Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Pseudohypoxia induced by iron chelators preserves working memory performance in aged mice 11550 EN Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiaki Iwasaki Health Service Section, Environment Health & Safety Intelligence Department, Okayama University Tomonari Kasai Department of Applied Energy, Graduate School of Engineering, Nagoya University Toru Yamashita Department of Neurology, Graduate School of Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shiho Komaki Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Hamada 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 Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Pseudohypoxia refers to a physiological condition wherein hypoxia-inducible factor (HIF) is pharmacologically upregulated under normoxia, thereby modulating immune responses. We hypothesized that pseudohypoxia, induced by iron chelators, may similarly potentiate systemic immune responses in aged mice, concurrently triggering neuro-regenerative signaling pathways and enhancing cognitive performance. In this study, aged mice (43–48 weeks old) were orally administered two iron chelators, Super Polyphenol 10 (SP10) or Roxadustat, to induce a pseudohypoxia. An 8-week oral regimen of SP10 and Roxadustat significantly preserved working memory, as assessed by the Y-maze test (YMT). White blood cell counts and hippocampal volume, as assessed by magnetic resonance imaging (MRI), were elevated in the treatment groups relative to controls. Pseudohypoxia induced by SP10 tended to enhance neuro-regenerative signaling, specifically involving the Tau and JNK pathways, and potentially modulated Doublecortin (DCX) expression, although statistical significance was limited by sample size. Importantly, inflammatory markers, such as ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP), were not elevated by treatment. Collectively, these findings suggest that pseudohypoxia induced by iron chelators preserves working memory performance accompanied by leukocytosis, without concomitant neuroinflammation. No potential conflict of interest relevant to this article was reported.

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

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

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.

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

Elsevier BV Acta Medica Okayama 1341-321X 32 3 2026 Tick-borne pathogens in ticks collected from Humans: A prospective clinical pilot study 102931 EN Shinnosuke Fukushima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaomi Sumida Numakuma Hospital Osamu Kawamata Numakuma Hospital Yoshimi Hidani Numakuma Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Tick-borne diseases (TBDs), particularly Japanese spotted fever, are an increasing public health concern in Japan. Data on pathogens carried by ticks removed directly from patients and their associated clinical outcomes remain limited. This prospective study investigated pathogen carriage in patient-derived ticks and evaluated the clinical risk of TBDs. Between April and October 2025, ticks were collected from patients presenting with tick bites at two medical institutions in Western Japan. Ticks were morphologically identified and spotted fever group rickettsiae (SFGR) was detected by nested PCR targeting the 17-kDa antigen gene, followed by sequence analysis. Clinical data, including patient background, antibiotic prescriptions, and outcomes, were reviewed. Clinical information was available for 70 patients (median age; 75 years), of whom 88.6% were prescribed prophylactic antibiotics. Ticks were collected from 60 patients (85.7%), and seven adults without antibiotic prophylaxis were followed for disease onset. Sixty-two ticks, predominantly Amblyomma testudinarium (88.7%), were analyzed. SFGR was detected in eight ticks (12.9%), including seven A. testudinarium and one Ixodes nipponensis, collected from seven patients. Two patients bitten by Rickettsia tamurae–carrying ticks were observed for one month without antibiotics and remained asymptomatic. In this prospective analysis, no clinically apparent rickettsiosis was observed following bites from R. tamurae–positive ticks without antibiotic prophylaxis; however, subclinical infection could not be excluded. Despite the small sample size, our findings suggest that the clinical risk associated with R. tamurae infection may be low. Direct analysis of removed ticks from patients may help characterize pathogen reservoirs and inform targeted approaches to TBDs. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 18 1 2026 Saliva as a Reliable and Non-invasive Sample for Detecting Influenza A in Severe Acute Respiratory Infection Cases e100872 EN Junko S Takeuchi Department of Academic-Industrial Partnerships Promotion, Center for Clinical Sciences, Japan Institute for Health Security Nobuaki Matsunaga Antimicrobial Resistance (AMR) Clinical Reference Center, Japan Institute for Health Security Ai Tsukada Antimicrobial Resistance (AMR) Clinical Reference Center, Japan Institute for Health Security Noriko Iwamoto Disease Control and Prevention Center, Japan Institute for Health Security Noriko Fuwa Disease Control and Prevention Center, Japan Institute for Health Security Takahiro Ichikawa Department of Infectious Diseases, Sapporo City General Hospital Yasuyuki Kato Department of Infectious Diseases, International University of Health and Welfare (IUHW) Narita Hospital Yuka Tomita Department of Infectious Diseases, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital Hiroki Kitagawa Department of Infectious Diseases, Hiroshima University Hospital Masaya Yamato Department of General Internal Medicine and Infectious Diseases, Rinku General Medical Center Tetsuji Aoyagi Department of Clinical Infectious Diseases, Tohoku University Graduate School of Medicine Hideharu Hagiya Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryota Hase Department of Infectious Diseases, Japanese Red Cross Narita Hospital Shuji Hatakeyama Division of Infectious Diseases, Jichi Medical University Hospital Tohru Inaba Department of Infection Control and Laboratory Medicine, Kyoto Prefectural University of Medicine Koichi Izumikawa Yoshio Takesue Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences Moto Kimura Department of Academic-Industrial Partnerships Promotion, Center for Clinical Sciences, Japan Institute for Health Security Norio Ohmagari Disease Control and Prevention Center, Japan Institute for Health Security Background Nasopharyngeal swab sampling remains the gold standard for influenza diagnosis; however, it has several limitations, including dependence on medical staff, invasiveness, potential for nosocomial transmission, and occupational exposure risk. Non-invasive alternatives, such as saliva and nasal vestibular swabs, may improve patient comfort and participation in clinical studies. In addition, diagnosis with reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) is often delayed because it requires trained laboratory technicians and facilities with appropriate laboratory settings. Although rapid diagnostic devices such as the GenPad® offer potential alternatives to RT-qPCR, their performance with non-invasive samples remains insufficiently explored. This study addresses the two key questions for influenza detection in severe acute respiratory infection (SARI) cases: (i) whether saliva or nasal vestibular swab samples serve as suitable alternatives to nasopharyngeal swab samples, and (ii) whether the GenPad® provides a reliable option for detecting influenza using saliva samples. Methodology A prospective observational study was conducted with 16 inpatients classified as having SARIs and diagnosed with influenza between December 2024 and March 2025 in Japan. Paired saliva and nasal vestibular swab samples were collected 1-9 (median = 3.5) days after symptom onset. RT-qPCR testing was performed according to the National Institute of Infectious Diseases protocol. Saliva samples were also tested using the GenPad® system. Comparisons between sample types and diagnostic methods were analyzed using the exact McNemar's test. Results Among the 16 influenza-positive patients, saliva samples demonstrated higher sensitivity (87.5%) than nasal vestibular swabs (31.3%) in RT-qPCR when compared with the diagnostic results obtained from nasopharyngeal swabs. A comparison of RT-qPCR results between saliva and nasal vestibular swabs revealed a total agreement of 43.8%, with exact McNemar's test showing a significant difference (p = 0.0039). While nasal vestibular swabs showed inconsistent results, saliva samples consistently tested positive, particularly within seven days of symptom onset (100% positive agreement). The GenPad®, a rapid diagnostic device, showed promising performance (92.9%) using saliva samples compared to RT-qPCR. Conclusions Saliva is a reliable non-invasive alternative to nasopharyngeal swabs for influenza detection in SARI cases, particularly within seven days of symptom onset, whereas nasal vestibular swabs show lower sensitivity. Additionally, the GenPad® provides comparable performance to RT-qPCR using saliva samples, offering a rapid, portable diagnostic option. These approaches may mitigate discomfort, minimize infection risk for healthcare workers, and improve testing capacity. However, the absence of influenza-negative controls and the small sample size (n = 16) substantially limit the assessment of diagnostic accuracy and specificity. As a result, the broader applicability of our findings should be interpreted with caution, and further studies are required to validate these observations. No potential conflict of interest relevant to this article was reported.

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

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

China Anti-cancer Association Acta Medica Okayama 2095-3941 2026 SPRED2 suppresses the stemness of hepatocellular carcinoma through the p53/miR-506-3p/KLF4 pathway EN Tong Gao Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sachio Ito Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aye Moh-Moh-Aung Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tianyi Wang 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 Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objective: We previously reported that endogenous Sprouty-related, EVH1 domain-containing protein 2 (SPRED2), an inhibitor of the Ras/Raf/ERK-MAPK pathway, controls hepatocellular carcinoma (HCC) cell stemness by downregulating the expression of pluripotency factors, such as Nanog, c-Myc, and KLF4, in an ERK-dependent fashion. However, the exact mechanisms by which SPRED2 regulates HCC cell stemness have not been established. Methods: Three human HCC cell lines [HepG2 (parental and SPRED2-deficient), HLE, and Hep3B] were used. Cells were transfected to downregulate or overexpress proteins. Western blot and RT-qPCR were used to evaluate the level of protein and mRNA expression. Co-immunoprecipitation and ChIP-qPCR were used to examine protein-protein interactions and the activation of gene transcription. Clinical HCC tissues were also used to validate in vitro data. Results: KLF4 was identified as the major pluripotency factor responsible for SPRED2-mediated downregulation of HCC cell stemness and KLF4 expression was regulated by miR-506-3p. SPRED2 formed a protein complex with the tumor suppressor (p53) and upregulated miR-506 gene transcription by binding to the promoter region, resulting in subsequent downregulation of KLF4 mRNA expression. There was a negative correlation between KLF4 expression and miR-506-3p and a positive correlation between miR-506-3p expression and SPRED2 in human HCC samples, highlighting the relevance of the study findings. Conclusions: The current study revealed a novel SPRED2/p53/miR-506-3p/KLF4 axis through which SPRED2 contributes to the suppression of HCC cell stemness and provides a potential new target to prevent HCC progression. No potential conflict of interest relevant to this article was reported.

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

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

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

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.

Elsevier BV Acta Medica Okayama 2772-5723 5 2 2026 Feasibility and Diagnostic Utility of Mucosal T-Cell Flow Cytometry for Intestinal Graft-Versus-Host Disease 100820 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takumi Kondo Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daisuke Ennishi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nobuharu Fujii Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mai Hiramatsu Division of Medical Support, Okayama University Hospital Araki Hirabata Division of Medical Support, Okayama University Hospital Takahide Takahashi Division of Medical Support, Okayama University Hospital Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background and Aims: Timely diagnosis of intestinal complications after hematopoietic stem cell transplantation (HSCT), including graft-versus-host disease (GVHD), transplant-associated thrombotic microangiopathy, and cytomegalovirus infection, is essential for appropriate management. This study evaluated whether mucosal T-cell profiling from endoscopic biopsies could support the diagnosis of these post-transplant conditions. Methods: We prospectively analyzed 58 intestinal biopsy specimens from 21 post-HSCT patients. Paired samples were obtained from the stomach and duodenum during upper endoscopy and from the ileum and large intestine during colonoscopy. Lymphocytes were isolated from each specimen and analyzed using flow cytometry. These data were integrated with those of a previously collected cohort (35 patients, 51 samples) for comparative immunophenotypic analysis across histologically defined groups. Results: Duodenal biopsies yielded more lymphocytes than did gastric biopsies (mean ± standard deviation: 532 ± 823 vs 233 ± 392 cells; P = .070), with comparable yields between the ileum and colon. Among 41 evaluable cases, the CD56+:CD3+ ratio was significantly lower in patients with GVHD (5.5 ± 2.2%) than in those with nonspecific or no inflammation (28.4 ± 16.3%; P = .006). A cutoff value of <11% provided 85.7% sensitivity and 83.3% specificity for diagnosing GVHD (area under the curve = 0.91). Conclusion: Mucosal T-cell profiling using endoscopic biopsies is feasible and may aid in the diagnosis of GVHD after HSCT. A decreased CD56+:CD3+ ratio is a promising marker for distinguishing GVHD from other post-transplant intestinal conditions. No potential conflict of interest relevant to this article was reported.

Institute of Electrical and Electronics Engineers (IEEE) Acta Medica Okayama 0018-9456 74 2025 Small Distance Increment Method for Measuring Complex Permittivity With mmWave Radar 6009610 EN Hang Song Research Institute for Semiconductor Engineering, Hiroshima University Hyun Joon Kim Department of Transdisciplinary Science and Engineering, Institute of Science Tokyo Mingxia Wan Department of Transdisciplinary Science and Engineering, Institute of Science Tokyo Bo Wei Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takamaro Kikkawa Research Institute for Semiconductor Engineering, Hiroshima University Jun-Ichi Takada Department of Transdisciplinary Science and Engineering, Institute of Science Tokyo Measuring the complex permittivity of material is essential in many scenarios, such as quality checks in material manufacturing. Generally, measurement methods for characterizing the material are based on the use of a vector network analyzer (VNA), which is large and not easy for on-site measurement, especially in high-frequency range such as millimeter wave (mmWave). In addition, some measurement methods require the destruction of samples, which is not suitable for nondestructive inspection. In this work, a small distance increment (SDI) method is proposed to nondestructively measure the complex permittivity of a material. In SDI, the transmitter and receiver are formed as a monostatic radar, which is facing toward the material under test (MUT). During the measurement, the distance between the radar and the MUT changes with small increments, and the signals are recorded at each position. A mathematical model is formulated to depict the relationship among the complex permittivity, distance increment, and measured signals. By fitting the model, the complex permittivity of MUT is estimated. To implement and evaluate the proposed SDI method, a commercial off-the-shelf (COTS) mmWave radar is utilized, and the measurement system is developed. Then, the evaluation was carried out on the acrylic plate. With the proposed method, the estimated complex permittivity of the acrylic plate shows good agreement with the literature values, demonstrating the efficacy of the SDI method for characterizing the complex permittivity of the material. No potential conflict of interest relevant to this article was reported.

