the critical medical procedure of transplantation. However, persistent challenges such as ischemia-reperfusion injury (IRI) and graft rejection continue to hinder transplant success rates. This comprehensive review explores the potential applications and therapeutic implications of hydrogen in transplantation, shedding light on its role in mitigating IRI, improving graft survival, and modulating immune responses. Through a meticulous analysis encompassing both preclinical and clinical studies, we aim to provide valuable insights into the promising utility of hydrogen as a complementary therapy in transplantation. No potential conflict of interest relevant to this article was reported.

岡山大学農学部 Acta Medica Okayama 2186-7755 113 2024 公表学術論文等リスト　2023 61 73 EN No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0003-4975 117 1 2024 Clinical Features of Patients With Second Primary Lung Cancer After Head and Neck Cancer 181 188 EN Fumiaki Takatsu Department of Thoracic Surgery, Okayama University Hospital Ken Suzawa Department of Thoracic Surgery, Okayama University Hospital Mikio Okazaki Department of Thoracic Surgery, Okayama University Hospital Kazuhiko Shien Department of Thoracic Surgery, Okayama University Hospital Hiromasa Yamamoto Department of Thoracic Surgery, Okayama University Hospital Mototsugu Watanabe Okayama University Thoracic Surgery Study Group Makio Hayama Okayama University Thoracic Surgery Study Group Tsuyoshi Ueno Okayama University Thoracic Surgery Study Group Ryujiro Sugimoto Okayama University Thoracic Surgery Study Group Yuho Maki Okayama University Thoracic Surgery Study Group Toshiya Fujiwara Okayama University Thoracic Surgery Study Group Riki Okita Okayama University Thoracic Surgery Study Group Hidetoshi Inokawa Okayama University Thoracic Surgery Study Group Hiroyuki Tao Okayama University Thoracic Surgery Study Group Yuji Hirami Okayama University Thoracic Surgery Study Group Eisuke Matsuda Okayama University Thoracic Surgery Study Group Kazuhiko Kataoka Okayama University Thoracic Surgery Study Group Motohiro Yamashita Okayama University Thoracic Surgery Study Group Yoshifumi Sano Okayama University Thoracic Surgery Study Group Motoki Matsuura Okayama University Thoracic Surgery Study Group Hisao Mizutani Okayama University Thoracic Surgery Study Group Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Background In survivors of head and neck cancer (HNC), second primary lung cancer (SPLC) often develop as a result of a common risk factor, that is, smoking. A multicenter experience was reviewed to evaluate how the history of a diagnosis of HNC affects the outcomes of patients undergoing pulmonary resection for SPLC. Methods A multicenter retrospective analysis of patients hospitalized between January 2012 and December 2018 was performed. From a cohort of 4521 patients undergoing therapeutic pulmonary resection for primary non-small cell lung cancer, 100 patients with a previous history of HNC (HNC group) were identified. These patients were compared with a control group consisting of 200 patients without an HNC history from the same cohort pair-matched with operating facility, age, sex, and pathologic stage of lung cancer. Results At the time of surgery for SPLC, the HNC group showed malnutrition with a lower prognostic nutritional index compared with the control group (P < .001). The HNC group was determined to have postoperative complications more frequently (P = .02). The 5-year overall survival rates in the HNC and control groups were 59.0% and 83.2%, respectively (P < .001). Statistically, HNC history, lower prognostic nutritional index, squamous cell lung cancer, and TNM stage were identified to be independently associated with poor survival. Conclusions Patients with SPLC after primary HNC often present with malnutrition and are predisposed to postoperative complications and poor survival after pulmonary resection. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2397-9070 8 1 2023 Clinical significance of gastrointestinal bleeding history in patients who undergo left atrial appendage closure e13009 EN Tatsuya Kikuchi Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiyasu Kono Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Nakagawa Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Okada Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masakazu Miyamoto Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoichi Takaya Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shoichiro Hirata Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shoko Inoo Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sakiko Kuraoka Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shotaro Okanoue Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Katsunori Matsueda Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuya Satomi Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenta Hamada Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaya Iwamuro Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Seiji Kawano Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background and Aim: Anticoagulant users with nonvalvular atrial fibrillation (NVAF) sometimes suffer from gastrointestinal bleeding (GIB) and have difficulty continuing the medication. Left atrial appendage closure (LAAC) has been developed for such situations. We aimed to clarify the clinical significance of a history of GIB in comparison to other factors in patients who had undergone LAAC. Methods: From October 2019 to September 2023, patients with NVAF who underwent LAAC at our hospital were enrolled. We investigated the percentage of patients with a history of GIB who underwent LAAC and compared the incidence of post-LAAC bleeding in these patients compared to those with other factors. Results: A total of 45 patients were included. There were 19 patients (42%) with a history of GIB who underwent LAAC. In a Kaplan–Meier analysis, the cumulative incidence of bleeding complications after LAAC was significantly higher in patients with a history of GIB in comparison to patients with other factors. There were eight cases of post-LAAC bleeding in total, and seven cases had GIB. Conclusions: We need to recognize that GIB is a significant complication in patients who undergo LAAC. The management of GIB by gastroenterologists is essential to the success of LAAC. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2666-9145 3 3 2023 Epiretinal Membrane Impairs the Inner Retinal Layer in a Traction Force-Dependent Manner 100312 EN Yuki Kanzaki Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryo Matoba Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shuhei Kimura Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mio M. Hosokawa Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Shiode Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinichiro Doi Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tetsuro Morita Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sayumi Kanzaki Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ippei Takasu Takasu Eye Clinic Atsuhiro Tanikawa Department of Ophthalmology, Fujita Health University Bantane Hospital Yuki Morizane Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose: To investigate the relationship between retinal traction force and impairment of the inner retinal layer in patients with epiretinal membrane (ERM). Design: Nonrandomized, retrospective consecutive case series. Participants: Two hundred nine eyes of 201 patients with idiopathic ERM who underwent vitrectomy for idiopathic ERM were enrolled. Methods: Retinal folds caused by ERM were visualized using en face OCT, and the maximum depth of retinal folds within the parafovea (MDRF) was measured. Focal macular electroretinogram (ERG) was used to measure the amplitude and implicit time of each component for the ERM eyes and the normal fellow eyes. B-scan OCT images were used to measure the thicknesses of the inner nuclear layer (INL) and outer nuclear layer (ONL) + outer plexiform layer (OPL). Expression of α-smooth muscle actin (α-SMA) in surgically removed ERM specimens was quantified by reverse-transcription polymerase chain reaction. Main Outcome Measures: We analyzed the relationship between MDRF and the relative amplitudes of focal macular ERG (affected eye/fellow eye), the relationships between MDRF and the mean INL thickness and ONL+OPL thickness, comparison of INL thickness and ONL+OPL thickness for each area when cases were classified according to MDRF localization in the ETDRS chart, and the relationship between MDRF and the relative expression of α-SMA in the ERM specimens. Results: The MDRF significantly correlated with the relative amplitudes (affected eye/fellow eye) of b-waves and oscillatory potentials (r = −0.657, P = 0.015; r = −0.569, P = 0.042, respectively) and the mean INL thickness and ONL+OPL thickness (r = 0.604, P < 0.001; r = 0.210, P = 0.007, respectively). However, only the INL thickness progression rate was significantly correlated with the MDRF progression rate (r = 0.770, P < 0.001). On case stratification by localization of MDRF based on the ETDRS chart, in regions other than temporal regions, the INL thickness was significantly greater in regions with MDRF than in other regions. The MDRF significantly correlated with α-SMA expression in the ERM specimens (r = 0.555, P = 0.009). Conclusions: The findings suggest that ERM impairs the inner retinal layer in a traction force-dependent manner. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1751-7311 17 7 2023 Effects of liquefied sake lees on growth performance and faecal and blood characteristics in Japanese Black calves 100873 EN S. Katsumata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Y. Hayashi Shiga Prefectural Livestock Production Technology Promotion Center K. Oishi Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University T. Tsukahara Kyoto Institute of Nutrition and Pathology R. Inoue Department of Applied Biological Sciences, Faculty of Agriculture, Setsunan University A. Obata Shiga Prefectural Livestock Production Technology Promotion Center H. Hirooka Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University H. Kumagai Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University Liquefied sake lees, a by-product of Japanese sake, is rich in Saccharomyces cerevisiae, proteins, and prebiotics derived from rice and yeast. Previous studies have reported that Saccharomyces cerevisiae fermentation products improved the health, growth, and faecal characteristics of preweaning calves. This study investigated the effects of adding liquefied sake lees to milk replacer on the growth performance, faecal characteristics, and blood metabolites of preweaning Japanese Black calves from 6 to 90 days of age. Twenty-four Japanese Black calves at 6 days of age were randomly assigned to one of three treatments: No liquefied sake lees (C, n = 8), 100 g/d (on a fresh matter basis) liquefied sake lees mixed with milk replacer (LS, n = 8), and 200 g/d (on a fresh matter basis) liquefied sake lees mixed with milk replacer (HS, n = 8). The intake of milk replacer and calf starter, as well as, the average daily gain did not differ between the treatments. The number of days counted with faecal score 1 in LS was higher than in HS (P < 0.05), while the number of days with diarrhoea medication in LS and C was lower than HS (P < 0.05). The faecal n-butyric acid concentration tended to be higher in LS compared to C (P = 0.060). The alpha diversity index (Chao1) was higher in HS than in C and LS at 90 days of age (P < 0.05). The principal coordinate analysis (PCoA) using weighted UniFrac distance showed that the bacterial community structures in faeces among the treatments at 90 days of age were significantly different (P < 0.05). The plasma β-hydroxybutyric acid concentration, an indicator of rumen development, was higher for LS than in C throughout the experiment (P < 0.05). These results suggested that adding liquefied sake lees up to 100 g/d (on a fresh matter basis) might promote rumen development in preweaning Japanese Black calves. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2079-7737 12 12 2023 Random Mutational Analysis Targeting Residue K155 within the Transmembrane β-Hairpin of the Mosquitocidal Mpp46Ab Toxin 1481 EN Midoka Miyazaki Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mami Asakura Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toru Ide Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tohru Hayakawa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mpp46Ab is a mosquito-larvicidal pore-forming toxin derived from Bacillus thuringiensis TK-E6. Pore formation is believed to be a central mode of Mpp46Ab action, and the cation selectivity of the channel pores, in particular, is closely related to its mosquito-larvicidal activity. In the present study, we constructed a mutant library in which residue K155 within the transmembrane β-hairpin was randomly replaced with other amino acid residues. Upon mutagenesis and following primary screening using Culex pipiens mosquito larvae, we obtained 15 mutants in addition to the wild-type toxin. Bioassays using purified proteins revealed that two mutants, K155E and K155I, exhibited toxicity significantly higher than that of the wild-type toxin. Although increased cation selectivity was previously reported for K155E channel pores, we demonstrated in the present study that the cation selectivity of K155I channel pores was also significantly increased. Considering the characteristics of the amino acids, the charge of residue 155 may not directly affect the cation selectivity of Mpp46Ab channel pores. Replacement of K155 with glutamic acid or isoleucine may induce a similar conformational change in the region associated with the ion selectivity of the Mpp46Ab channel pores. Mutagenesis targeting the transmembrane β-hairpin may be an effective strategy for enhancing the ion permeability of the channel pores and the resulting mosquito-larvicidal activity of Mpp46Ab. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Concomitant Use of Multiple Nephrotoxins including Renal Hypoperfusion Medications Causes Vancomycin-Associated Nephrotoxicity: Combined Retrospective Analyses of Two Real-World Databases 595 605 EN Takashi Bando Department of Pharmacy, Tokushima University Hospital Masayuki Chuma Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Hirofumi Hamano Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Takahiro Niimura Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Naoto Okada Department of Pharmacy, Tokushima University Hospital Masateru Kondo Department of Pharmacy, Tokushima University Hospital Yuki Izumi Department of Pharmacy, Tokushima University Hospital Shunsuke Ishida Department of Pharmacy, Tokushima University Hospital Toshihiko Yoshioka Department of Pharmacy, Tokushima University Hospital Mizuho Asada Department of Medical Molecular Informatics, Meiji Pharmaceutical University Yoshito Zamami Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Kenshi Takechi Department of Drug Information Analysis, College of Pharmaceutical Sciences, Matsuyama University Mitsuhiro Goda Department of Pharmacy, Tokushima University Hospital Koji Miyata Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Kenta Yagi Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Yuki Izawa-Ishizawa Department of Pharmacology, Tokushima University Graduate School of Biomedical Sciences Momoyo Azuma Department of Infection Control and Prevention, Tokushima University Hospital Hiroaki Yanagawa Department of Nursing, Faculty of Health and Welfare, Tokushima Bunri University Yoshikazu Tasaki Department of Hospital Pharmacy and Pharmacology, Asahikawa Medical University Keisuke Ishizawa Department of Pharmacy, Tokushima University Hospital Original Article 10.18926/AMO/66151 There is a growing concern about the relationship between vancomycin-associated nephrotoxicity (VAN) and concomitant use of nephrotoxins. We examined this relationship by combined retrospective analyses of two real-world databases. Initially, the FDA Adverse Event Reporting System (FAERS) was analyzed for the effects of concomitant use of one or more nephrotoxins on VAN and the types of combinations of nephrotoxins that exacerbate VAN. Next, electronic medical records (EMRs) of patients who received vancomycin (VCM) at Tokushima University Hospital between January 2006 and March 2019 were examined to confirm the FAERS analysis. An elevated reporting odds ratio (ROR) was observed with increases in the number of nephrotoxins administered (VCM + one nephrotoxin, adjusted ROR (95% confidence interval [CI]) 1.67 [1.51-1.85]; VCM + ≥2 nephrotoxins, adjusted ROR [95% CI] 1.54 [1.37-1.73]) in FAERS. EMRs analysis showed that the number of nephrotoxins was associated with higher incidences of VAN [odds ratio: 1.99; 95% CI: 1.42-2.78]. Overall, concomitant use of nephrotoxins was associated with an increased incidence of VAN, especially when at least one of those nephrotoxins was a renal hypoperfusion medication (furosemide, non-steroidal anti-inflammatory drugs, and vasopressors). The concomitant use of multiple nephrotoxins, especially including renal hypoperfusion medication, should be avoided to prevent VAN. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 SHRSP5/Dmcr rats fed a high-fat and high-cholesterol diet develop disease-induced sarcopenia as nonalcoholic steatohepatitis progresses EN Shusei YAMAMOTO Graduate School of Health Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Development of novel probe for detecting two mutations on one RNA EN MYAT THU Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Application of amorphous sugar matrix dried from alcohol to solid dispersion of hydrophobic drug and its physicochemical characteristics EN Koji TAKEDA Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Pacsin 2-dependent N-cadherin internalization regulates the migration behaviour of malignant cancer cells EN HAYMAR WINT Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

AIP Publishing Acta Medica Okayama 1932-1058 17 5 2023 Diamond quantum sensors in microfluidics technology 054107 EN Masazumi Fujiwara Department of Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Diamond quantum sensing is an emerging technology for probing multiple physico-chemical parameters in the nano- to micro-scale dimensions within diverse chemical and biological contexts. Integrating these sensors into microfluidic devices enables the precise quantification and analysis of small sample volumes in microscale channels. In this Perspective, we present recent advancements in the integration of diamond quantum sensors with microfluidic devices and explore their prospects with a focus on forthcoming technological developments. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 1664-3224 14 2023 “Input/output cytokines” in epidermal keratinocytes and the involvement in inflammatory skin diseases 1239598 EN Shin Morizane Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Mukai Department of Immunology and Molecular Genetics, Kawasaki Medical School Ko Sunagawa Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kota Tachibana Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshio Kawakami Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mamoru Ouchida Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Considering the role of epidermal keratinocytes, they occupy more than 90% of the epidermis, form a physical barrier, and also function as innate immune barrier. For example, epidermal keratinocytes are capable of recognizing various cytokines and pathogen-associated molecular pattern, and producing a wide variety of inflammatory cytokines, chemokines, and antimicrobial peptides. Previous basic studies have shown that the immune response of epidermal keratinocytes has a significant impact on inflammatory skin diseases. The purpose of this review is to provide foundation of knowledge on the cytokines which are recognized or produced by epidermal keratinocytes. Since a number of biologics for skin diseases have appeared, it is necessary to fully understand the relationship between epidermal keratinocytes and the cytokines. In this review, the cytokines recognized by epidermal keratinocytes are specifically introduced as "input cytokines", and the produced cytokines as "output cytokines". Furthermore, we also refer to the existence of biologics against those input and output cytokines, and the target skin diseases. These use results demonstrate how important targeted cytokines are in real skin diseases, and enhance our understanding of the cytokines. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 1664-462X 14 2023 FZL, a dynamin-like protein localized to curved grana edges, is required for efficient photosynthetic electron transfer in Arabidopsis 1279699 EN Yu Ogawa Institute of Plant Science and Resources, Okayama University Megumi Iwano Graduate School of Biostudies, Kyoto University Toshiharu Shikanai Department of Botany, Graduate School of Science, Kyoto University Wataru Sakamoto Institute of Plant Science and Resources, Okayama University Photosynthetic electron transfer and its regulation processes take place on thylakoid membranes, and the thylakoid of vascular plants exhibits particularly intricate structure consisting of stacked grana and flat stroma lamellae. It is known that several membrane remodeling proteins contribute to maintain the thylakoid structure, and one putative example is FUZZY ONION LIKE (FZL). In this study, we re-evaluated the controversial function of FZL in thylakoid membrane remodeling and in photosynthesis. We investigated the sub-membrane localization of FZL and found that it is enriched on curved grana edges of thylakoid membranes, consistent with the previously proposed model that FZL mediates fusion of grana and stroma lamellae at the interfaces. The mature fzl thylakoid morphology characterized with the staggered and less connected grana seems to agree with this model as well. In the photosynthetic analysis, the fzl knockout mutants in Arabidopsis displayed reduced electron flow, likely resulting in higher oxidative levels of Photosystem I (PSI) and smaller proton motive force (pmf). However, nonphotochemical quenching (NPQ) of chlorophyll fluorescence was excessively enhanced considering the pmf levels in fzl, and we found that introducing kea3-1 mutation, lowering pH in thylakoid lumen, synergistically reinforced the photosynthetic disorder in the fzl mutant background. We also showed that state transitions normally occurred in fzl, and that they were not involved in the photosynthetic disorders in fzl. We discuss the possible mechanisms by which the altered thylakoid morphology in fzl leads to the photosynthetic modifications. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Favorable Outcome of Repeated Salvage Surgeries for Rare Metastasis to the Ligamentum Teres Hepatis and the Upper Abdominal Wall in a Stage IV Gastric Cancer Patient 553 559 EN Takahiro Murokawa Department of Gastroenterological Surgery, Kochi Health Sciences Center Shinya Sakamoto Department of Gastroenterological Surgery, Kochi Health Sciences Center Motoyasu Tabuchi Department of Gastroenterological Surgery, Kochi Health Sciences Center Kenta Sui Department of Gastroenterological Surgery, Kochi Health Sciences Center Kazuhide Ozaki Department of Gastroenterological Surgery, Kochi Health Sciences Center Manabu Matsumoto Department of Diagnostic Pathology, Kochi Health Sciences Center Jun Iwata Department of Diagnostic Pathology, Kochi Health Sciences Center Takehiro Okabayashi Department of Gastroenterological Surgery, Kochi Health Sciences Center Hiroshi Yoshida Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School Case Report 10.18926/AMO/65979 Gastric cancer with peritoneal metastases is typically a devastating diagnosis. Ligamentum teres hepatis (LTH) metastasis is an extremely rare presentation with only four known cases. Herein, we report salvage surgery of successive metastases to the abdominal wall and LTH in a patient originally presenting with advanced gastric cancer with peritoneal metastasis, leading to long-term survival. A 72-year-old man with advanced gastric cancer underwent curative-intent distal gastrectomy with D2 lymph node dissection for gastric outlet obstruction. During this procedure, three small peritoneal metastases were detected in the lesser omentum, the small mesentery, and the mesocolon; however, intraoperative abdominal lavage cytology was negative. We added cytoreductive surgery for peritoneal metastasis. The pathological diagnosis of the gastric cancer was tubular adenocarcinoma with pT4aN1pM1(PER/P1b)CY0 stage IV (Japanese classification of gastric carcinoma/JCGC 15th), or T4N1M1b stage IV (UICC 7th). Post-operative adjuvant chemotherapy with S-1 (TS-1)+cisplatin (CDDP) was administered for 8 months followed by S-1 monotherapy for 4 months. At 28 months after the initial surgery, a follow-up computed tomography (CT) detected a small mass beneath the upper abdominal wall. The ass showed mild avidity on 18F-fluorodeoxyglucose positron-emission (FDG-PET) CT. Salvage resection was performed for diagnosis and treatment, and pathological findings were consistent with primary gastric cancer metastasis. At 49 months after the initial gastrectomy, a new lesion was detected in the LTH with a similar level of avidity on FDG-PET CT as the abdominal wall metastatic lesion. We performed a second salvage surgery for the LTH tumor, which also showed pathology of gastric cancer metastasis. There has been no recurrence up to 1 year after the LTH surgery. With multidisciplinary treatment the patient has survived almost 5 years after the initial gastrectomy. Curative-intent gastrectomy with cytoreductive surgery followed by adjuvant chemotherapy for advanced gastric cancer with localized peritoneal metastasis might have had a survival benefit in our patient. Successive salvage surgeries for oligometastatic lesions in the abdominal wall and the LTH also yielded favorable outcomes. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Associations among Preoperative Malnutrition, Muscle Loss, and Postoperative Walking Ability in Intertrochanteric Fractures: A Retrospective Study 511 516 EN Kohei Sato Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hironori Tsuji Department of Orthopedic Surgery, Japanese Red Cross Okayama Hospital Masanori Yorimitsu Department of Orthopedic Surgery, Okayama University Hospital Takenori Uehara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Okazaki Department of Orthopedic Surgery, Tsuyama Chuo Hospital Shinichiro Takao Department of Orthopedic Surgery, Okayama Medical Center Toshiaki Hata Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shiro Fukuoka Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Noda Department of Orthopedic Surgery, Kawasaki Medical School, General Medical Center Hideyuki Kanda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65973 Sarcopenia and malnutrition are increasing in older adults and are reported risk factors for functional impairment after hip fracture surgery. This study aimed to investigate the associations between skeletal muscle mass loss, malnutrition, and postoperative walking ability in patients with hip fracture. We retrospectively reviewed patients who underwent intertrochanteric fracture surgery at our institute. The psoas muscle index, controlling nutritional status score, and functional ambulation category (FAC) were used to evaluate skeletal muscle mass, nutritional status, and walking ability, respectively. Six months after surgery, walking ability was assessed as either “gait disturbance” or “independent gait”. Multivariate binomial logistic regression analysis, with skeletal muscle mass, nutritional status, and other factors, was used to predict the risk of being assigned to the gait disturbance group. This study included 95 patients (mean age, 85.2 years; 70 women). Sixty-six patients had low skeletal muscle mass, 35 suffered from malnutrition, and 28 had both. Malnutrition and low skeletal muscle mass were significantly associated with postoperative gait disturbance (FAC < 3). Preoperative low skeletal muscle mass and malnutrition were risk factors for postoperative poor walking ability. Further preventive interventions focusing on skeletal muscle mass and nutritional status are required. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Relationship between the Hip Abductor Muscles and Abduction Strength in Patients with Hip Osteoarthritis 461 469 EN Daisuke Homma Division of Orthopaedic Surgery, Niigata University Graduate School of Medical and Dental Sciences Izumi Minato Division of Orthopaedic Surgery, Niigata Rinko Hospital Norio Imai Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences Dai Miyasaka Division of Orthopaedic Surgery, Niigata Bandai Hospital Yoshinori Sakai Division of Orthopaedic Surgery, Niigata City General Hospital Yoji Horigome Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences Hayato Suzuki Division of Orthopaedic Surgery, Niigata University Graduate School of Medical and Dental Sciences Yoichiro Dohmae Division of Orthopaedic Surgery, Niigata Bandai Hospital Naoto Endo Division of Orthopaedic Surgery, Niigata Prefectural Tsubame Rosai Hospital Original Article 10.18926/AMO/65968 This study aimed to determine which muscle the gluteus maximus, gluteus medius, gluteus minimus (Gmin), or tensor fasciae latae (TFL) contributes most to hip abduction strength and to identify effective sites for cross-sectional area (CSA) Gmin and TFL measurement in hip osteoarthritis (OAhip) patients. Twenty-eight patients with OAhip were included. The muscle CSA and volume were determined using magnetic resonance imaging. Peak isometric strength was determined using hand-held dynamometry. Muscle volumes were normalized to the total muscle volume of hip abductors. Multiple regression analysis was performed. The difference between the CSA of Gmin and TFL was calculated, and correlations with volume and muscle strength were determined. Gmin volume was related to abductor muscle strength (p=0.042). The peak CSA of the Gmin correlated with muscle volume and strength. The CSA of the TFL correlated with volume, with no difference between the CSA of the most protruding part of the lesser trochanter and peak CSA. Gmin volume was strongly related to abductor muscle strength. Peak CSA is a useful parameter for assessing the CSA of the Gmin among patients with OAhip. The CSA of the TFL should be measured at the most protruding part of the lesser trochanter. No potential conflict of interest relevant to this article was reported.