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

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

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

American Society for Clinical Investigation Acta Medica Okayama 2379-3708 10 24 2025 Enhancement of drug delivery through fibroblast activation protein–targeted near-infrared photoimmunotherapy e195776 EN Seitaro Nishimura Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Tasuku Matsumoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Yasushige Takeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Tatsuya Takahashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Hijiri Matsumoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Kento Kawasaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Hotaka Kawai Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Tomoyoshi Kunitomo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Masaaki Akai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Teruki Kobayashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Noriyuki Nishiwaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Hajime Kashima Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Takuya Kato Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Toshiaki Ohara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Yasuhiro Shirakawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Peter L. Choyke Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIH Hisataka Kobayashi Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIH Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science The tumor microenvironment plays a key role in cancer progression and therapy resistance, with cancer-associated fibroblasts (CAFs) contributing to desmoplasia, extracellular matrix (ECM) remodeling, and elevated interstitial fluid pressure, all of which hinder drug delivery. We investigated fibroblast activation protein–targeted (FAP-targeted) near-infrared photoimmunotherapy (NIR-PIT) as a strategy to improve drug penetration in CAF-rich tumors. In clinical esophageal cancer samples, FAP expression strongly correlated with increased collagen I, hyaluronic acid, and microvascular collapse. CAF-rich 3D spheroids demonstrated elevated ECM deposition and significantly impaired drug uptake compared with CAF-poor models. FAP-targeted NIR-PIT selectively reduced CAFs, reduced ECM components, and restored drug permeability. In vivo, FAP-targeted NIR-PIT enhanced the accumulation of panitumumab and Abraxane in CAF-rich tumors and improved antitumor efficacy when combined with chemotherapy. These findings highlight FAP-targeted NIR-PIT as a promising therapeutic approach to remodel the tumor stroma and overcome drug resistance in desmoplastic solid tumors. No potential conflict of interest relevant to this article was reported.

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

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

Elsevier BV Acta Medica Okayama 0169-555X 468 2025 Surface exposure ages of middle–late Pleistocene marine and fluvial terraces along the northern and southern Sanriku coasts, Northeast Japan 109497 EN Sachi Wakasa Institute of Regional Innovation, Hirosaki University Tatsuya Ishiyama Earthquake Research Institute, University of Tokyo Daisuke Hirouchi Faculty of Education, Shinshu University Nobuhisa Matta Faculty of Education, Okayama University Natsuko Fujita Tono Geoscience center, Japan Atomic Energy Agency Tomoo Echigo Kankyo Chisitsu, Co. To estimate long-term rates of coastal uplift along the northern Pacific coast of Northeast Japan, we determined the surface exposure ages of marine and fluvial terraces based on terrestrial in situ cosmogenic radionuclide dating of exposed bedrock surfaces. Based on reinterpretation of marine and fluvial terraces, we collected samples from the northern and southern Sanriku coast. The surface exposure ages from 10Be concentrations in quartz calculated from the measured 10Be/9Be ratios commonly suggest MIS 5 and MIS 7 for the marine and fluvial terraces and averaged coastal uplift rates of ca. 0.25 ± 0.15 and 0.4 mm/yr along the northern and southern Sanriku coast at intermediate timescales. The results may demonstrate different styles of crustal strain accommodation in the northern Northeast Japan arc above the subducting Pacific plate. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 63 13 2024 Activated CD4+ T Cell Proportion in the Peripheral Blood Correlates with the Duration of Cytokine Release Syndrome and Predicts Clinical Outcome after Chimeric Antigen Receptor T Cell Therapy 1863 1872 EN Wataru Kitamura Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Shuntaro Ikegawa Department of Hematology and Oncology, Okayama University Hospital, Japan Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Chihiro Kamoi Department of Hematology and Oncology, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Division of Clinical Laboratory, Okayama University Hospital Nobuharu Fujii Division of Blood Transfusion, Okayama University Hospital Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Objective Chimeric antigen receptor (CAR) T cell therapy is an emerging and effective therapy for relapsed or refractory diffuse large B cell lymphoma (R/R DLBCL). The characteristic toxicities of CAR T cell therapy include cytokine release syndrome (CRS) and prolonged cytopenia. We investigated the factors associated with these complications after CAR T cell therapy by analyzing lymphocyte subsets following CAR T cell infusion. Methods We retrospectively analyzed peripheral blood samples on days 7, 14, and 28 after tisagenlecleucel (tisa-cel) infusion by flow cytometry at our institution between June 2020 and September 2022. Patients Thirty-five patients with R/R DLBCL who received tisa-cel therapy were included. Results A flow cytometry-based analysis of blood samples from these patients revealed that the proportion of CD4+CD25+CD127+ T cells (hereafter referred to as "activated CD4+ T cells" ) among the total CD4+ T cells on day 7 after tisa-cel infusion correlated with the duration of CRS (r=0.79, p<0.01). In addition, a prognostic analysis of the overall survival (OS) using time-dependent receiver operating characteristic curves indicated a significantly more favorable OS and progression-free survival of patients with a proportion of activated CD4+ T cells among the total CD4+ T cells <0.73 (p=0.01, and p<0.01, respectively). Conclusion These results suggest that the proportion of activated CD4+ T cells on day 7 after tisa-cel infusion correlates with the CRS duration and predicts clinical outcomes after CAR T cell therapy. Further studies with a larger number of patients are required to validate these observations. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2452-199X 57 2026 Robust adhesion between solid-state hydroxyapatite and bone tissue through surface demineralization 632 645 EN Shichao Xie Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiro Okada Division of Biomaterials Science and Engineering, Graduate School of Dentistry, Tohoku University Haruyuki Aoyagi Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihisa Otaka Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xiaofeng Yang Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayoshi Nakano Division of Materials and Manufacturing Science, Graduate School of Engineering, The University of Osaka Takuya Matsumoto Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objective: Current bone adhesives typically lack adequate mechanical strength, long-term stability, or biocompatibility. To address these limitations, we designed a new adhesion strategy using a solid-state hydroxyapatite (HAp) adhesive in combination with bone surface demineralization. Methods: Solid-state HAp adhesives were synthesized via wet chemical precipitation and heat treatment. Cortical bone specimens were partially demineralized with phosphoric acid (H3PO4) or ethylenediaminetetraacetic acid (EDTA), and characterized using scanning electron microscopy (SEM) and attenuated total reflectance–Fourier transform infrared spectroscopy (ATR-FTIR). Shear adhesion strength of HAp to demineralized bone was measured over time. In vivo fixation was assessed in rats using micro-computed tomography and histology. Statistical analysis used Tukey-Kramer tests after normality and variance checks. Results: Although the HAp adhesive failed to adhere to non-demineralized bone, effective adhesion was achieved on the surface-demineralized bone tissue. Shear adhesion strength was significantly higher in EDTA-treated samples (238.4 kPa at 10 h) compared to H3PO4-treated samples (102.9 kPa at 1 h), with performance correlating with demineralization depth. ATR-FTIR and SEM analyses revealed that EDTA preserved collagen's triple-helix structure and free water content, both enhancing adhesion. Animal experiments confirmed stable fixation of HAp adhesive to demineralized bone tissue. Conclusions: Surface demineralization enabled strong adhesion of the solid-state HAp adhesive to bone by exposing collagen swollen with water. Adhesion strength was influenced by structural changes in the demineralized layer, and the adhesive provided stable in vivo fixation, supporting its potential for bone-anchored biomedical applications. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 COVID-19 and the Risks of Migraine and Headache: A Mendelian Randomization Study 413 419 EN Zhiyun Jiang Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University Ying Xi Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University Original Article 10.18926/AMO/69843 Several observational studies suggested that migraine headache attacks were associated with coronavirus disease 2019 (COVID-19). We investigated genetic causal links between COVID-19 phenotypes and the development of headache and migraine, including migraine with aura (MA) and migraine without aura (MO). We conducted a two-sample Mendelian randomization (MR) analysis to estimate the genetic association in European populations. The inverse-variance weighted (IVW) method was used as the main approach in the MR analyses, together with weighted median and MR-Egger methods. We also performed a series of sensitivity tests to assess the robustness of the MR results. The MR results demonstrated that COVID-19 severity, hospitalization, and susceptibility had no causal effect on the risks of headache, migraine, MA, or MO. No horizontal pleiotropy was detected, and the results were robust as supported by the sensitivity analysis findings. Our analyses identified no casual effect of COVID-19 severity, hospitalization, or susceptibility on the risks of headache or migraine in European populations. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-3921 14 9 2025 Clinical Evaluation of Oxidative Stress Markers in Patients with Long COVID During the Omicron Phase in Japan 1068 EN Osamu Mese 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 Yasue Sakurada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu 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 Satoru Morita Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Eguchi Biobank Center, Mie University Hospital Sanae Fukuda Department of Health Welfare Sciences, Kansai University of Welfare Sciences Junzo Nojima Department of Laboratory Medicine, Yamaguchi University Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences To characterize changes in markers of oxidative stress for the clinical evaluation of patients with long COVID, we assessed oxidative stress and antioxidant activity based on serum samples from patients who visited our clinic between May and November 2024. Seventy-seven patients with long COVID (41 [53%] females and 36 [47%] males; median age, 44 years) were included. Median [interquartile range] serum levels of diacron-reactive oxygen metabolites (d-ROM; CARR Unit), biological antioxidant potential (BAP; μmol/L), and oxidative stress index (OSI) were 533.8 [454.9–627.6], 2385.8 [2169.2–2558.1] and 2.0 [1.7–2.5], respectively. Levels of d-ROMs (579.8 vs. 462.2) and OSI (2.3 vs. 1.8), but not BAP (2403.4 vs. 2352.6), were significantly higher in females than in males. OSI levels positively correlated with age and body mass index, whereas BAP levels negatively correlated with these parameters. d-ROM and OSI levels were significantly associated with inflammatory markers, including C-reactive protein (CRP) and fibrinogen, whereas BAP levels were inversely correlated with CRP and ferritin levels. Notably, serum free thyroxine levels were negatively correlated with d-ROMs and OSI, whereas cortisol levels were positively correlated with d-ROMs. Among long COVID symptoms, patients reporting brain fog exhibited significantly higher OSI levels (2.2 vs. 1.8), particularly among females (d-ROMs: 625.6 vs. 513.0; OSI: 2.4 vs. 2.0). The optimal OSI cut-off values were determined to be 1.32 for distinguishing long COVID from healthy controls and 1.92 for identifying brain fog among patients with long COVID. These findings suggest that oxidative stress markers may serve as indicators for the presence or prediction of psycho-neurological symptoms associated with long COVID in a gender-dependent manner. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 0883-2927 187 2025 Nitrogen distribution and nitrogen isotope fractionation in synthetic 2:1 phyllosilicates under hydrothermal conditions at 200 °C and saturated vapor pressure 106403 EN Jaeguk Jo Graduate School of Natural Science and Technology, Okayama University Toshiro Yamanaka Graduate School of Natural Science and Technology, Okayama University Youko Miyoshi Research Institute for Geo-Resources and Environment, Geological Survey of Japan, National Institute of Advanced Industrial Science and Technology (AIST) Masaya Suzuki Research Institute for Geo-Resources and Environment, Geological Survey of Japan, National Institute of Advanced Industrial Science and Technology (AIST) Yoshihiro Kuwahara Department of Environmental Changes, Faculty of Social and Cultural Studies, Kyushu University Isao Kadota Graduate School of Natural Science and Technology, Okayama University Hitoshi Chiba Graduate School of Natural Science and Technology, Okayama University Bum Han Lee Critical Minerals Research Center, Korea Institute of Geoscience & Mineral Resources (KIGAM) This study investigates nitrogen distribution and isotope fractionation within synthetic 2:1 phyllosilicates, simulating submarine hydrothermal environments at 200 °C and saturated vapor pressure. XRD and EDS results revealed the potential coexistence of multiple cations in the interlayer of synthetic 2:1 phyllosilicate, concurrently suggesting cation substitution in the tetrahedral and/or octahedral sheets. Meanwhile, the iron-enriched 25-5 sample exhibited restricted interlayer expansibility. NH4+ absorptions were identified in the NH4-stretching (3200–2800 cm−1) and NH4-bending (1450–1400 cm−1) regions, with wavenumber shifts indicating the influence of interlayer water removal. At pH 10.56, over 95% of nitrogen was released into the gas phase, while at pH 8.88, nitrogen proportions in the liquid and gas phases were comparable (average 48–49%). Experiments with iron at pH ∼8.80 showed that the nitrogen proportion in the gas phase (average 28%) was more than twofold lower than that in the liquid phase (average 68%). Equilibrium isotope fractionation factors indicated discernible preference for heavier nitrogen isotopes in the solid phase (αsolid-liquid = 1.009–1.021 and αsolid-gas = 1.011–1.027). The αliquid-gas range for sample 25–2 was 1.001–1.008, while that for the iron-enriched composite 25–5 was 0.997–1.010. Our experimental studies have confirmed that, in the absence of exchange interactions with external substances possessing different nitrogen isotope ratios, nitrogen isotope fractionation between ammonium and ammonia, controlled by variations in temperature and pH during mineralization, plays a crucial role in the variation of nitrogen isotope ratios. Additionally, we confirmed that metal-amines influence nitrogen isotope fractionation by modulating ammonia gas emission. These findings enhance our understanding of nitrogen cycling across the gas, liquid, and solid phases in submarine hydrothermal systems. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2504-3129 6 4 2025 Drip Fertigation in Greenhouse Eggplant Cultivation: Reducing N2O Emissions and Nitrate Leaching 116 EN Wataru Shiraishi Kochi Prefectural Agricultural Research Center Shion Nishimura Department of Bioresource Production Science, United Graduate School of Agriculture, Ehime University Morihiro Maeda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hideto Ueno Department of Bioresource Production Science, United Graduate School of Agriculture, Ehime University Drip fertigation (DF) is a sustainable agricultural management technique that optimizes water and nutrient usage, enhances crop productivity, and reduces environmental impact. Herein, we compared the effects of DF and conventional fertilization (CF) with a basal fertilizer on yield, soil inorganic nitrogen dynamics, N2O emissions, and nitrogen leaching during facility-grown eggplant cultivation. The experiment was conducted in a greenhouse from September 2023 to May 2024, with treatments arranged in three rows and three replicates. Soil, gas, and water samples were collected and analyzed throughout the growing season. The results revealed that the DF treatment produced yields comparable to those obtained with the CF treatment while significantly reducing nitrogen and phosphorus inputs. DF effectively prevented excessive nitrogen accumulation in the soil and reduced nitrogen loss through leaching and gas emissions. N2O emissions were significantly lower by more than 60% under DF than under CF. Precise nutrient management in DF suppressed nitrification and denitrification processes, mitigating N2O emissions. DF also significantly reduced nitrogen leaching by more than 70% compared with that in CF. These findings demonstrate that DF effectively enhances agricultural sustainability by improving nutrient use efficiency, reducing greenhouse gas emissions, and minimizing nitrogen leaching during the cultivation of facility-grown eggplant. No potential conflict of interest relevant to this article was reported.

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

MDPI AG Acta Medica Okayama 2304-6767 13 12 2025 Effects of miR-128-3p on Renal Inflammation in a Rat Periodontitis Model 577 EN Mohammad Nurhamim Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yixuan Zhang Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Momoko Nakahara Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daiki Fukuhara Department of Preventive Dentistry, Okayama University Hospital Yosei Nagashima Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayuki Maruyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Manabu Morita Department of Oral Health, Takarazuka University of Medical and Health Care Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: The study aim was to investigate the effects of extracellular vesicles (EVs) derived miR-128-3p on renal inflammation using a rat periodontitis model. Methods: Ten-week-old male Wistar rats were divided into two groups: a control (n = 8) and a lipopolysaccharides (LPS) group (n = 8). The LPS group received LPS (Porphyromonas gingivalis) injection in the gingiva for 7 days. At the end of the experiment, plasma, gingival tissue, and kidney samples were collected. Hematoxylin and eosin staining was performed to evaluate the glomerular tissue injury score. Bioinformatic analysis was conducted to identify potential target genes of miR-128-3p. The reverse transcription-quantitative polymerase chain reaction was performed to evaluate miR-128-3p, inflammatory, pro-inflammatory cytokine, chemokine and predicting gene’s expression. The control and LPS groups were compared using Welch’s t-test. p-values < 0.05 were considered to indicate statistical significance. Results: The kidney glomerular tissue injury score was significantly higher in the LPS than in the control group. miR-128-3p expression in the LPS group was significantly higher in the gingival tissue and plasma. mRNAs (interleukin [IL]-1β, tumor necrosis factor [TNF]-α, C-X3-C motif chemokine ligand 1 [CX3CL1], and C-X-C motif chemokine ligand 7 [CXCL7]) expression was higher in the kidney of the LPS group. The potential target genes of activin A receptor type I (Acvr1), ribosomal protein S6 kinase B1 (Rps6kb1), and transforming growth factor beta receptor type 1 (Tgfbr1) were significantly lower in the kidneys of the LPS group. Conclusions: EVs-derived miR-128-3p in LPS induced periodontitis may cause kidney inflammation which may be mediated by, Rps6kb1, Tgfbr1, and Acvr1. No potential conflict of interest relevant to this article was reported.

Ceramic Society of Japan Acta Medica Okayama 1348-6535 133 7 2025 Underwater superoleophobic NaNbO3-based photocatalyst thin films prepared on bare soda-lime glass by sol–gel process 393 399 EN Shunsuke Nishimoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuya Kageyama Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Shusuke Egusa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshikazu Kameshima Graduate School of Environmental, Life, Natural Science and Technology, Okayama University A self-cleaning flat transparent thin photocatalyst film was prepared on a bare soda-lime glass by a simple method using niobium alkoxide solution, which is a common coating solution for the sol–gel method. The film consisted of crystalline NaNbO3 and Na2Nb2O6·H2O phases. It was suggested that NaNbO3 and Na2Nb2O6·H2O were directly formed between the soda-lime glass and the niobium alkoxide coating solution during the heat treatment. Under UV irradiation, the film surface exhibited low photocatalytic oxidation activity and excellent photo-induced hydrophilicity. The hydrophilic state of the sample was maintained for 1 month in the dark, while the hydrophilicity of TiO2 sample prepared by a sol–gel method was decreased within 5 days in the dark. Additionally, the surface demonstrated excellent underwater oil repellency toward n-hexadecane and oleic acid and the ability to remove the adsorbed oily contaminant in water. These properties were also superior to those of the TiO2 surface. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 0944-1174 60 5 2025 Diagnostic accuracy and cut-off values of serum leucine-rich alpha-2 glycoprotein for Crohn’s disease activity in the small bowel 573 582 EN Muneyori Okita Department of Biostatistics, Nagoya University Graduate School of Medicine Kento Takenaka Department of Gastroenterology and Hepatology, Institute of Science Tokyo Fumihito Hirai Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine Shinya Ashizuka Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine Hideki Iijima Osaka International Medical & Science Center, Osaka Keisatsu Hospital Shigeki Bamba Department of Fundamental Nursing, Shiga University of Medical Science Toshimitsu Fujii Department of Gastroenterology and Hepatology, Institute of Science Tokyo Kenji Watanabe Department of Internal Medicine for Inflammatory Bowel Disease, Toyama University Yosuke Shimodaira Department of Gastroenterology and Neurology, Akita University Graduate School of Medicine Hisashi Shiga Division of Gastroenterology, Tohoku University Graduate School of Medicine Sakiko Hiraoka Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshihiro Inokuchi Research Center for Intestinal Health Science, Okayama University Takeshi Yamamura Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine Ryo Emoto Department of Biostatistics, Nagoya University Graduate School of Medicine Shigeyuki Matsui Department of Biostatistics, Nagoya University Graduate School of Medicine Background Small bowel (SB) lesions in Crohn’s disease (CD) are often asymptomatic despite being highly active. Fecal calprotectin (FC) is the most widely used biomarker of CD activity, but its drawbacks include a large intra-individual sample variability and the burden of collecting stool samples. Meanwhile, serum leucine-rich alpha-2 glycoprotein (LRG) has recently attracted attention as a biomarker that can address the limitations of FC. This study determined the diagnostic accuracy of LRG and its cut-off values for diagnosing CD activity in SB. Methods This was a retrospective, multi-center study of CD patients undergoing retrograde balloon-assisted endoscopy. For ileal- and ileocolonic-type patients with a colon SES-CD score of 0, we estimated the receiver operating characteristic curve of LRG and determined the cut-off value to achieve a target sensitivity level of 80%. Results Among 285 patients with SB lesions, LRG had an area under the curve (AUC) of 0.72 (95% CI 0.67–0.78) with a sensitivity of 80.2% and specificity of 47.2% for a cut-off value of 10.5 when diagnosing endoscopic remission (modified SES-CD ≤ 3), while it had an AUC of 0.72 (95% CI 0.65–0.78) with a sensitivity of 81.2% and specificity of 46.2% for a cut-off value of 10.1 when diagnosing complete ulcer healing (modified SES-CD ≤ 1). Conclusion LRG was effective for diagnosing CD activity in SB, specifically with cut-off values of 10.5 and 10.1 for endoscopic remission and complete ulcer healing, respectively. A future prospective validation study will assess its clinical utility. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Development of a micro-organic matter identifier and its application to characterise insoluble organic matter in carbonaceous chondrite and Ryugu samples EN RAHUL KUMAR Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1869-6953 16 12 2025 A Multicenter, Prospective, Observational, and Single-Arm Interventional Study of Mirogabalin in Diabetic Peripheral Neuropathic Pain: Rationale and Design of Dia-NeP 2351 2363 EN Hideki Kamiya Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine Ryo Suzuki Department of Diabetes, Metabolism and Endocrinology, Tokyo Medical University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Takahisa Deguchi Department of Diabetes, Metabolism and Endocrinology, Kagoshima University Graduate School of Medical and Dental Sciences Tatsuhito Himeno Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine Shuhei Yamamoto Data Intelligence Department, Daiichi Sankyo Co., Ltd. Taiki Toyama Primary Medical Science Department, Daiichi Sankyo Co., Ltd. Jiro Nakamura Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine Background/Objectives: The exact prevalence of and recent changes in diabetic polyneuropathy (DPN) and diabetic peripheral neuropathic pain (DPNP) in Japan are unclear. The oral gabapentinoid, mirogabalin besylate (mirogabalin), is effective with a good safety profile for DPNP with moderate-to-severe pain (numerical rating scale [NRS] scores ≥ 4). However, clinical evidence for mild pain (NRS scores ≤ 3) is unclear. The Dia-NeP study aims to examine: (1) the prevalences of DPN and DPNP and background factors in patients with type 2 diabetes mellitus (T2DM); and (2) the efficacy and safety of mirogabalin in patients with DPNP, including those with mild pain. Methods: The Dia-NeP study is a multicenter, prospective study consisting of two parts, a baseline survey and an interventional study, to be conducted from March 2025 to August 2026 in patients with T2DM in Japan. The baseline survey is the observational study investigating the epidemiology of DPN and DPNP, and the interventional study is an exploratory, single-arm, open-label study of 12-week mirogabalin treatment. Of patients with T2DM enrolled in the baseline survey, those diagnosed with DPNP who have an NRS score for pain ≥ 1 will be included in the interventional study. The target sample size is 1000 to 3000 patients for the baseline survey and 100 for the interventional study. Planned Outcomes: The primary endpoint is the change from baseline in the NRS score at week 12 in the interventional study. The safety endpoint is adverse events. This study will not only show the latest prevalence of DPN and DPNP in Japan, but is also the first study to investigate the efficacy and safety of mirogabalin in patients with DPNP having mild pain, as well as moderate-to-severe pain, and is expected to provide useful evidence for future DPN and DPNP treatment. Trial Registration: Japan Registry of Clinical Trials (jRCTs031240623, registered 20/January/2025, https://jrct.mhlw.go.jp/en-latest-detail/jRCTs031240623). No potential conflict of interest relevant to this article was reported.