Fuji Technology Press Ltd. Acta Medica Okayama 1883-8049 34 2 2022 Development of a Spiral Shaped Soft Holding Actuator Using Extension Type Flexible Pneumatic Actuators 373 381 EN So Shimooka Graduate School of Natural Science and Technology, Okayama University Tetsuya Akagi Department of Intelligent Mechanical Engineering, Okayama University of Science Shujiro Dohta Department of Intelligent Mechanical Engineering, Okayama University of Science Takashi Shinohara Design and Manufacturing Center, Organization for Research Development and Outreach, Okayama University of Science Takumi Kobayashi Department of Intelligent Mechanical Engineering, Okayama University of Science Recently, several pneumatic soft actuators have been applied to wearable and welfare devices to provide nursing care and physical support for the elderly and disabled. In this study, as a wearable soft actuator for holding body, a spiral shaped soft holding actuator that can wrap a user according to their body shape was proposed and tested. The construction and operating principle of the tested soft actuator with circumferential restraint mechanism using three extension type flexible pneumatic actuators (EFPAs) has been discussed. As a result, it was found that the tested actuator could hold elbows and knees when the joint is in motion. An analytical model of the spiral actuator was also proposed to achieve an optimal design. It can be confirmed that the proposed analytical model can predict the shape of the actuator when various EFPAs are pressurized. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 2770-5781 81 1 2022 Improvement of anterior disc displacement on the mandibular deviated side after intraoral vertical ramus osteotomy in a patient with facial asymmetry: a case report 58 67 EN Hirotaka Ueda Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoki Oka Department of Orthodontics, Okayama University Hospital Tsuyoshi Shimo Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido Akira Sasaki Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Yamashiro Department of Orthodontics and Dentofacial Orthopedics, Osaka University Graduate School of Dentistry Hiroshi Kamioka Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose: We present the orthognathic treatment of an adult skeletal Class III patient with facial asymmetry, mandibular rightward deviation, and anterior disc displacement without reduction (ADDwoR) at the right temporomandibular joint (TMJ) by intraoral vertical ramus osteotomy (IVRO). Materials and methods: The patient was a 23-year-old man with complaints of mandibular deviation and crowded lower anterior teeth, resulting in facial asymmetry. The maxillary position was normal with protrusion and rightward deviation of the mandible. There was no cant of the maxilla. He experienced pain in the right TMJ during mastication, and Magnetic resonance imaging (MRI) revealed an ADDwoR on the right side. The patient was diagnosed with Class III malocclusion, skeletal Class III prognathism with mandibular deviation, and ADDwoR on the right side. Orthognathic surgery was proposed for jaw deformity, and IVRO was performed to correct mandibular deviation. Results: One year and 2 months after treatment onset, IVRO was performed with differential setback: 2 mm on the right and 8 mm on the left side of the mandible. The midline of the lower dentition was rotated by 6 mm to coincide with the facial midline. Symptoms of temporomandibular disorders were not observed post-operatively. Active-treatment period was for 31 months. MRI findings showed improvement in anterior disc displacement on the right side during the post-retention. Conclusion: In the case of facial asymmetry with anterior disc displacement on the mandibular deviated side, IVRO was suggested to have a potential effect on the positional relationship between the mandibular head and temporomandibular disc. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 An Unusual Presentation of Chest Pain and Laryngeal Discomfort in a Pregnant Woman: A Case Report and Literature Review 429 431 EN Misa Sasanami Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuyoshi Iida Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaya Iwamuro Department of Gastroenterology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryousuke Hirai Department of Gastroenterology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Obara Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Tsukahara 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 Atsunori Nakao Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/65755 Intramural esophageal dissection (IED), characterized by bleeding into the submucosal space, leads to mucosal separation and dissection. The most prevalent symptoms are sudden chest or retrosternal pain, hematemesis, and dysphagia. Therefore, acute coronary syndrome and aortic dissection are among its most notable differential diagnoses. A 31-year-old pregnant woman presented with acute chest pain, laryngeal discomfort, and hematemesis. Emergency esophagogastroscopy revealed longitudinal mucosal dissection (upper esophagus to esophagogastric junction). The patient was successfully treated by avoiding the ingestion of solid foods. Clinicians should consider a diagnosis of IED for pregnant patients with acute chest pain, especially if hematemesis is present. No potential conflict of interest relevant to this article was reported.

Japan Atherosclerosis Society Acta Medica Okayama 1340-3478 30 12 2023 Enhanced Production of EPA-Derived Anti-Inflammatory Metabolites after Oral Administration of a Novel Self-Emulsifying Highly Purified EPA Ethyl Ester Formulation (MND-2119) 1927 1949 EN Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoko Naoe Medical Affairs Department, Mochida Pharmaceutical Co., Ltd. Hiroyuki Wakabayashi Medical Affairs Department, Mochida Pharmaceutical Co., Ltd. Takashi Yano Medical Affairs Department, Mochida Pharmaceutical Co., Ltd. Takuya Mori Clinical Research Department, Mochida Pharmaceutical Co., Ltd. Shingo Kanda Clinical Development Planning and Management Department, Mochida Pharmaceutical Co., Ltd. Makoto Arita Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aims: MND-2119 is a novel once-daily dose self-emulsifying formulation of highly purified eicosapentaenoic acid ethyl ester (EPA-E) and is approved as an antihyperlipidemia agent in Japan. It has improved absorption and achieves higher plasma EPA concentrations at Cmax than conventional EPA-E. In the JELIS trial, concomitant use of EPA-E with statin therapy significantly reduced atherosclerotic cardiovascular disease (ASCVD) risks. As a potential mechanism of action of EPA, endogenous formation of EPA-derived anti-inflammatory metabolites is receiving greater attention. This study aims to investigate the endogenous formation of EPA-derived anti-inflammatory metabolites following single and multiple administrations of MND-2119. Methods: Healthy adult male subjects were randomly assigned to a nonintervention (control) group, MND-2119 2-g/day group, MND-2119 4-g/day group, or EPA-E 1.8-g/day group for 7 days (N=8 per group). Plasma fatty acids and EPA-derived metabolites were evaluated. Peripheral blood neutrophils were isolated, and the production of EPA-derived metabolites from in vitro stimulated neutrophils was evaluated. Results: After single and multiple administrations of MND-2119 2 g/day, there were significant increases in plasma EPA concentration, 18-hydroxyeicosapentaenoic acid (18-HEPE), and 17,18-epoxyeicosatetraenoic acid compared with those of EPA-E 1.8 g/day. They were further increased with MND-2119 4 g/day administration. In neutrophils, the EPA concentration in the MND-2119 2-g/day group was significantly higher compared with that in the EPA-E 1.8-g/day group after multiple administration, and 18-HEPE production was positively correlated with EPA concentration. No safety issues were noted. Conclusions: These results demonstrate that MND-2119 increases the plasma and cellular concentrations of EPA and EPA-derived metabolites to a greater extent than conventional EPA-E formulations. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 13 1 2023 Effectiveness of deep learning classifiers in histopathological diagnosis of oral squamous cell carcinoma by pathologists 11676 EN Shintaro Sukegawa Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sawako Ono Department of Pathology, Kagawa Prefectural Central Hospital Futa Tanaka Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University Yuta Inoue Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University Takeshi Hara Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University Kazumasa Yoshii Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kiyofumi Takabatake Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shimada Katsumitsu Department of Oral Pathology, Graduate School of Oral Medicine, Matsumoto Dental University Fumi Nakai Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine Yasuhiro Nakai Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine Ryo Miyazaki Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine Satoshi Murakami Department of Oral Pathology, Graduate School of Oral Medicine, Matsumoto Dental University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Minoru Miyake Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine The study aims to identify histological classifiers from histopathological images of oral squamous cell carcinoma using convolutional neural network (CNN) deep learning models and shows how the results can improve diagnosis. Histopathological samples of oral squamous cell carcinoma were prepared by oral pathologists. Images were divided into tiles on a virtual slide, and labels (squamous cell carcinoma, normal, and others) were applied. VGG16 and ResNet50 with the optimizers stochastic gradient descent with momentum and spectral angle mapper (SAM) were used, with and without a learning rate scheduler. The conditions for achieving good CNN performances were identified by examining performance metrics. We used ROCAUC to statistically evaluate diagnostic performance improvement of six oral pathologists using the results from the selected CNN model for assisted diagnosis. VGG16 with SAM showed the best performance, with accuracy = 0.8622 and AUC = 0.9602. The diagnostic performances of the oral pathologists statistically significantly improved when the diagnostic results of the deep learning model were used as supplementary diagnoses (p-value = 0.031). By considering the learning results of deep learning model classifiers, the diagnostic accuracy of pathologists can be improved. This study contributes to the application of highly reliable deep learning models for oral pathological diagnosis. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2041-1723 14 1 2023 Pivotal role for S-nitrosylation of DNA methyltransferase 3B in epigenetic regulation of tumorigenesis 621 EN Kosaku Okuda Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kengo Nakahara Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Akihiro Ito Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science Yuta Iijima 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 Ashutosh Kumar Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN Kana Fujikawa Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kazuya Adachi Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yuki Shimada Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Satoshi Fujio Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Reina Yamamoto 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 Kunishige Onuma Division of Experimental Pathology, Faculty of Medicine, Tottori University Mitsuhiko Osaki Division of Experimental Pathology, Faculty of Medicine, Tottori University Futoshi Okada Division of Experimental Pathology, Faculty of Medicine, Tottori University Taichi Ukegawa Department of Synthetic and Medicinal Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yasuo Takeuchi Department of Synthetic and Medicinal Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Norihisa Yasui Laboratory of Structural Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsuko Yamashita Laboratory of Structural Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiroyuki Marusawa Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University Yosuke Matsushita Division of Genome Medicine, Institute of Advanced Medical Sciences, Tokushima University Toyomasa Katagiri Division of Genome Medicine, Institute of Advanced Medical Sciences, Tokushima University Takahiro Shibata Graduate School of Bioagricultural Sciences, Nagoya University Koji Uchida Laboratory of Food Chemistry, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo Sheng-Yong Niu Broad Institute of MIT and Harvard Nhi B. Lang Neurodegeneration New Medicines Center, and Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute Tomohiro Nakamura Neurodegeneration New Medicines Center, and Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute Kam Y. J. Zhang Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN Stuart A. Lipton Neurodegeneration New Medicines Center, and Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute Takashi Uehara Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University DNA methyltransferases (DNMTs) catalyze methylation at the C5 position of cytosine with S-adenosyl-l-methionine. Methylation regulates gene expression, serving a variety of physiological and pathophysiological roles. The chemical mechanisms regulating DNMT enzymatic activity, however, are not fully elucidated. Here, we show that protein S-nitrosylation of a cysteine residue in DNMT3B attenuates DNMT3B enzymatic activity and consequent aberrant upregulation of gene expression. These genes include Cyclin D2 (Ccnd2), which is required for neoplastic cell proliferation in some tumor types. In cell-based and in vivo cancer models, only DNMT3B enzymatic activity, and not DNMT1 or DNMT3A, affects Ccnd2 expression. Using structure-based virtual screening, we discovered chemical compounds that specifically inhibit S-nitrosylation without directly affecting DNMT3B enzymatic activity. The lead compound, designated DBIC, inhibits S-nitrosylation of DNMT3B at low concentrations (IC50 <= 100nM). Treatment with DBIC prevents nitric oxide (NO)-induced conversion of human colonic adenoma to adenocarcinoma in vitro. Additionally, in vivo treatment with DBIC strongly attenuates tumor development in a mouse model of carcinogenesis triggered by inflammation-induced generation of NO. Our results demonstrate that de novo DNA methylation mediated by DNMT3B is regulated by NO, and DBIC protects against tumor formation by preventing aberrant S-nitrosylation of DNMT3B. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 9 1 2023 Adenocarcinoma arising from widespread heterotopic gastric mucosa in the cervicothoracic esophagus: a case report 132 EN Shohei Nogi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Kato Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Shirakawa Department of Surgery, Hiroshima City Hiroshima Citizens Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background　In Japan, about 6% of esophageal cancers are adenocarcinomas, although most of them arise from Barrett's epithelium. Adenocarcinoma arising from heterotopic gastric mucosa (HGM) is very rare. Due to its rarity, there is no unified view on its treatment strategy and prognosis. Case presentation　A 57-year-old man presented with a protruding lesion in the cervicothoracic esophagus that was detected by an upper gastrointestinal series at a medical checkup. Esophagoscopy revealed a 30 mm Type 1 tumor circumferentially surrounded by widespread HGM. Computed tomography (CT) and fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT showed no metastasis or invasion of the surrounding organs. We diagnosed the lesion as cT2N0M0 cStageIIB [Union for International Cancer Control (UICC) 8th Ed] cancer and performed subtotal esophagectomy with three-field lymph node dissection. The tumor was determined to be a well-differentiated adenocarcinoma arising from HGM, with deep invasion of the submucosa. The patient underwent no adjuvant therapy and has currently survived without any evidence of recurrence for 15 months. Conclusions　Although the treatment for adenocarcinoma arising from HGM is basically the same as that for squamous cell carcinoma (SCC) of the esophagus, it is important to determine the treatment strategy based on the characteristics of the adenocarcinoma arising from HGM. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6643 15 13 2023 Adrenomedullin Enhances Mouse Gustatory Nerve Responses to Sugars via T1R-Independent Sweet Taste Pathway 2941 EN Shusuke Iwata Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University Ryusuke Yoshida Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shingo Takai Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University Keisuke Sanematsu Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University Noriatsu Shigemura Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University Yuzo Ninomiya Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University On the tongue, the T1R-independent pathway (comprising glucose transporters, including sodium-glucose cotransporter (SGLT1) and the K-ATP channel) detects only sugars, whereas the T1R-dependent (T1R2/T1R3) pathway can broadly sense various sweeteners. Cephalic-phase insulin release, a rapid release of insulin induced by sensory signals in the head after food-related stimuli, reportedly depends on the T1R-independent pathway, and the competitive sweet taste modulators leptin and endocannabinoids may function on these two different sweet taste pathways independently, suggesting independent roles of two oral sugar-detecting pathways in food intake. Here, we examined the effect of adrenomedullin (ADM), a multifunctional regulatory peptide, on sugar sensing in mice since it affects the expression of SGLT1 in rat enterocytes. We found that ADM receptor components were expressed in T1R3-positive taste cells. Analyses of chorda tympani (CT) nerve responses revealed that ADM enhanced responses to sugars but not to artificial sweeteners and other tastants. Moreover, ADM increased the apical uptake of a fluorescent D-glucose derivative into taste cells and SGLT1 mRNA expression in taste buds. These results suggest that the T1R-independent sweet taste pathway in mouse taste cells is a peripheral target of ADM, and the specific enhancement of gustatory nerve responses to sugars by ADM may contribute to caloric sensing and food intake. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0902-0063 37 11 2023 Percentage of low attenuation area on computed tomography detects chronic lung allograft dysfunction, especially bronchiolitis obliterans syndrome, after bilateral lung transplantation e15077 EN Yujiro Kubo 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 Toshio Shiotani Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Kei Matsubara Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Kohei Hashimoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Shin Tanaka Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Kazuhiko Shien Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Ken Suzawa Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Kentaroh Miyoshi Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Hiromasa Yamamoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Mikio Okazaki Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Introduction: The percentage of low attenuation area (%LAA) on computed tomography (CT) is useful for evaluating lung emphysema, and higher %LAA was observed in patients with chronic lung allograft dysfunction (CLAD). This study investigated the relationship between the %LAA and the development of CLAD after bilateral lung transplantation (LT). Methods: We conducted a single-center retrospective study of 75 recipients who underwent bilateral LT; the recipients were divided into a CLAD group (n = 30) and a non-CLAD group (n = 45). The %LAA was calculated using CT and compared between the two groups from 4 years before to 4 years after the diagnosis of CLAD. The relationships between the %LAA and the percent baseline values of the pulmonary function test parameters were also calculated. Results: The %LAA was significantly higher in the CLAD group than in the non-CLAD group from 2 years before to 2 years after the diagnosis of CLAD (P < .05). In particular, patients with bronchiolitis obliterans syndrome (BOS) exhibited significant differences even from 4 years before to 4 years after diagnosis (P < .05). Significant negative correlations between the %LAA and the percent baseline values of the forced expiratory volume in 1 s (r = −.36, P = .0031), the forced vital capacity (r = −.27, P = .027), and the total lung capacity (r = −.40, P < .001) were seen at the time of CLAD diagnosis. Conclusion: The %LAA on CT was associated with the development of CLAD and appears to have the potential to predict CLAD, especially BOS, after bilateral LT. No potential conflict of interest relevant to this article was reported.