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

BMJ Acta Medica Okayama 2044-6055 15 6 2025 Protocol for a multicentre, open-label, dose-escalation phase I/II study evaluating the tolerability, safety, efficacy and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with aggressive natural killer cell leukaemia e098532 EN Noriko Fukuhara Hematology, Tohoku University Graduate School of Medicine Makoto Onizuka Department of Hematology and Oncology, Tokai University School of Medicine Graduate School of Medicine Junya Kanda Department of Hematology, Graduate School of Medicine, Kyoto University Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Koji Kato Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University Kiyoshi Ando Department of Hematology, Hiroshima University Introduction Aggressive natural killer cell leukaemia (ANKL) is a rare form of NK cell lymphoma with a very low incidence and poor prognosis. While multi-agent chemotherapy including L-asparaginase has been used to treat ANKL patients, they often cannot receive adequate chemotherapy at diagnosis due to liver dysfunction. PPMX-T003, a fully human monoclonal antibody targeting the transferrin receptor 1, shows promise in treating ANKL by helping patients recover from fulminant clinical conditions, potentially enabling a transition to chemotherapy. This study aimed to evaluate the tolerability, safety, efficacy, and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with ANKL. Methods and analysis This multicentre, open-label, dose-escalation phase I/II study will be conducted at nine hospitals in Japan. Patients diagnosed with ANKL (whether as a primary or recurrent disease) and exhibiting abnormal liver function or hepatomegaly due to the primary disease will be included. The primary endpoint is the tolerability and safety of repeated continuous intravenous administration of PPMX-T003 in the first course, based on adverse events and dose-limiting toxicities. PPMX-T003 will be administered as a continuous intravenous infusion every 24 hours for five consecutive days, followed by a 2-day break. Pretreatment will be provided to minimise the risk of infusion-related reactions. Initial doses of PPMX-T003 will be 0.5, 1.0 or 2.0 mg/kg, with subsequent dose increases determined by the Data and Safety Monitoring Committee. The sample size is set at seven participants, with enrolment increased to up to 12 participants if dose-limiting toxicities occur, based on feasibility due to the rarity of ANKL. Descriptive statistics will summarise data according to initial dose, and pharmacokinetic analysis will be conducted based on administered dose. Ethics and dissemination This study was approved by the institutional review boards at participating hospitals. The results will be disseminated in peer-reviewed journals. Trial registration number jRCT2061230008 (jRCT); NCT05863234 (ClinicalTrials.gov). No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1092-9134 81 2026 The diagnostic utility and frequency of CD56 expression in plasma cell myeloma 152587 EN Midori Imai Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Tomoka Haratake Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Rio Yamada Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Syoma Kato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Mizuha Tabe Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Hiroyuki Yanai Department of Diagnostic Pathology, Okayama University Hospital Hidetaka Yamamoto Department of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Plasma cell myeloma (PCM) is a hematological malignancy characterized by systemic proliferation of neoplastic plasma cells within the bone marrow. Diagnosis requires clinical findings and immunohistochemical staining, including CD138, CD79a, cyclin D1, immunoglobulin κ (Igκ), and λ (Igλ). However, CD79a and cyclin D1 have limited sensitivity and specificity, and Igκ/Igλ assessment is often difficult due to overstaining. Therefore, more reliable antibodies are needed to accurately diagnose PCM. In this study, we examined the diagnostic utility of CD56 expression in PCM. We retrospectively performed immunostaining for CD138, CD56, CD79a, cyclin D1, Igκ, and Igλ in bone marrow samples from 116 patients with PCM. CD56 expression was observed in 85/116 cases (73.3 %), CD79a was downregulated in 46/116 cases (39.7 %), and cyclin D1 expression was observed in 42/116 cases (36.2 %). The expression of CD56 was significantly higher than that of CD79a and cyclin D1 (both p < 0.001). The combination of two antibodies resulted in the highest detection rate when combining CD56 and CD79a (105/116, 90.5 %), which was significantly higher than the detection rates of CD56 and cyclin D1 (93/116, 80.2 %) and CD79a and cyclin D1 (75/116, 64.7 %) (both p < 0.001). In contrast, lymphoplasmacytic lymphoma and marginal zone lymphoma lacked CD56 and cyclin D1 expression. Furthermore, in cases where light chain restriction was undetectable (11/116, 9.5 %), all could be diagnosed as PCM based on CD56, CD79a, and cyclin D1. Among these, CD56 showed the highest detection rate (8/11, 72.7 %). These findings highlight CD56 as a helpful marker for PCM diagnosis and support further clinical research. 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.

Springer Science and Business Media LLC Acta Medica Okayama 0007-0920 2025 Gemcitabine-induced neutrophil extracellular traps via interleukin-8-CXCR1/2 pathway promote chemoresistance in pancreatic cancer EN Shohei Nogi 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 Atsuki Taniguchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiko Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiyasu Kono Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoru Kikuchi 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 Shinji Kuroda 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 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: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, and chemoresistance poses a significant challenge in its treatment. Neutrophil extracellular traps (NETs) have emerged as key players in the tumour microenvironment, but their role in chemoresistance remains unclear. Methods: We investigated the involvement of NETs in PDAC chemoresistance using patient tumour samples, in vitro assays with gemcitabine (GEM)-treated PDAC cells, and in vivo mouse models. We evaluated cytokine production, NET formation and tumour response to GEM, with or without the CXCR1/2 inhibitor navarixin. Results: NETs are significantly accumulated in the tumours of PDAC patients exhibiting poor response to chemotherapy. GEM-treated PDAC cells secrete pro-inflammatory cytokines such as interleukin-8 (IL-8). IL-8 promote the formation of chemotherapy-induced NETs (chemoNETosis) through activation of CXCR 1/2 on neutrophils. Importantly, treatment with navarixin significantly suppressed chemoNETosis, restored sensitivity to GEM, and significantly reduced tumour growth in vivo. Conclusions: Our findings reveal that NETs contribute to chemoresistance in PDAC and that IL-8–mediated chemoNETosis plays a pivotal role in this process. Inhibition of CXCR1/2-mediated NET formation enhances the efficacy of GEM. This approach may represent a promising therapeutic strategy for overcoming chemoresistance in PDAC. These results support further clinical investigation of anti-NETs therapies. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1939-5981 2025 Effect of Repeated Gravity Casting on the Microstructure and Mechanical Properties of 6061 Aluminum Alloy EN Mitsuhiro Okayasu Department of Mechanical Systems and Engineering, Okayama University Shouei Makino Department of Mechanical Systems and Engineering, Okayama University Shota Nakagawa Research & Development Center, Marketing & Technology Division, UACJ Corporation Shuhei Takeuchi Department of Mechanical Systems and Engineering, Okayama University Yoshifumi Shinzato Research & Development Center, Marketing & Technology Division, UACJ Corporation Tadashi Minoda Research & Development Center, Marketing & Technology Division, UACJ Corporation Naotaka Ohtsuka Research & Development Center, Marketing & Technology Division, UACJ Corporation This study systematically investigates the effects of repeated gravity casting on the microstructure and mechanical properties of 6061 aluminum alloy. With an increasing number of casting cycles from one to ten, grain coarsening and a decrease in dislocation density were observed, mainly due to the significant depletion of magnesium from 1.03 to 0.01% and titanium from 0.009 to 0.005%. These microstructural changes led to a decrease in solid-solution strengthening and grain-boundary strengthening, resulting in a 30% reduction in tensile strength, while ductility increased by about three times. Moreover, work hardening decreased with increasing the casting cycle, which can be attributed not only to the microstructural changes but also to the increase in stacking fault energy (SFE) associated with compositional evolution. From the transmission electron microscopy (TEM) observations, in the 1-cycle sample, Mg2Si precipitates were finely dispersed and a high amount of Mg element in the matrix, resulting in significant dislocation accumulation, whereas the 10-cycle sample exhibited weaker dislocation tangling. These microstructural evolutions provide insight into the degradation of mechanical performance in aluminum alloys subjected to multiple casting processes. 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.

International Institute of Anticancer Research Acta Medica Okayama 1109-6535 22 6 2025 C1orf50 Accelerates Epithelial-Mesenchymal Transition and the Cell Cycle of Hepatocellular Carcinoma 836 849 EN ATSUSHI TANAKA Department of Pathology, Beth Israel Deaconess Medical Center YUSUKE OTANI Department of Pathology, Beth Israel Deaconess Medical Center MASAKI MAEKAWA Department of Pathology, Beth Israel Deaconess Medical Center ANNA ROGACHEVSKAYA Department of Pathology, Beth Israel Deaconess Medical Center TIRSO PEÑA Department of Pathology, Beth Israel Deaconess Medical Center VANESSA D. CHIN UMass Chan Medical School, UMass Memorial Medical Center SHINICHI TOYOOKA Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences MICHAEL H. ROEHRL Department of Pathology, Beth Israel Deaconess Medical Center ATSUSHI FUJIMURA Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Aim: Hepatocellular carcinoma (HCC) is a heterogeneous liver cancer with limited treatment options and a poor prognosis in advanced stages. To identify novel biomarkers and therapeutic targets, we investigated the role of chromosome 1 open reading frame 50 (C1orf50), a gene with a previously uncharacterized function in HCC. Materials and Methods: We performed a comprehensive transcriptome data analysis of the human hepatocellular carcinoma project from The Cancer Genome Atlas (TCGA) and subsequently validated the oncogenic roles of C1orf50 using HCC cell lines. Results: Using transcriptomic and clinical data from TCGA, we stratified 355 primary HCC samples based on C1orf50 expression levels. Patients with high C1orf50 expression exhibited significantly shorter overall survival, suggesting its association with aggressive tumor behavior. Differential expression and enrichment analyses revealed that C1orf50-high tumors were enriched in oncogenic pathways, including epithelial-mesenchymal transition (EMT), cell cycle activation, and stemness-related properties. Transcriptional regulatory network analysis detected 456 significantly dysregulated regulons, including ZEB1/2 and E2F2, key drivers of EMT and cell cycle, in the C1orf50-high group. In addition, we observed increased YAP1/TAZ signaling, further linking C1orf50 to stemness and therapeutic resistance. Functional data from CRISPR-based dependency screening suggested that several transcription factors up-regulated in the C1orf50-high state, such as ZBTB11 and CTCE, are essential for the survival of HCC cells. These findings indicate potential therapeutic vulnerabilities and support the rationale for targeting C1orf50-associated pathways. Conclusion: C1orf50 is a novel biomarker of poor prognosis in HCC and a key regulator of oncogenic features such as EMT, cell cycle progression, and stemness. This study highlights the therapeutic potential of targeting C1orf50-related networks in aggressive subtypes of liver cancer. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Blood Pressure and Heart Rate Patterns Identified by Unsupervised Machine Learning and Their Associations with Subclinical Cerebral and Renal Damage in a Japanese Community: The Masuda Study 369 379 EN Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Minako Kinuta Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sosuke Munetomo Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mari Fukuda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuhide Kojima Department of Radiology, Okayama University Hospital Kaori Taniguchi Department of Environmental Medicine and Public Health, Izumo, Shimane University Faculty of Medicine Noriko Nakahata Department of Health and Nutrition, The University of Shimane Faculty of Nursing and Nutrition Hideyuki Kanda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/69438 We applied unsupervised machine learning to analyze blood pressure (BP) and resting heart rate (HR) patterns measured during a 1-year period to assess their cross-sectional relationships with subclinical cerebral and renal target damage. Dimension reduction via uniform manifold approximation and projection, followed by K-means++ clustering, was used to categorize 362 community-dwelling participants (mean age, 56.2 years; 54.9% women) into three groups: Low BP and Low HR (Lo-BP/Lo-HR), High BP and High HR (Hi-BP/Hi-HR), and Low BP and High HR (Lo-BP/Hi-HR). Cerebral vessel lesions were defined as the presence of at least one of the following magnetic resonance imaging findings: lacunar infarcts, white matter hyperintensities, cerebral microbleeds, or intracranial artery stenosis. A high urinary albumin-to-creatinine ratio (UACR) was defined as the top 10% (≥ 12 mg/g) of the mean value from ≥2 measurements. Poisson regression with robust error variance, adjusted for demographics, lifestyle, and medical history, showed that the Hi-BP/Hi-HR group had relative risks of 3.62 (95% confidence interval, 1.75-7.46) for cerebral vessel lesions and 3.58 (1.33-9.67) for high UACR, and the Lo-BP/Hi-HR group had a relative risk of 3.09 (1.12-8.57) for high UACR, compared with the Lo-BP/Lo-HR group. These findings demonstrate the utility of an unsupervised, data-driven approach for identifying physiological patterns associated with subclinical target organ damage. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1347-6947 88 9 2024 Solid-state cultivation of multiple industrial strains of koji mold on different Thai unpolished rice cultivars: biotransformation of phenolic compounds and their effects on antioxidant activity 1117 1125 EN Jirayu Jitpakdee Graduate School of Environmental and Life Science, Okayama University Hideyuki Yamashita Higuchi Matsunosuke Shoten Co., Ltd. Takuro Nakagawa Higuchi Matsunosuke Shoten Co., Ltd. Teruhiko Nitoda Graduate School of Environmental and Life Science, Okayama University Hiroshi Kanzaki Graduate School of Environmental and Life Science, Okayama University Colored rice is abundant in polyphenols, and koji molds have potential for biotransformation. This study aimed to produce Thai-colored rice koji to study its polyphenolic biotransformation. Four industrial koji mold strains: Aspergillus oryzae 6001, A. oryzae 6020, A. sojae 7009, and A. luchuensis 8035, were cultivated on unpolished Thai-colored rice (Riceberry and Sangyod), unpolished Thai white rice (RD43), and polished Japanese white rice (Koshihikari). We discovered that koji molds grew on all the rice varieties. Methanol extracts of all rice kojis exhibited an approximately 2-fold or greater increase in total phenolic content and DPPH antioxidant activity compared to those of steamed rice. Moreover, quercetin, quercetin-3-O-glucoside, isorhamnetin-3-O-glucoside, ferulic acid, caffeic acid, protocatechuic acid, vanillic acid, (+)-catechin, and (–)-epicatechin content increased in Riceberry and Sangyod koji samples. Consequently, Aspergillus solid-state cultivation on unpolished Thai-colored rice exhibited higher functionalization than the cultivation of unpolished Thai white rice and polished Japanese white rice. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2624-831X 6 3 2025 An Extension of Input Setup Assistance Service Using Generative AI to Unlearned Sensors for the SEMAR IoT Application Server Platform 52 EN I Nyoman Darma Kotama Graduate School of Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Natural Science and Technology, Okayama University Yohanes Yohanie Fridelin Panduman Graduate School of Information Science and Technology, The University of Osaka Komang Candra Brata Graduate School of Natural Science and Technology, Okayama University Anak Agung Surya Pradhana Graduate School of Natural Science and Technology, Okayama University Noprianto Graduate School of Natural Science and Technology, Okayama University Nowadays, Internet of Things (IoT) application systems are broadly applied to various sectors of society for efficient management by monitoring environments using sensors, analyzing sampled data, and giving proper feedback. For their fast deployment, we have developed Smart Environmental Monitoring and Analysis in Real Time (SEMAR) as an integrated IoT application server platform and implemented the input setup assistance service using prompt engineering and a generative AI model to assist connecting sensors to SEMAR with step-by-step guidance. However, the current service cannot assist in connections of the sensors not learned by the AI model, such as newly released ones. To address this issue, in this paper, we propose an extension to the service for handling unlearned sensors by utilizing datasheets with four steps: (1) users input a PDF datasheet containing information about the sensor, (2) key specifications are extracted from the datasheet and structured into markdown format using a generative AI, (3) this data is saved to a vector database using chunking and embedding methods, and (4) the data is used in Retrieval-Augmented Generation (RAG) to provide additional context when guiding users through sensor setup. Our evaluation with five generative AI models shows that OpenAI’s GPT-4o achieves the highest accuracy in extracting specifications from PDF datasheets and the best answer relevancy (0.987), while Gemini 2.0 Flash delivers the most balanced results, with the highest overall RAGAs score (0.76). Other models produced competitive but mixed outcomes, averaging 0.74 across metrics. The step-by-step guidance function achieved a task success rate above 80%. In a course evaluation by 48 students, the system improved the student test scores, further confirming the effectiveness of our proposed extension. 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 Continuous glucose monitoring reveals periodontitis-induced glucose variability, insulin resistance, and gut microbiota dysbiosis in mice 34768 EN Moyuka Kubota-Takamori Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Omori Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chiaki Kamei-Nagata Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Fumiko Kiyama Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayuki Ishii Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaaki Nakayama Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Kimito Hirai Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Yuki Shinoda-Ito Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Okubo Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Shin Nakamura Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsushi Ikeda Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Tsugumichi Saito Department of Health & Sports Sciences, Faculty of Education, Tokyo Gakugei University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Takashiba Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Diabetes mellitus (DM) management has advanced from self-monitoring blood glucose (SMBG) to continuous glucose monitoring (CGM), which better prevents complications. However, the influence of periodontitis—a common DM complication—on glucose variability is unclear. This study examined glucose variability in mice with periodontitis using CGM. Periodontitis was induced in 9-week-old male C57BL/6J mice via silk ligatures around the upper second molars. Glucose levels were monitored over 14 days with CGM, validated by SMBG. On day 14, samples were collected to assess alveolar bone resorption and serum levels of tumor necrosis factor-α (TNF-α), insulin, and amyloid A. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were conducted to evaluate insulin resistance. Gut microbiota diversity was also analyzed. By day 10, mice with periodontitis exhibited higher mean glucose levels and time above range than controls. On day 14, serum insulin and amyloid A levels significantly increased, while TNF-α remained unchanged. GTT and ITT indicated insulin resistance. Microbiota analysis showed reduced alpha- and altered beta-diversity, with decreased Coprococcus spp. and increased Prevotella spp., linking dysbiosis to insulin resistance. Periodontitis disrupts glucose regulation by promoting insulin resistance and gut microbiota imbalance, leading to significant glucose variability. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1573-7209 28 4 2025 Cancer-associated fibroblast-derived SOD3 enhances lymphangiogenesis to drive metastasis in lung adenocarcinoma 51 EN May Wathone Oo Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takao Hikita Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoha Mashima Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kosuke Torigata School of Medicine, Kobe University Yin Min Thu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Habu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, 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 Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Sachio Ito Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hitoshi Nagatsuka Department of Thoracic Surgery, National Hospital Organization, Shikoku Cancer Center Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masanori Nakayama Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Despite advancements in diagnostic and therapeutic strategies, lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality due to its aggressive metastatic potential. Extracellular superoxide dismutase (SOD3) is an antioxidant enzyme that regulates oxidative stress and is regarded as a tumor suppressor. However, studies have demonstrated that SOD3 can either promote or inhibit cell proliferation and survival in various cancers, and its molecular mechanisms within the tumor microenvironment are poorly understood. In this study, we report a breakthrough in uncovering the role of SOD3 derived from cancer-associated fibroblasts (CAFs) in LUAD. Using LUAD xenograft models co-implanted with SOD3-overexpressing CAFs (CAFSOD3), we observe an aggressive tumor phenotype characterized by increased lymphangiogenesis and lymphatic vessel invasion (LVI) of the tumor. Additionally, LUAD patients with elevated SOD3 levels exhibit a higher incidence of LVI and metastasis. Notably, RNA sequencing of CAFSOD3 reveals that SOD3-mediated VEGF-dependent tumor progression and lymphangiogenesis are up-regulated. Furthermore, single-cell transcriptomic analysis of LUAD clinical samples confirms a strong correlation between SOD3 expression in fibroblasts and characteristics of tumor exacerbation, such as lymphangiogenesis and metastasis. These findings underscore new insights into the role of CAF-derived SOD3 in LUAD progression and highlight its potential as a biomarker and therapeutic target. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2590-1974 27 2025 Development of a technique to identify μm-sized organic matter in asteroidal material: An approach using machine learning 100277 EN Rahul Kumar The Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Katsura Kobayashi The Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Christian Potiszil The Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Tak Kunihiro The Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Asteroidal materials contain organic matter (OM), which records a number of extraterrestrial environments and thus provides a record of Solar System processes. OM contain essential compounds for the origin of life. To understand the origin and evolution of OM, systematic identification and detailed observation using in-situ techniques is required. While both nm- and μm-sized OM were studied previously, only a small portion of a given sample surface was investigated in each study. Here, a novel workflow was developed and applied to identify and classify μm-sized OM on mm-sized asteroidal materials. The workflow involved image processing and machine learning, enabling a comprehensive and non-biased way of identifying, classifying, and measuring the properties of OM. We found that identifying OM is more accurate by classification with machine learning than by clustering. On the approach of classification with machine learning, five algorithms were tested. The random forest algorithm was selected as it scored the highest in 4 out of 5 accuracy parameters during evaluation. The workflow gave modal OM abundances that were consistent with those identified manually, demonstrating that the workflow can accurately identify 1-15 μm-sized OM. The size distribution of OM was modeled using the power-law distribution, giving slope α values that were consistent with fragmentation processes. The shape of the OM was quantified using circularity and solidity, giving a positive correlation and indicating these properties are closely related. Overall, the workflow enabled identification of many OM quickly and accurately and the obtainment of chemical and petrographic information. Such information can help the selection of OM for further in-situ techniques, and elucidate the origin and evolution of OM preserved in asteroidal materials. No potential conflict of interest relevant to this article was reported.

Ceramic Society of Japan Acta Medica Okayama 1348-6535 133 1 2025 Comparative study of the effects of fluoride treatment with cyclic variations in pH on the structures of stoichiometric, calcium-deficient, and carbonated hydroxyapatites 15 24 EN Satoshi Hayakawa Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yu Okada Graduate School of Natural Science and Technology, Okayama University Tomohiko Yoshioka Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University The primary objective of this study was to analyze the effects of fluoride treatment with cyclic variations in pH on the structure of stoichiometric hydroxyapatite (HAp), calcium-deficient HAp (CDHAp), and carbonated HAp (CHAp) powders. The structures of HAp, CDHAp, and CHAp before and after fluoride treatment were investigated using X-ray diffraction, Fourier-transform infrared, Raman, and nuclear magnetic resonance spectroscopic analyses. The fluoride treatment with cyclic variations in pH increased the calcium deficiency in HAp and CHAp but decreased in CDHAp. During fluoride treatment, fluoridated CDHAp or fluoridated calcium-deficient CHAp was formed on the surface of the HAp samples via dissolution and crystal growth, accompanied by the selective elution of component ions and partial substitution of OH− groups in the HAp hexagonal lattice with F− ions. No evidence of the formation of Ca(OH)2 and OH− groups outside the HAp crystal lattice was obtained. A new perspective on the formation of structured water at the surface termination of the OH columns (disordered region), with possible interactions with adsorbed water molecules or nonspecifically adsorbed F− ions was provided. The top surface of the fluoridated CDHAp consisted of an amorphous fluoride-rich hydrated layer, which included calcium phosphate and CaF2. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 26 17 2025 Anti-HMGB1 Antibody Therapy Ameliorates Spinal Cord Ischemia–Reperfusion Injury in Rabbits 8643 EN Genya Muraoka Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Fujii Department of Translational Research, Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Keyue Liu Department of Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Handong Qiao Department of Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Dengli Wang Department of Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daiki Ousaka Department of Medical Technology, Faculty of Science, Okayama University of Science Susumu Oozawa Division of Medical Safety Management, Safety Management Facility, Okayama University Hospital Shingo Kasahara Department of Cardiovascular Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiro Nishibori Department of Translational Research and Drug Development, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Spinal cord ischemia–reperfusion (SCI/R) injury remains a major clinical challenge with limited therapeutic options. High-mobility group box 1 (HMGB1), a proinflammatory mediator released during cellular stress, has been implicated in the pathogenesis of ischemia–reperfusion-induced neural damage. In this study, we investigated the neuroprotective potential of the anti-HMGB1 monoclonal antibody (mAb) in a rabbit model of SCI/R injury. Male New Zealand White rabbits were anesthetized and subjected to 11 min of abdominal aortic occlusion using a micro-bulldog clamp following heparinization. Anti-HMGB1 mAb or control IgG was administered intravenously immediately after reperfusion and again at 6 h post-reperfusion. Neurological function was assessed at 6, 24, and 48 h after reperfusion using the modified Tarlov scoring system. The rabbits were euthanized 48 h after reperfusion for spinal cord and blood sampling. Treatment with anti-HMGB1 mAb significantly improved neurological outcomes, reduced the extent of spinal cord infarction, preserved motor neuron viability, and decreased the presence of activated microglia and infiltrating neutrophils. Furthermore, it attenuated apoptosis, oxidative stress, and inflammatory responses in the spinal cord, and helped maintain the integrity of the blood–spinal cord barrier. These findings suggest that anti-HMGB1 mAb may serve as a promising therapeutic agent for SCI/R injury. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1071-2690 2025 S100A8/A9-MCAM signaling promotes gastric cancer cell progression via ERK-c-Jun activation EN Youyi Chen Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine Xu Yang Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine Rie Kinoshita Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nahoko Tomonobu Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Bo Pan The First Affiliated Hospital, Zhejiang University School of Medicine Fangping Wu School of Pharmaceutical Sciences, Zhejiang Chinese Medical University Xu Zhang Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine Kazumi Sagayama Faculties of Educational and Research Management Field, Okayama University Bei Sun Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences S100 protein family members S100A8 and S100A9 function primarily as a heterodimer complex (S100A8/A9) in vivo. This complex has been implicated in various cancers, including gastric cancer (GC). Recent studies suggest that these proteins play significant roles in tumor progression, inflammation, and metastasis. However, the exact mechanisms by which S100A8/A9 contributes to GC pathogenesis remain unclear. This study investigates the role of S100A8/A9 and its receptor in GC. Immunohistochemical analysis was performed on GC tissue samples to assess the expression of the S100A8/A9 receptor melanoma cell adhesion molecule (MCAM). In vitro transwell migration and invasion assays were used to evaluate the motility and invasiveness of GC cells. Cell proliferation was assessed using a growth assay, and Western blotting (WB) was employed to examine downstream signaling pathways, including ERK and the transcription factor c-Jun, in response to S100A8/A9–MCAM interaction. S100A8/A9 stimulation enhanced both proliferation and migration through MCAM binding in GC cell lines. These cellular events were accompanied by ERK activation and c-Jun induction. Downregulation of MCAM suppressed both ERK phosphorylation and c-Jun expression, highlighting the importance of the S100A8/A9‒MCAM‒ERK‒c-Jun axis in promoting GC progression. These findings indicate that S100A8/A9 contributes to GC progression via MCAM, which activates the ERK‒c-Jun pathway. The S100A8/A9‒signaling axis may represent a novel therapeutic target in GC. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 14 17 2025 Evaluation of the Diagnostic Performance of the Brush/Biopsy Rapid On-Site Evaluation (B-ROSE) in Cases of Bile Duct Stricture: A Prospective, Pilot Study 6207 EN Nao Hattori Department of Gastroenterology, Okayama University Hospital Daisuke Uchida Department of Gastroenterology, Okayama University Hospital Kei Harada Department of Gastroenterology, Okayama University Hospital Ryosuke Sato Department of Gastroenterology, Okayama University Hospital Taisuke Obata Department of Gastroenterology, Okayama University Hospital Akihiro Matsumi Department of Gastroenterology, Okayama University Hospital Kazuya Miyamoto Department of Gastroenterology, Okayama University Hospital Hiroyuki Terasawa Department of Gastroenterology, Okayama University Hospital Yuki Fujii Department of Gastroenterology, Okayama University Hospital Koichiro Tsutsumi Department of Gastroenterology, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology, Okayama University Hospital settingsOrder Article Reprints Open AccessArticle Evaluation of the Diagnostic Performance of the Brush/Biopsy Rapid On-Site Evaluation (B-ROSE) in Cases of Bile Duct Stricture: A Prospective, Pilot Study by Nao Hattori 1,Daisuke Uchida 1,2,*,Kei Harada 1,Ryosuke Sato 1ORCID,Taisuke Obata 1,Akihiro Matsumi 1ORCID,Kazuya Miyamoto 1ORCID,Hiroyuki Terasawa 1ORCID,Yuki Fujii 1,Koichiro Tsutsumi 1ORCID,Shigeru Horiguchi 1,Kazuyuki Matsumoto 1ORCID andMotoyuki Otsuka 1 1 Department of Gastroenterology, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan 2 Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan * Author to whom correspondence should be addressed. J. Clin. Med. 2025, 14(17), 6207; https://doi.org/10.3390/jcm14176207 Submission received: 23 June 2025 / Revised: 21 August 2025 / Accepted: 26 August 2025 / Published: 2 September 2025 (This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine) Downloadkeyboard_arrow_down Browse Figures Versions Notes Abstract Background: Biliary strictures are diagnosed using endoscopic retrograde cholangiopancreatography (ERCP) with brush cytology and biopsy. However, brush cytology shows a sensitivity of 9–56.1% and a diagnostic accuracy of 43–65.4%, while biopsy demonstrates a sensitivity of 48%. Both methods exhibit high specificity but limited sensitivity. While rapid on-site evaluation (ROSE) is effective in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), its application in ERCP-obtained samples remains underexplored. Methods: This prospective pilot study was conducted at Okayama University Hospital from April 2019 to July 2024. Patients requiring ERCP-guided sampling for bile duct strictures were included. ROSE was applied to brush cytology with up to three additional attempts and to imprint cytology from biopsy samples with up to two attempts. Diagnostic accuracy was assessed based on pathology and clinical course. Results: Among 37 patients (median age: 73 years, add range, and male–female ratio: 27:10), 18 had hilar and 19 had distal bile duct strictures. Brush cytology required one, two, or three attempts in twenty-six, six, and five cases, respectively, whereas biopsy required one or two attempts in thirty-five and two cases, respectively. Among the thirty-seven cases, thirty-five were malignant and two were benign. The B-ROSE group showed a sensitivity, specificity, and accuracy of 71.4%, 100.0%, and 73.0%, respectively, compared to lower accuracy in the conventional group, where single brush cytology attempts yielded a sensitivity of 48.6% and an accuracy of 48.6%, and single biopsy attempts showed a sensitivity of 68.6% and an accuracy of 70.3%. Conclusions: B-ROSE improves diagnostic accuracy, reduces repeat sampling, and minimizes patient burden in ERCP-based diagnosis of bile duct strictures, making it a valuable addition to current diagnostic protocols. No potential conflict of interest relevant to this article was reported.