MYU K.K. Acta Medica Okayama 0914-4935 34 8 2022 A Method for Estimating Physician Stress Using Wearable Sensor Devices 2955 2971 EN Issei Imura Graduate School of Natural Science and Technology, Okayama University Yusuke Gotoh Faculty of Natural Science and Technology, Okayama University Koji Sakai Department of Radiology, Kyoto Prefectural University of Medicine Yu Ohara Department of Radiology, Kyoto Prefectural University of Medicine Jun Tazoe Department of Radiology, Kyoto Prefectural University of Medicine Hiroshi Miura Department of Radiology, Kyoto Prefectural University of Medicine Tatsuya Hirota Department of Radiology, Kyoto Prefectural University of Medicine Akira Uchiyama Graduate School of Information Science and Technology, Osaka University Yoshinari Nomura Faculty of Natural Science and Technology, Okayama University The idea of Society 5.0 initiative has been proposed to solve various social problems by connecting virtual cyberspace and real physical space through information technology. When applying the idea to improve the work-life balance of physicians in the medical field, we must consider the increased stress owing to their long continuous working hours. Estimating the stress of physicians in their daily lives by the questionnaires is insufficient, because of the difficulty of accurate their activity recalling. By using bio-metric information such as heart rate, physical activity, and sleeping information, it was expected that the daily stress state of physicians with high accuracy. In this paper, we propose a method for estimating physician stress by analyzing bio-metric information acquired by wearing a wearable sensor device. The proposed method estimates the state of stress during daily activities by acquiring data on heart rate variability (HRV) during wakefulness as well as sleep depth during rapid eye movement (REM) and non-REM sleep. Up to seven physicians wore the wearable sensor device for the maximum of eight weeks and the sleep depth and low-/high-frequency (LF/HF) components of HRV were obtained. Our observation showed that physicians' root mean square of successive differences (rMSSDs) were constantly high in their healthy state. Therefore, the decreasing of this index can be used as an indicator of fatigue and stress. In addition, by combining LF/HF components to the rMSSDs, we may estimate the stress state of physicians and find personal stressors. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2470-1343 8 12 2023 Development of Pipetteless Paper-Based Analytical Devices with a Volume Gauge 11213 11219 EN Kaewta Danchana Department of Chemistry, Okayama University Hiroshi Iwasaki Department of Chemistry, Okayama University Yada Thayawutthikun Flow Innovation-Research for Science and Technology Laboratories (FIRST Labs), Mahidol University Phoonthawee Saetear Flow Innovation-Research for Science and Technology Laboratories (FIRST Labs), Mahidol University Takashi Kaneta Department of Chemistry, Okayama University In this work, we propose a new design for paper based analytical devices (PADs) that eliminate the need to use a micropipette for sample introduction. With this design, a PAD is equipped with a distance-based detection channel that is connected to a storage channel that indicates the volume of a sample introduced into the PAD. The analyte in the sample solution reacts with a colorimetric reagent deposited into the distance-based detection channel as the sample solution flows into the storage channel where the volume is measured. The ratio of the lengths of the detection channel and that of the storage channel (D/S ratio) are constant for a sample containing a certain concentration, which is independent of the introduced volume. Therefore, the PADs permit volume-independent quantification using a dropper instead of a micropipette because the length of the storage channel plays the role of a volume gauge to estimate the introduced sample volume. In this study, the D/S ratios obtained with a dropper were comparable to those obtained with a micropipette, which confirmed that precise volume control is unnecessary for this PAD system. The proposed PADs were applied to the determinations of iron and bovine serum albumin using bathophenanthroline and tetrabromophenol blue as colorimetric reagents, respectively. The calibration curves showed good linear relationships with coefficients of 0.989 for iron and 0.994 for bovine serum albumin, respectively. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 0003-2654 148 11 2023 FRET probe for detecting two mutations in one EGFR mRNA 2626 2632 EN Myat Thu Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kouta Yanai Department of Interdisciplinary Science and Engineering in Health Systems, Okayama 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) 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 Technologies for visualizing and tracking RNA are essential in molecular biology, including in disease-related fields. In this study, we propose a novel probe set (DAt-probe and T-probe) that simultaneously detects two mutations in the same RNA using fluorescence resonance energy transfer (FRET). The DAt-probe carrying the fluorophore Atto488 and the quencher Dabcyl were used to detect a cancer mutation (exon19del), and the T-probe carrying the fluorophore Tamra was used to detect drug resistance mutations (T790M) in epidermal growth factor receptor (EGFR) mRNA. These probes were designed to induce FRET when both mutations were present in the mRNA. Gel electrophoresis confirmed that the two probes could efficiently bind to the mutant mRNA. We measured the FRET ratios using wild-type and double-mutant RNAs and found a significant difference between them. Even in living cells, the FRET probe could visualize mutant RNA. As a result, we conclude that this probe set provides a method for detecting two mutations in the single EGFR mRNA via FRET. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 3 2023 Utility of Comprehensive Genomic Profiling for Precise Diagnosis of Pediatric-Type Diffuse High-Grade Glioma 323 330 EN Keigo Makino Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiro Otani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Fujii Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Joji Ishida Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuichiro Hirano Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuki Suruga Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kana Washio Departments of Pediatrics, Okayama University Hospital Kenji Nishida Departments of Pathology, Okayama University Hospital Hiroyuki Yanai Departments of Pathology, Okayama University Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/65502 In the current World Health Organization classification of central nervous system tumors, comprehensive genetic and epigenetic analyses are considered essential for precise diagnosis. A 14-year-old male patient who presented with a cerebellar tumor was initially diagnosed with glioblastoma and treated with radiation and concomitant temozolomide chemotherapy after resection. During maintenance temozolomide therapy, a new contrast-enhanced lesion developed in the bottom of the cavity formed by the resection. A second surgery was performed, but the histological findings in specimens from the second surgery were different from those of the first surgery. Although genome-wide DNA methylation profiling was conducted using frozen tissue for a precise diagnosis, the proportion of tumor cells was insufficient and only normal cerebellum was observed. We then performed comprehensive genetic analysis using formalin-fixed paraffin-embedded sections, which revealed MYCN amplification without alteration of IDH1, IDH2, or Histone H3. Finally, the patient was diagnosed with pediatric-type diffuse high-grade glioma, H3-wildtype and IDH-wildtype. In conclusion, comprehensive genetic and epigenetic analysis should be considered in pediatric brain tumor cases. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 3 2023 Associations between Comorbidities and Acute Exacerbation of Interstitial Lung Disease after Primary Lung Cancer Surgery 301 309 EN Takahide Kato Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine Seigo Miyoshi Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine Chizuru Hamada Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine Yoshifumi Sano Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine Naoyuki Nogami Department of Community Medicine, Pulmonology and Cardiology, Ehime University Graduate School of Medicine Osamu Yamaguchi Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine Naohiko Hamaguchi Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine Original Article 10.18926/AMO/65495 Acute exacerbation (AE) of interstitial lung disease (ILD) is a severe complication of lung resection in lung cancer patients with ILD (LC-ILD). This study aimed to assess the predictive value of comorbidities other than ILD for postoperative AE in patients with LC-ILD. We retrospectively evaluated 68 patients with LC-ILD who had undergone lung resection. We classified them into two groups: those who had developed postoperative AE within 30 days after resection and those who had not. We analyzed patient characteristics, high-resolution computed tomography findings, clinical data, pulmonary function, and intraoperative data. The incidence of postoperative AEs was 11.8%. In univariate analysis, performance status (PS), honeycombing, forced vital capacity (FVC), and high hemoglobin A1c (HbA1c) levels without comorbidities were significantly associated with postoperative AE. Patients were divided into two groups according to cutoff levels of those four variables as determined by receiver operating characteristic curves, revealing that the rates of patients without postoperative AE differed significantly between groups. The present results suggested that preoperative comorbidities other than ILD were not risk factors for postoperative AE in patients with LC-ILD. However, a high preoperative HbA1c level, poor PS, low FVC, and honeycombing may be associated with postoperative AE of LC-ILD. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Comparison of serum sIL-2R and LDH levels in patients with intravascular large B-cell lymphoma and patients with advanced stage diffuse large B-cell lymphoma EN Yuki HIRAMI Graduate School of Health Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 オオツノコクヌストモドキにおける環境要因と性選択の相互作用 EN Katsuya KIYOSE Graduate School of Environmental and Life Science, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 過剰発現によりストレス環境への耐性を向上させる酵母遺伝子集団の性質に関する研究 EN Nozomu SAEKI Graduate School of Environmental and Life Science, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 メチル水銀による小胞体ストレス応答を介した神経細胞死誘導機構 EN Ryosuke NOMURA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Effect of Patient-Participation Continuous Nutritional Counseling in Gastric Cancer Patients who Underwent Gastrectomy EN Nobuo TAKATA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Protective Effect of Rivaroxaban Against Amyloid Pathology and Neuroinflammation Through Inhibiting PAR-1 and PAR-2 in Alzheimer's Disease Mice EN ZHIHONG BIAN Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Neuroprotective Effects of Anti-high Mobility Group Box-1 Monoclonal Antibody Against Methamphetamine-Induced Dopaminergic Neurotoxicity EN Kaori MASAI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Genomically stable gastric cancer characterized by hypomethylation in Wnt signal cascade EN Toshiaki TOSHIMA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Iron and Steel Institute of Japan Acta Medica Okayama 0915-1559 61 6 2021 Effect of Impeller and Gas Stirring on Agglomeration Behavior of Polydisperse Fine Particles in Liquid 1775 1783 EN Akito Yamaguchi Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Hitoshi Okano Department of Material and Energy Science, Graduate School of Environmental Science Syunsuke Sumitomo Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Md. Azhar Uddin Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Yoshiei Kato Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Agglomeration, coalescence and flotation of non-metallic inclusions in steel melt are effective for obtaining “clean steel.” In this study, the agglomeration and breakup behaviors of particles with a primary particle size distribution (hereinafter, polydisperse particles) in a liquid under impeller and gas stirring were compared by numerical calculations and model experiments. The particle-size-grouping (PSG) method in the numerical agglomeration model of particles was combined with a breakup term of agglomeration due to bubble bursting at the free surface. Polydisperse and monodisperse polymethylmethacrylate (PMMA) particles were used in the agglomeration experiments. The agglomeration rate of the polydisperse particles under impeller stirring was increased by an increasing energy input rate, whereas the agglomeration rate under gas stirring decreased under this condition due to the larger contribution of the breakup of agglomerated particles during bubble bursting in gas stirring. At the same energy input rate, agglomeration of polydisperse particles was larger under impeller stirring than under gas stirring. The agglomeration rate of polydisperse particles was larger than that of monodisperse particles under both impeller and gas stirring at the same energy input rate. The computational temporal changes in the total number of particles were in good agreement with the experimental results. This means that the difference in the agglomeration behaviors observed in impeller and gas stirring can be explained by the turbulent coagulation and subsequent agglomerated particle breakup in gas stirring. The computational temporal change in the number of each group approximately agreed with the experimental change in both impeller and gas stirring. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9032 10 2 2022 Association between Overall Survival and Activities of Daily Living in Patients with Spinal Bone Metastases 350 EN Yoshiteru Akezaki Division of Physical Therapy, Kochi Professional University of Rehabilitation Eiji Nakata Department of Orthopaedic Surgery, Okayama University Hospital Masato Kikuuchi Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center Shinsuke Sugihara Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center Yoshimi Katayama Department of Rehabilitation Medicine, Okayama University Hospital Haruyoshi Katayama Department of Orthopaedic Surgery, Okayama University Hospital Masanori Hamada Department of Rehabilitation Medicine, Okayama University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Hospital Objective: This study aimed to investigate the association between overall survival (OS) and activities of daily living (ADL) in patients with skeletal-related events. In this study, 265 patients whose clinical parameters were available before radiotherapy were investigated. Methods: Age, sex, ADL, pain, the primary site, spinal level of bone metastases, spinal instability, treatment strategy, including chemotherapy or palliative treatment, and OS were investigated. ADL patients with a Barthel index of >= 90 were classified as the high ADL group, while those with a score < 90 were classified as the low ADL group. For OS, patients surviving >= 160 days were classified as the non-poor prognosis group, and those who survived <160 days were classified as the poor prognosis group. Results: Age, sex, ADL, pain, the primary site, and treatment strategy for OS were different between the two groups (p < 0.1). Logistic regression analysis revealed that ADL, the primary site, and treatment strategy were significant predictors of OS (p < 0.05). High ADL, breast cancer, and chemotherapy had a positive effect on OS. Conclusions: It is suggested that improvements may be obtained by performing rehabilitation interventions to maintain and improve ADL, by constructing a system for monitoring spinal bone metastases with images before ADL decreases, and by performing interventions such as changes in treatment methods such as RT or surgery at appropriate times. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1553-7404 19 4 2023 Overexpression profiling reveals cellular requirements in the context of genetic backgrounds and environments e1010732 EN Nozomu Saeki Graduate School of Environmental and Life Science, Okayama University Chie Yamamoto Graduate School of Environmental and Life Science, Okayama University Yuichi Eguchi Biomedical Business Center, RICOH Futures BU Takayuki Sekito Graduate School of Agriculture, Ehime University Shuji Shigenobu National Institute for Basic Biology Mami Yoshimura RIKEN Center for Sustainable Resource Science Yoko Yashiroda RIKEN Center for Sustainable Resource Science Charles Boone RIKEN Center for Sustainable Resource Science Hisao Moriya Faculty of Environmental, Life, Natural Science and Technology, Okayama University Overexpression can help life adapt to stressful environments, making an examination of overexpressed genes valuable for understanding stress tolerance mechanisms. However, a systematic study of genes whose overexpression is functionally adaptive (GOFAs) under stress has yet to be conducted. We developed a new overexpression profiling method and systematically identified GOFAs in Saccharomyces cerevisiae under stress (heat, salt, and oxidative). Our results show that adaptive overexpression compensates for deficiencies and increases fitness under stress, like calcium under salt stress. We also investigated the impact of different genetic backgrounds on GOFAs, which varied among three S. cerevisiae strains reflecting differing calcium and potassium requirements for salt stress tolerance. Our study of a knockout collection also suggested that calcium prevents mitochondrial outbursts under salt stress. Mitochondria-enhancing GOFAs were only adaptive when adequate calcium was available and non-adaptive when calcium was deficient, supporting this idea. Our findings indicate that adaptive overexpression meets the cell's needs for maximizing the organism's adaptive capacity in the given environment and genetic context. Author summaryThe study aimed to investigate how overexpression of genes can aid organisms in adapting to stress. The researchers utilized a new method to identify genes in yeast that demonstrated functional adaptability when overexpressed under stress such as heat, salt, and oxidative stress. The results indicated that overexpressing specific genes, like calcium, during salt stress could counteract deficiencies and improve the organism's ability to withstand stress. The study also examined the effect of different genetic backgrounds on these genes and discovered that the impact differed among various yeast strains. Additionally, the study revealed that calcium could play a key role in adapting to salt stress by preventing mitochondrial outbursts. These findings suggest that overexpressing certain genes can help the organism maximize its adaptability to stress in a given environment and genetic context. No potential conflict of interest relevant to this article was reported.