International Union of Crystallography (IUCr) Acta Medica Okayama 1600-5775 32 5 2025 X-ray fluorescence holography under high-pressure conditions 1302 1309 EN Xinhui Zhan Graduate School of Advanced Science and Engineering, Hiroshima University Naoki Ishimatsu Geodynamics Research Center, PIAS, Ehime University Koji Kimura Department of Physical Science and Engineering, Nagoya Institute of Technology Naohisa Happo Graduate School of Information Sciences, Hiroshima City University Halubai Sekhar Institute of Industrial Nanomaterials, Kumamoto University Tomoko Sato Institute of Materials Structure Science, High Energy Accelerator Research Organization, KEK Nobuo Nakajima Graduate School of Advanced Science and Engineering, Hiroshima University Naomi Kawamura Japan Synchrotron Radiation Research Institute, SPring-8 Kotaro Higashi Japan Synchrotron Radiation Research Institute, SPring-8 Oki Sekizawa Japan Synchrotron Radiation Research Institute, SPring-8 Hirokazu Kadobayashi Japan Synchrotron Radiation Research Institute, SPring-8 Ritsuko Eguchi Graduate School of Science, University of Hyogo Yoshihiro Kubozono Research Institute for Interdisciplinary Science, Okayama University Hiroo Tajiri Japan Synchrotron Radiation Research Institute, SPring-8 Shinya Hosokawa Faculty of Materials for Energy, Shimane University Tomohiro Matsushita Graduate School of Science and Technology, Nara Institute of Science and Technology Toru Shinmei Geodynamics Research Center, PIAS, Ehime University Tetsuo Irifune Geodynamics Research Center, PIAS, Ehime University Koichi Hayashi Department of Physical Science and Engineering, Nagoya Institute of Technology This study reports the first application of X-ray fluorescence holography (XFH) under high-pressure conditions. We integrated XFH with a diamond anvil cell to investigate the local structure around Sr atoms in single-crystal SrTiO3 under high pressure. By utilizing nano-polycrystalline diamond anvils and a yttrium filter, we effectively eliminated significant background noise from both the anvils and the gasket. This optimized experimental configuration enabled the measurement of Sr Kα holograms of the SrTiO3 sample at pressures up to 13.3 GPa. The variation of lattice constants with pressure was calculated by the shifts of Kossel lines, and real-space images of the atomic structures were reconstructed from the Sr Kα holograms at different pressures. This work successfully demonstrates the feasibility of employing XFH under high-pressure conditions as a novel method for visualizing pressure-induced changes in the three-dimensional local structure around the specified element. No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Coronary cross-sectional area stenosis severity determined using coronary CT highly correlated with coronary functional flow reserve: a pilot study 26737 EN Takuto Koumoto Division of Radiation, Okayama Heart Clinic Shozo Kusachi Okayama University Graduate School of Health Sciences Takumi Tomiya Division of Cardiovascular Intervention, Okayama Heart Clinic Takuya Akagi Division of Cardiovascular Intervention, Okayama Heart Clinic Hiroshi Kawamura Division of Cardiovascular Medicine, Okayama Heart Clinic Satoshi Hirohata Okayama University Graduate School of Health Sciences Hirosuke Yamaji Division of Cardiovascular Medicine, Okayama Heart Clinic Takashi Murakami Division of Cardiovascular Medicine, Okayama Heart Clinic Shigeshi Kamikawa Division of Cardiovascular Intervention, Okayama Heart Clinic Masaaki Murakami Division of Cardiovascular Intervention, Okayama Heart Clinic Fractional flow reserve (FFR) is the gold standard for assessing the physiological significance of coronary stenosis. We examined the potential correlation between digitally measured coronary cross-sectional area stenosis using coronary computed tomography (CT) angiography and FFR. We analyzed data of 32 consecutive patients with stenoses who underwent invasive FFR determination. The cross-sectional area was assessed using 128-slice coronary detector-based spectral CT angiography. Power analysis revealed that the sample size enabled the detection of an area under the receiver operating characteristic (ROC) curve (AUC) of 0.90. FFR ≤ 0.8 and > 0.8 were defined as FFR-positive and FFR-negative, respectively. Intra- and interobserver differences were negligible. Percentage cross-sectional area stenosis was calculated as 100 × (A−B)/A, where A is the cross-sectional area at non-stenotic pre-stenotic segment and B is the cross-sectional area of the most severe stenotic lesion. AUC indicated that percentage cross-sectional area stenosis effectively discriminated between FFR-positive and FFR-negative cases, yielding a sensitivity of 0.882 and specificity of 0.933 at a cutoff of 50% area reduction, with an AUC of 0.976. Lesions with less than 45% cross-sectional area stenosis on coronary CT angiography were not FFR-positive. When ROC analysis was conducted for lesion characteristics, AUC did not significantly improve. In conclusion, the percent coronary cross-sectional area stenosis measured using coronary CT angiography distinguished between FFR-positive and FFR-negative lesions with high accuracy. The severity of coronary cross-sectional area stenosis determined using CT angiography is clinically useful for predicting FFR. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2053-3624 12 1 2025 Clinical impact of combined assessment of myocardial inflammation and fibrosis using myocardial biopsy in patients with dilated cardiomyopathy: a multicentre, retrospective cohort study e003250 EN Takafumi Nakayama Department of Cardiology, Nagoya City University Graduate School of Medical Sciences Keiko Ohta Ogo Department of Pathology, National Cerebral and Cardiovascular Center Yasuo Sugano Department of Cardiology, Keiyu Hospital Tetsuro Yokokawa Department of Cardiovascular Medicine, Fukushima Medical University Hiromitsu Kanamori Department of Cardiology, Gifu University Graduate School of Medicine Yoshihiko Ikeda Department of Pathology, National Cerebral and Cardiovascular Center Michiaki Hiroe Department of Cardiology, National Center for Global Health and Medicine Kinta Hatakeyama Department of Pathology, National Cerebral and Cardiovascular Center Hatsue Ishibashi-Ueda Department of Pathology, National Cerebral and Cardiovascular Center Kazufumi Nakamura Center for Advanced Heart Failure, Okayama University Hospital Kaoru Dohi Department of Cardiology and Nephrology, Mie University Graduate School of Medicine Toshihisa Anzai Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine Yoshihiro Seo Department of Cardiology, Nagoya City University Graduate School of Medical Sciences Kyoko Imanaka-Yoshida Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine Background Among patients with dilated cardiomyopathy (DCM), myocardial inflammation and fibrosis are risk factors for poor clinical outcomes. Here, we investigated the combined prognostic value of these two factors, as evaluated using myocardial biopsy samples. Methods This retrospective and multicentre study included patients with DCM—defined as LVEF of ≤45% and left diastolic diameter of >112% of predicted value, without evidence of secondary or ischaemic cardiomyopathy. In myocardial biopsy samples, inflammatory cells were counted using immunohistochemistry, and Masson’s Trichrome staining was performed to quantify the myocardial fibrosis as collagen area fraction (CAF). Higher myocardial inflammation was defined as leucocytes of ≥14/mm², including ≤4 monocytes/mm², with CD3+ T lymphocytes of≥7/mm². Greater myocardial fibrosis was defined as CAF of>5.9% by the Youden’s index. The primary endpoint was cardiac death or left ventricular assist device implantation. Results A total of 255 DCM patients were enrolled (average age, 53.1 years; 78% males). Within this cohort, the mean LVEF was 28.0%, mean CAF was 10.7% and median CD3+ cell count was 8.3/mm2. During the median follow-up period of 2688 days, 46 patients met the primary endpoint. Multivariable Cox proportional hazard analyses revealed that CD3+ cell count and CAF were independent determinants of the primary endpoint. Kaplan–Meier analysis showed that patients with both higher myocardial inflammation and greater fibrosis had the worst prognosis (log-rank p<0.001). When myocardial inflammation was graded as one of three degrees: T lymphocytes of <13/mm² (low); 13 of 13.1–23.9/mm² (moderate); and T lymphocytes of ≥24 /mm² (high), patients with moderate inflammation exhibited a superior survival rate when CAF was ≤5.9%, but a worse survival rate when CAF was >5.9%. Conclusions Having both biopsy-proven higher myocardial inflammation and greater fibrosis predicted the worst clinical prognosis in patients with DCM. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1598-2351 2025 Hydrogen Embrittlement Characteristics of Austenitic Stainless Steels After Punching Process EN Mitsuhiro Okayasu Department of Mechanical and Systems Engineering, Okayama University Xichang Li Department of Mechanical and Systems Engineering, Okayama University Tomohisa Kawakami SHOYO SANGYO Co., Ltd. This study investigates the influence of microstructural characteristics on the hydrogen embrittlement of SUS304 austenitic stainless steel. The investigation utilized SUS304 sheets with a thickness of 1.5 mm, which were processed by punching with an 8 mm diameter to make specimens. Severe plastic deformation was localized near the punching edge, with the extent of deformation determined by the punching speed. Slower punching speeds induced more pronounced plastic strain, which was closely associated with work hardening and strain-induced martensitic (SIM) transformation. The SIM phase was predominantly observed within a depth of approximately 0.1 mm from the punched edge when processed at a punching speed of 0.25 mm/s, corresponding to roughly 10% of the cross-sectional area of the sample. These microstructural changes led to a significant reduction in tensile and fatigue strength, thereby exacerbating susceptibility to severe hydrogen embrittlement, despite the limited extent of microstructural alteration. Based on these findings, a modified Goodman diagram for SUS304 austenitic stainless steel, incorporating mechanical properties and hydrogen embrittlement behavior, was proposed. 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 0969-806X 239 2026 Counting-loss correction procedure of X-ray imaging detectors with consideration for the effective atomic number of biological objects 113237 EN Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Daiki Kobayashi Graduate School of Medical Sciences, Kanazawa University Tatsuya Maeda Graduate School of Medical Sciences, Kanazawa University Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Sota Goto Faculty of Health Science, Kobe Tokiwa University Yuki Kanazawa Faculty of Life Science, Kumamoto University Akitoshi Katsumata Oral Radiology and Artificial Intelligence, Asahi University Shuichiro Yamamoto JOB CORPORATION Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University It is necessary to correct counting loss caused by the pulse pile-up effect and dead time when using energy-resolving photon-counting detectors (ERPCDs) under “high-counting-rate” conditions in medical and/or industrial settings. We aimed to develop a novel counting-loss correction procedure in which biological objects having effective atomic numbers (Zeff values) of 6.5–13.0 are measured with polychromatic X-rays. To correct for counting loss, such a procedure must theoretically estimate the count value of an ideal X-ray spectrum without counting loss. In this study, we estimated the ideal X-ray spectrum by focusing on the following two points: (1) the X-ray attenuation in an object (Zeff values of 6.5–13.0) and (2) the detector response. Virtual materials having intermediate atomic numbers between 6.5 and 13.0 were generated by using a mixture of polymethylmethacrylate (PMMA, Zeff = 6.5) and aluminum (Al, Zeff = 13.0). We then constructed an algorithm that can perform the counting-loss correction based on the object’s true Zeff value. To demonstrate the applicability of our procedure, we analyzed investigational objects consisting of PMMA and Al using a prototype ERPCD system. A fresh fish sample was also analyzed. The Zeff values agree with the theoretical values within an accuracy of Zeff ±1. In conclusion, we have developed a highly accurate procedure for correcting counting losses for the quantitative X-ray imaging of biological objects. No potential conflict of interest relevant to this article was reported.

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

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

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.

Springer Science and Business Media LLC Acta Medica Okayama 1939-5981 2025 Study of the Mechanical Properties of Al–Mg ADC6 Aluminum Alloy Produced by Unidirectional Casting Under Various Cooling Rates EN S. Takeuchi M. Okayasu To create the high strength and high ductility of Al–Mg-based aluminum alloy (JIS–ADC6), ADC6 samples were produced by the unidirectional continuous casting (HMC). The HMC process was conducted with direct water cooling to melt ADC6, which can make fine microstructures and control crystal orientation. The cast samples were prepared under various cooling rates (CRs): 6.3, 34, and 62 K/s. The microstructure and crystal orientation of the samples were altered with CR. At CRs of 34 K/s and 62 K/s, the α-Al phases and intermetallic compounds, e.g., Mg2Si and Al15(Fe, Mn)3Si2, became finer and more spherical. The secondary dendrite arm spacing for the sample at 62 K/s was 8.7 µm—more than 70% smaller than the ADC6 sample (ingot) made by a gravity casting process. Notably, at a CR of 34 K/s, the crystal orientation was predominantly arranged with the (101) plane. Tensile properties—ultimate tensile strength (σUTS), 0.2% proof stress (σ0.2), and failure strain (εf)—varied with the CR. The tensile strength (σUTS and σ0.2) consistently increased with increasing the CR. The improvement in the tensile strength resulted from the refined microstructures, such as the α-Al phase and intermetallic compounds. Similarly, the failure strain also increased with increasing CR, which was severely affected by the finer and more spherical intermetallic compounds. In this case, the εf value of the sample at 34 K/s was, however, slightly higher than that at 62 K/s, due to more uniformly organized crystal orientation, while their ductility was much higher than that of the gravity cast sample. The tensile properties in detail were further analyzed using their failure characteristics. No potential conflict of interest relevant to this article was reported.

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

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

MDPI AG Acta Medica Okayama 2076-3417 15 11 2025 Top-Down Stereolithography-Based System for Additive Manufacturing of Zirconia for Dental Applications 6155 EN Kumiko Yoshihara National Institute of Advanced Industrial Science and Technology (AIST), Health and Medical Research Institute Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Fiona Spirrett Joining and Welding Research Institute, Osaka University Yukinori Maruo Department of Prosthodontics, Okayama University Yasuhiro Yoshida Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Bart Van Meerbeek BIOMAT, Department of Oral Health Sciences, KU Leuven Soshu Kirihara Joining and Welding Research Institute, Osaka University This study investigated the feasibility and effectiveness of a commercial top-down stereolithography (SLA)-based system for the additive manufacturing of zirconia dental prostheses. Yttria-stabilized zirconia–resin slurries were prepared, and zirconia objects were fabricated using a top-down SLA system. Thermogravimetric–differential thermal analysis was used to examine the resin, while X-ray fluorescence spectroscopy and X-ray diffraction were used to analyze the printed samples. The microstructures of additively manufactured and subtractively manufactured zirconia were compared using field emission scanning electron microscopy (FE-SEM) before and after sintering. Biaxial flexural strength tests were also conducted to evaluate mechanical properties. The green bodies obtained via additive manufacturing exhibited uniform layering with strong interlayer adhesion. After sintering, the structures were dense with minimal porosity. However, compared to subtractively manufactured zirconia, the additively manufactured specimens showed slightly higher porosity and lower biaxial flexural strength. The results demonstrate the potential of SLA-based additive manufacturing for dental zirconia applications while also highlighting its current mechanical limitations. The study also showed that using a blade to evenly spread viscous slurry layers in a top-down SLA system can effectively reduce oxygen inhibition at the surface and relieve internal stresses during the layer-by-layer printing process, offering a promising direction for clinical adaptation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2431 24 1 2024 Body weight and eating attitudes influence improvement of depressive symptoms in children and pre-adolescents with eating disorders: a prospective multicenter cohort study 551 EN Yuichi Suzuki Department of Pediatrics, Fukushima Medical University School of Medicine Shinichiro Nagamitsu Department of Pediatrics, Fukuoka University Faculty of Medicine Nobuoki Eshima Department of Pediatrics, Kurume University School of Medicine Takeshi Inoue Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center Ryoko Otani Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center Ryoichi Sakuta Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center Toshiyuki Iguchi Department of Pediatrics, Hoshigaoka Maternity Hospital Ryuta Ishii Department of Pediatrics and Child Health, Kurume University School of Medicine Soh Uchida Karamun`S Forest Children`S Clinic Ayumi Okada Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kitayama Himeji City Center for the Disabled Kenshi Koyanagi Nagasaki Prefectural Center of Medicine and Welfare for Children Yuki Suzuki Department of Pediatrics, National Hospital Organization Mie National Hospital Yoshino Sumi Mental and Developmental Clinic for Children “Elm Tree” Shizuo Takamiya Takamiya Psychiatry Clinic Chikako Fujii Department of Pediatrics/Child Psychosomatic Medicine, Okayama University Hospital Yoshimitsu Fukai Department of Pediatrics, St. Luke’s International Hospital Background Pediatric patients with eating disorders in a multicenter joint study on 11 facilities were enrolled and prospectively investigated to determine whether improvement in body weight, eating attitudes, and psychosocial factors in children with eating disorders would also improve depressive symptoms. Methods In this study, 91 patients were enrolled between April 2014 and March 2016. The severity of underweight was assessed using the body mass index-standard deviation score (BMI-SDS), eating behavior was assessed using the children's eating attitude test (ChEAT26), the outcome of childhood eating disorders was assessed using the childhood eating disorder outcome scale, and depressive symptoms were assessed using the Children's Depression Inventory (CDI) score. Results After 12 months of treatment, depressive symptoms were evaluated in 62 of the 91 cases where it was evaluated at the initial phase. There was no difference in background characteristics between the included patients and the 29 patients who dropped out. A paired-sample t-test revealed a significant decrease in CDI scores after 12 months of treatment (p < 0.001, 95% CI: 2.401–7.373) and a significant increase in the BMI-SDS (p < 0.001, 95% CI: − 2.41973–1.45321). Multiple regression analysis revealed that BMI-SDS and ChEAT26 scores at the initial phase were beneficial in CDI recovery. In addition, BMI-SDS at the initial phase was useful for predicting BMI-SDS recovery after 12 months of treatment. Conclusions Depressive symptoms in children with eating disorders improved with therapeutic intervention on body weight and eating attitudes. Trial registration The Clinical Trial Number for this study is UMIN000055004. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2052-7276 11 11 2024 A low-cost dpMIG-seq method for elucidating complex inheritance in polysomic crops: a case study in tetraploid blueberry uhae248 EN Kyoka Nagasaka Graduate School of Agriculture, Kyoto University Kazusa Nishimura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ko Motoki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Keigo Yamagata Graduate School of Agriculture, Kyoto University Soichiro Nishiyama Graduate School of Agriculture, Kyoto University Hisayo Yamane Graduate School of Agriculture, Kyoto University Ryutaro Tao Graduate School of Agriculture, Kyoto University Ryohei Nakano Graduate School of Agriculture, Kyoto University Tetsuya Nakazaki Graduate School of Agriculture, Kyoto University Next-generation sequencing (NGS) library construction often requires high-quality DNA extraction, precise adjustment of DNA concentration, and restriction enzyme digestion to reduce genome complexity, which results in increased time and cost in sample preparation and processing. To address these challenges, a PCR-based method for rapid NGS library preparation, named dpMIG-seq, has been developed and proven effective for high-throughput genotyping. However, the application of dpMIG-seq has been limited to diploid and polyploid species with disomic inheritance. In this study, we obtained genome-wide single nucleotide polymorphism (SNP) markers for tetraploid blueberry to evaluate genotyping and downstream analysis outcomes. Comparison of genotyping qualities inferred across samples with different DNA concentrations and multiple bioinformatics approaches revealed high accuracy and reproducibility of dpMIG-seq-based genotyping, with Pearson's correlation coefficients between replicates in the range of 0.91 to 0.98. Furthermore, we demonstrated that dpMIG-seq enables accurate genotyping of samples with low DNA concentrations. Subsequently, we applied dpMIG-seq to a tetraploid F1 population to examine the inheritance probability of parental alleles. Pairing configuration analysis supported the random meiotic pairing of homologous chromosomes on a genome-wide level. On the other hand, preferential pairing was observed on chr-11, suggesting that there may be an exception to the random pairing. Genotypic data suggested quadrivalent formation within the population, although the frequency of quadrivalent formation varied by chromosome and cultivar. Collectively, the results confirmed applicability of dpMIG-seq for allele dosage genotyping and are expected to catalyze the adoption of this cost-effective and rapid genotyping technology in polyploid studies. No potential conflict of interest relevant to this article was reported.

岡山大学経済学会 Acta Medica Okayama 2433-4146 57 1 2025 イノベーションの発生源研究の再検討 1 20 EN Qi Huang Daiji Fujii 10.18926/OER/69001 　本論文は，イノベーションの発生源に関する先行研究を振り返り，「いつ」「どこで」「誰によって」イノベーションが生み出されるのかを理論的に考察することを目的とする。考察の結果，「B to B」の文脈においては，イノベーションの発生源が企業ユーザーへ移行するメカニズムとして，取引コスト理論，期待利益仮説，情報粘着性の仮説，企業内部の独自能力（吸収能力），および外部の産業構造（製品アーキテクチャ・エコシステム）といった複数の要素からなる経済的合理性の観点から分析されていることが明らかになった。一方，「B to C」の文脈では，エンドユーザーがイノベーションに向かう動機として，「ニッチ市場に対するメーカーの消極的な対応」「創造的活動の楽しさ」「ユーザーコミュニティとの繋がり」「知識・スキルの向上」など多種多様な要素が存在し，中でも創造的活動の楽しさが根源的な動機づけの1つであると確認された。一方で，イノベーターを突き動かす心理的要因をブラックボックス化したまま放置することは，単なる知的好奇心の問題に留まらず，社会科学としての経営学にとっても重要な問題であると考えられる。今後のイノベーションの発生源研究においては，起業家をはじめとするイノベーター個人の心理的側面にいかに目を向け，創造的活動におけるポジティブな感情が働くメカニズムをイノベーションの発生メカニズムにいかに位置づけるか，その研究アプローチの提示が求められる。 No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0168-1702 351 2025 Evidence for the replication of a plant rhabdovirus in its arthropod mite vector 199522 EN Hideki Kondo Institute of Plant Science and Resources (IPSR), Okayama University Miki Fujita Institute of Plant Science and Resources (IPSR), Okayama University Paul Telengech Institute of Plant Science and Resources (IPSR), Okayama University Kazuyuki Maruyam Institute of Plant Science and Resources (IPSR), Okayama University Kiwamu Hyodo Institute of Plant Science and Resources (IPSR), Okayama University Aline Daniele Tassi Tropical Research and Education Center, University of Florida Ronald Ochoa Systematic Entomology Laboratory, USDA Ida Bagus Andika College of Plant Protection, Northwest A&F University Nobuhiro Suzuki Institute of Plant Science and Resources (IPSR), Okayama University Transmission of plant viruses that replicate in the insect vector is known as persistent-propagative manner. However, it remains unclear whether such virus-vector relationships also occur between plant viruses and other biological vectors such as arthropod mites. In this study, we investigated the possible replication of orchid fleck virus (OFV), a segmented plant rhabdovirus, within its mite vector (Brevipalpus californicus s.l.) using quantitative RT-qPCR, western blotting and next-generation sequencing. Time-course RT-qPCR and western blot analyses showed an increasing OFV accumulation pattern in mites after virus acquisition. Since OFV genome expression requires the transcription of polyadenylated mRNAs, polyadenylated RNA fractions extracted from the viruliferous mite samples and OFV-infected plant leaves were used for RNA-seq analysis. In the mite and plant datasets, a large number of sequence reads were aligned to genomic regions of OFV RNA1 and RNA2 corresponding to transcribed viral gene mRNAs. This includes the short polyadenylated transcripts originating from the leader and trailer regions at the ends of the viral genome, which are believed to play a crucial role in viral transcription/replication. In contrast, a low number of reads were mapped to the non-transcribed regions (gene junctions). These results strongly suggested that OFV gene expression occurs both in mites and plants. Additionally, deep sequencing revealed the accumulation of OFV-derived small RNAs in mites, although their size profiles differ from those found in plants. Taken together, our results indicated that OFV replicates within a mite vector and is targeted by the RNA-silencing mechanism. No potential conflict of interest relevant to this article was reported.