Japan Atherosclerosis Society Acta Medica Okayama 1340-3478 30 4 2023 Association between High Pericoronary Adipose Tissue Computed Tomography Attenuation and Impaired Flow-Mediated Dilation of the Brachial Artery 364 376 EN Keishi Ichikawa 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 Yuko Ohno Department of Medical technology, Kawasaki University of Medical Welfare Kazuhiro Osawa Department of General Internal Medicine 3, Kawasaki Medical School General Medicine Center Mitsutaka Nakashima Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takahiro Nishihara 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 Hironobu Toda Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masatoki Yoshida Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Ito Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aims: Pericoronary adipose tissue (PCAT) attenuation on coronary computed tomography angiography (CTA) is a noninvasive biomarker for pericoronary inflammation and is associated with cardiac mortality. We aimed to investigate the association between PCAT attenuation and endothelial dysfunction assessed using flow-mediated dilation (FMD). Methods: A total of 119 outpatients who underwent both coronary CTA and FMD measurements were examined. PCAT attenuation values were assessed at the proximal 40-mm segments of all three major coronary arteries on coronary CTA. Endothelial function was assessed using FMD. Patients were then classified into two groups: those with endothelial dysfunction (FMD ＜4%, n=44) and those without endothelial dysfunction (FMD ≥ 4%, n=75). Results: In all three coronary arteries, PCAT attenuation was significantly higher in patients with endothelial dysfunction than in those without endothelial dysfunction. Multivariate logistic regression analysis revealed that PCAT attenuation in the right coronary artery (odds ratio [OR]=1.543; 95% confidence interval [CI]=1.004–2.369, p=0.048) and left anterior descending artery (OR=1.525, 95% CI=1.004–2.369, p=0.049) was an independent predictor of endothelial dysfunction. Subgroup analysis of patients with adverse CTA findings (significant stenosis and/or high-risk plaque) and those with coronary artery calcium score ＞100 showed that high PCAT attenuation in all three coronary arteries was a significant predictor of endothelial dysfunction. Conclusion: High PCAT attenuation was significantly associated with FMD-assessed endothelial dysfunction in patients with suspected coronary artery disease. Our results suggest that endothelial dysfunction is one of the pathophysiological mechanisms linking pericoronary inflammation to cardiac mortality. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0022-510X 447 2023 Neuroprotective effects of carnosine in a mice stroke model concerning oxidative stress and inflammatory response 120608 EN Xinran Hu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Fukui Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tian Feng Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Zhihong Bian Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haibo Yu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xiao Hu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuting Bian Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hongming Sun Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumiko Nakano Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Carnosine (β-alanyl-L-histidine) is a natural dipeptide with multiple neuroprotective properties. Previous studies have advertised that carnosine scavenges free radicals and displays anti-inflammatory activity. However, the underlying mechanism and the efficacies of its pleiotropic effect on prevention remained obscure. In this study, we aimed to investigate the anti-oxidative, anti-inflammative, and anti-pyroptotic effects of carnosine in the transient middle cerebral artery occlusion (tMCAO) mouse model. After a daily pre-treatment of saline or carnosine (1000 mg / kg / day) for 14 days, mice (n = 24) were subjected to tMCAO for 60 min and continuously treated with saline or carnosine for additional 1 and 5 days after reperfusion. The administration of carnosine significantly decreased infarct volume 5 days after the tMCAO (*p < 0.05) and effectively suppressed the expression of 4-HNE, 8-OHdG, Nitrotyrosine 5 days, and RAGE 5 days after tMCAO. Moreover, the expression of IL-1β was also significantly suppressed 5 days after tMCAO. Our present findings demonstrated that carnosine effectively relieves oxidative stress caused by ischemic stroke and significantly attenuates neuroinflammatory responses related to IL-1β, suggesting that carnosine can be a promising therapeutic strategy for ischemic stroke. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 2 2023 Three Cases of Down Syndrome with Transient Abnormal Myelopoiesis who Underwent Liver Biopsy before Induction of Low-Dose Cytarabine 215 220 EN Kana Washio Department of Pediatrics, Okayama University Hospital Kosuke Tamefusa Department of Pediatrics, Okayama University Hospital Motoharu Ochi Department of Pediatrics, Okayama University Hospital Kiichiro Kanamitsu Department of Pediatrics, National Hospital Organization Okayama Medical Center Hisashi Ishida Department of Pediatrics, Okayama University Hospital Kaori Fujiwara Department of Pediatrics, Okayama University Hospital Kenji Nishida Department of Pathology, Okayama University Hospital Kei Tamai Department of Neonatology, National Hospital Organization Okayama Medical Center Yosuke Washio Department of Pediatrics, Okayama University Hospital Junko Yoshimoto Department of Pediatrics, Okayama University Hospital Takuo Noda Department of Pediatric Surgery, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Hospital Case Report 10.18926/AMO/65153 Among patients with transient abnormal myelopoiesis (TAM) associated with Down syndrome, approximately 20% die within 6 months from multiorgan failure, especially liver fibrosis. We experienced three children with TAM who had low white blood cell counts but increased bilirubin levels. Here, we discuss the detailed clinical courses of these patients, including the pathological findings of liver biopsies. Our cases, together with previous literature, suggest that liver biopsy can be performed safely and provides useful information, especially regarding disease activities, and that low-dose cytarabine is a reasonable option to prevent early death in TAM patients with liver dysfunction. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 2 2023 Locally Advanced Rectal Cancer Invading the Gluteus Maximus Muscle Completely Responded to Total Neoadjuvant Therapy 209 213 EN Masaki Sakamoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/65152 A 70-year-old male with anal pain and fever was diagnosed with rectal cancer perforation and abscess in the right gluteus maximus (GM) muscle. He underwent a transverse colon colostomy followed by preoperative capecitabine+oxaliplatin. Some local control was achieved but a residual abscess was observed in the right GM muscle. To secure circumferential resection margin by tumor reduction, he received chemoradiotherapy as total neoadjuvant therapy (TNT) and underwent laparoscopic abdominoperineal resection, D3 lymph node dissection, combined coccyx resection, and partial resection of the right GM muscle. The skin defect and pelvic dead space were filled with a right lateral vastus lateral great muscle flap. Histopathologically, the resected specimen showed no tumor cells in the primary tumor or lymph nodes, indicating a pathological complete response (pCR). This case suggests that TNT might improve the R0 resection and pCR rates and overall survival. No potential conflict of interest relevant to this article was reported.

Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 63 1 2023 Comparison of serum sIL-2R and LDH levels in patients with intravascular large B-cell lymphoma and patients with advanced stage diffuse large B-cell lymphoma 25 31 EN Yuki Hirami Department of Nursing, Okayama University Graduate School of Health Sciences Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Tomohiro Urata Department of Hematology and Oncology, Okayama University Hospital Michiko Morimoto Department of Nursing, Okayama University Graduate School of Health Sciences Yukina Maekawa Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshito Nishimura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Intravascular large B-cell lymphoma (IVL) is a rare type of lymphoma characterized by tumor growth selectively within the vessels. The 5th edition of the World Health Organization classification defines IVL as a large B-cell lymphoma, the same as diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). Since the clinical manifestations of IVL are nonspecific, the diagnosis is time-consuming, and the course is often fatal. Serum soluble interleukin-2 receptor (sIL-2R) and serum lactate dehydrogenase (LDH) levels are known to be elevated in a variety of lymphomas. However, the mechanism of sIL-2R elevation in B-cell lymphomas is not fully understood. In this study, we analyzed the serum level of laboratory findings, including sIL-2R and LDH, as well as the presence of B symptoms in 39 patients with IVL, and compared them with 56 patients with stage IV DLBCL. Both sIL-2R and LDH levels were significantly higher in IVL than in DLBCL (p = 0.035 andp = 0.002, respectively). In IVL, there were no significant differences in both sIL-2R and LDH levels between patients with and without B symptoms (p = 0.206 andp = 0.441, respectively). However, in DLBCL, both sIL-2R and LDH levels were significantly higher in the presence of B symptoms (p = 0.001 andp < 0.001, respectively). The high sIL-2R and LDH levels in IVL may be related to the peripheral blood microenvironment, but further studies are needed to verify this. No potential conflict of interest relevant to this article was reported.

eLife Sciences Publications Ltd. Acta Medica Okayama 2050-084X 12 2023 Chloride ions evoke taste sensations by binding to the extracellular ligand-binding domain of sweet/umami taste receptors e84291 EN Nanako Atsumi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiko Yasumatsu Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuriko Takashina School of Pharmaceutical Sciences, Okayama University Chiaki Ito Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Norihisa Yasui Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Robert F. Margolskee Monell Chemical Senses Center Atsuko Yamashita Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Salt taste sensation is multifaceted: NaCl at low or high concentrations is preferably or aversively perceived through distinct pathways. Cl- is thought to participate in taste sensation through an unknown mechanism. Here, we describe Cl- ion binding and the response of taste receptor type 1 (T1r), a receptor family composing sweet/umami receptors. The T1r2a/T1r3 heterodimer from the medaka fish, currently the sole T1r amenable to structural analyses, exhibited a specific Cl- binding in the vicinity of the amino-acid-binding site in the ligand-binding domain (LBD) of T1r3, which is likely conserved across species, including human T1r3. The Cl- binding induced a conformational change in T1r2a/T1r3LBD at sub- to low-mM concentrations, similar to canonical taste substances. Furthermore, oral Cl- application to mice increased impulse frequencies of taste nerves connected to T1r-expressing taste cells and promoted their behavioral preferences attenuated by a T1r-specific blocker or T1r3 knock-out. These results suggest that the Cl- evokes taste sensations by binding to T1r, thereby serving as another preferred salt taste pathway at a low concentration. No potential conflict of interest relevant to this article was reported.