African Journals Online (AJOL) Acta Medica Okayama 1726-801X 39 8 2025 Chemical composition of essential oil of Acacia crassicarpa Benth. (Fabaceae) from Vietnam 1653 1660 EN Tuan Quoc Doan Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tai Tien Dinh Hue Union of Science and Technology Associations (HUSTA) Tetsuya K. Matsumoto Graduate School of Science and Engineering, Ibaraki University Dien Dinh Phong Dien Nature Reserve, Phong Dien district, Thua Thien Hue province Naoko Miki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Muneto Hirobe Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hoai Thi Nguyen Faculty of Pharmacy, Hue University of Medicine and Pharmacy, Hue University This research aimed to identify the volatile compounds found in the fresh leaves of Acacia crassicarpa Benth. This is the first phytochemical investigation of this species. Essential oils from the leaves of A. crassicarpa were obtained by hydro-distillation and analyzed by gas chromatography coupled with mass spectrometry (GC/MS). Sixty-one compounds accounting for 95.8% of the leaf oil were identified. The classes of compounds identified in the oil sample were aldehydes (30.7%), sesquiterpene hydrocarbons (25.2%), alkanes (19.1%), oxygenated monoterpenes (3.6%) oxygenated sesquiterpenes (2.3%), monoterpene hydrocarbons (0.8%) and others (14.2%). The major constituents in the leaf oil were tridecanal (24.5%), (E)-caryophyllene (11.7%), n-heneicosane (7.2%), squalene (6.5%), and 7-tetradecenal (5.9%). No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0012-821X 653 2025 Meteoritic and asteroidal amino acid heterogeneity: Implications for planetesimal alteration conditions and sample return missions 119205 EN Christian Potiszil Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Tsutomu Ota Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Masahiro Yamanaka Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Katsura Kobayashi Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Ryoji Tanaka Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Eizo Nakamura Pheasant Memorial Laboratory, Institute for Planetary Materials, Okayama University Carbonaceous chondrites (CC) and asteroid return samples contain amino acids (AA), which are essential for an origin of life on the early Earth and can provide important information concerning planetesimal alteration processes. While many studies have investigated AA from CC, separate studies have often found differing abundances for the same meteorite. Accordingly, analytical bias, differing terrestrial contamination levels and intrinsic sample heterogeneity have been proposed as potential reasons. However, current analytical techniques allow for the analysis of several mg-sized samples and can thus enable an investigation of AA heterogeneity within single meteorite specimens. Here, such an analytical technique is applied to characterise the AA in triplicate aliquots of three CCs. The results indicate that CCs are heterogenous in terms of their AA at the mm-scale. Furthermore, the results help to further constrain the effects of planetesimal alteration on organic matter and the requirements of future sample return missions that aim to obtain organic-bearing extraterrestrial materials. No potential conflict of interest relevant to this article was reported.

American Astronomical Society Acta Medica Okayama 0004-637X 965 1 2024 Unraveling the Cr Isotopes of Ryugu: An Accurate Aqueous Alteration Age and the Least Thermally Processed Solar System Material 52 EN Ryoji Tanaka The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Dilan M. Ratnayake The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Tsutomu Ota The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Noah Miklusicak The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Tak Kunihiro The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Christian Potiszil The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Chie Sakaguchi The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Katsura Kobayashi The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Hiroshi Kitagawa The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Masahiro Yamanaka The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Masanao Abe Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Akiko Miyazaki Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Aiko Nakato Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Satoru Nakazawa Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Masahiro Nishimura Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Tatsuaki Okada Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Takanao Saiki Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Satoshi Tanaka Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Fuyuto Terui Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Yuichi Tsuda Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Tomohiro Usui Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Sei-ichiro Watanabe Department of Earth and Planetary Sciences, Nagoya University Toru Yada Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Kasumi Yogata Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Makoto Yoshikawa Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Eizo Nakamura The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University The analysis of samples returned from the C-type asteroid Ryugu has drastically advanced our knowledge of the evolution of early solar system materials. However, no consensus has been obtained on the chronological data, which is important for understanding the evolution of the asteroid Ryugu. Here, the aqueous alteration age of Ryugu particles was determined by the Mn–Cr method using bulk samples, yielding an age of 4.13 + 0.62/−0.55 Myr after the formation of Ca–Al-rich inclusions (CAI). The age corresponds to 4563.17 + 0.60/−0.67 Myr ago. The higher 55Mn/52Cr, ε54Cr, and initial ε53Cr values of the Ryugu samples relative to any carbonaceous chondrite samples implies that its progenitor body formed from the least thermally processed precursors in the outermost region of the protoplanetary disk. Despite accreting at different distances from the Sun, the hydrous asteroids (Ryugu and the parent bodies of CI, CM, CR, and ungrouped C2 meteorites) underwent aqueous alteration during a period of limited duration (3.8 ± 1.8 Myr after CAI). These ages are identical to the crystallization age of the carbonaceous achondirtes NWA 6704/6693 within the error. The ε54Cr and initial ε53Cr values of Ryugu and NWA 6704/6693 are also identical, while they show distinct Δ'17O values. This suggests that the precursors that formed the progenitor bodies of Ryugu and NWA 6703/6693 were formed in close proximity and experienced a similar degree of thermal processing in the protosolar nebula. However, the progenitor body of Ryugu was formed by a higher ice/dust ratio, than NWA6703/6693, in the outer region of the protoplanetary disk. No potential conflict of interest relevant to this article was reported.

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

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

MDPI AG Acta Medica Okayama 1999-4915 16 7 2024 Metatranscriptomic Sequencing of Sheath Blight-Associated Isolates of Rhizoctonia solani Revealed Multi-Infection by Diverse Groups of RNA Viruses 1152 EN Michael Louie R. Urzo Microbiology Division, Institute of Biological Sciences, College of Arts and Sciences, University of the Philippines Los Baños Timothy D. Guinto Microbiology Division, Institute of Biological Sciences, College of Arts and Sciences, University of the Philippines Los Baños Ana Eusebio-Cope Fit-for-Future Genetic Resources Unit, Rice Breeding Innovations Department, International Rice Research Institute (IRRI), University of the Philippines Los Baños Bernard O. Budot Institute of Weed Science, Entomology, and Plant Pathology, College of Agriculture and Food Science, University of the Philippines Los Baños Mary Jeanie T. Yanoria Traits for Challenged Environments Unit, Rice Breeding Innovations Department, International Rice Research Institute (IRRI), University of the Philippines Los Baños Gilda B. Jonson Traits for Challenged Environments Unit, Rice Breeding Innovations Department, International Rice Research Institute (IRRI), University of the Philippines Los Baños Masao Arakawa Faculty of Agriculture, Meijo University Hideki Kondo Plant-Microbe Interactions Group, Institute of Plant Science and Resources (IPSR), Okayama University Nobuhiro Suzuki Plant-Microbe Interactions Group, Institute of Plant Science and Resources (IPSR), Okayama University Rice sheath blight, caused by the soil-borne fungus Rhizoctonia solani (teleomorph: Thanatephorus cucumeris, Basidiomycota), is one of the most devastating phytopathogenic fungal diseases and causes yield loss. Here, we report on a very high prevalence (100%) of potential virus-associated double-stranded RNA (dsRNA) elements for a collection of 39 fungal strains of R. solani from the rice sheath blight samples from at least four major rice-growing areas in the Philippines and a reference isolate from the International Rice Research Institute, showing different colony phenotypes. Their dsRNA profiles suggested the presence of multiple viral infections among these Philippine R. solani populations. Using next-generation sequencing, the viral sequences of the three representative R. solani strains (Ilo-Rs-6, Tar-Rs-3, and Tar-Rs-5) from different rice-growing areas revealed the presence of at least 36 viruses or virus-like agents, with the Tar-Rs-3 strain harboring the largest number of viruses (at least 20 in total). These mycoviruses or their candidates are believed to have single-stranded RNA or dsRNA genomes and they belong to or are associated with the orders Martellivirales, Hepelivirales, Durnavirales, Cryppavirales, Ourlivirales, and Ghabrivirales based on their coding-complete RNA-dependent RNA polymerase sequences. The complete genome sequences of two novel RNA viruses belonging to the proposed family Phlegiviridae and family Mitoviridae were determined. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1424-8220 25 12 2025 Effects of Sampling Frequency on Human Activity Recognition with Machine Learning Aiming at Clinical Applications 3780 EN Takahiro Yamane Department of Biomedical Informatics, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Moeka Kimura Faculty of Health Sciences, Okayama University Medical School Mizuki Morita Department of Biomedical Informatics, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Human activity recognition using wearable accelerometer data can be a useful digital biomarker for severity assessment and the diagnosis of diseases, where the relationship between onset and patient activity is crucial. For long-term monitoring in clinical settings, the volume of data collected over time should be minimized to reduce power consumption, computational load, and communication volume. This study aimed to determine the lowest sampling frequency that maintains recognition accuracy for each activity. Thirty healthy participants wore nine-axis accelerometer sensors at five body locations and performed nine activities. Machine-learning-based activity recognition was conducted using data sampled at 100, 50, 25, 20, 10, and 1 Hz. Data from the non-dominant wrist and chest, which have previously shown high recognition accuracy, were used. Reducing the sampling frequency to 10 Hz did not significantly affect the recognition accuracy for either location. However, lowering the frequency to 1 Hz decreases the accuracy of many activities, particularly brushing teeth. Using data with a 10 Hz sampling frequency can maintain recognition accuracy while decreasing data volume, enabling long-term patient monitoring and device miniaturization for clinical applications. No potential conflict of interest relevant to this article was reported.

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

Japan Association of Mineralogical Sciences Acta Medica Okayama 1345-6296 120 1 2025 Metamorphic pressure-temperature conditions of garnet granulite from the Eastern Iratsu body in the Sambagawa belt, SW Japan 241001 EN Daisuke NAKAMURA Faculty of Environmental, Life, Natural Science and Technology, Okayama University Mutsuki AOYA Graduate School of Technology, Industrial and Social Sciences, Tokushima University Tomoki OKAMURA Graduate School of Natural Science and Technology, Okayama University Several coarse-grained mafic bodies with evidence for eclogite-facies metamorphism are present in the Besshi area of the Sambagawa subduction-type metamorphic belt, SW Japan. Among them the granulite-bearing Eastern Iratsu metagabbro body involves an unresolved problem of whether it originated in the hanging-wall or footwall side of the subduction zone. The key to settle this problem is its relationship with the adjacent Western Iratsu metabasaltic body, which includes thick marble layer and certainly has the footwall ocean-floor origin. Several previous studies consider that the Western and Eastern Iratsu bodies were originally coherent in the footwall side and formed the shallower and deeper parts of a thick oceanic crust, respectively. The validity of this hypothesis may be assessed by deriving pressure-temperature history of the Eastern Iratsu body, or especially the pressure (depth) condition of the granulite-facies metamorphism before the eclogite-facies overprinting because, if the pressure was relatively high, the oceanic crust assumed in the above hypothesis might be too thick to tectonically achieve the present-day adjacence of the two bodies on the geological map. This study petrologically analyzes a garnet-bearing granulite from the Eastern Iratsu body and newly reports stable coexistence of garnet and orthopyroxene in the sample. By utilizing a garnet-orthopyroxene geothermobarometer, the minimum P-T conditions of the granulite-facies stage was estimated to be 0.8 GPa (∼ 27 km in depth) and 780 °C. If the Western and Eastern Iratsu bodies were assumed to have formed a coherent oceanic crust before their subduction, the original thickness of it was >27 km and this demands unusually strong ductile shortening (<1/9) or unrealistically large vertical displacement on intraplate faulting, suggesting invalidity of the assumption. The Western and Eastern Iratsu bodies, therefore, are originally bounded by subduction-boundary fault and the obtained pressure of 0.8 GPa can be interpreted to represent that of the hanging-wall lower continental crust in the subduction zone, where the Eastern Iratsu body originated. After the granulite-facies metamorphism, the Western Iratsu body, which was located near the footwall surface, initiated subduction and was subsequently juxtaposed with the above-located Eastern Iratsu body at the corresponding depth (∼ 27 km or greater) along the subduction boundary. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0340-7004 74 7 2025 HIF-PH inhibitors induce pseudohypoxia in T cells and suppress the growth of microsatellite stable colorectal cancer by enhancing antitumor immune responses 192 EN Yuehua Chen 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 Yusuke Hamada Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuze Wang Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miao Tian Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Noma Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hiroshi Tazawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Recent studies have revealed that CD8+ T cells can be activated via genetic upregulation of HIF-1 alpha, thereby augmenting antitumor effector functions. HIF-1 alpha upregulation can be attained by inhibiting HIF-prolyl hydroxylase (HIF-PH) under normoxic conditions, termed pseudohypoxia. This study investigated whether pseudohypoxia induced by HIF-PH inhibitors suppresses Microsatellite stable (MSS) colorectal cancer (CRC) by affecting tumor immune response. Methods The HIF-PH inhibitors Roxadustat and Vadadustat were utilized in this study. In vitro, we assessed the effects of HIF-PH inhibitors on human and murine colon cancer cell lines (SW480, HT29, Colon26) and murine T cells. In vivo experiments were performed with mice bearing Colon26 tumors to evaluate the effect of these inhibitors on tumor immune responses. Tumor and spleen samples were analyzed using immunohistochemistry, RT-qPCR, and flow cytometry to elucidate potential mechanisms. Results HIF-PH inhibitors demonstrated antitumor effects in vivo but not in vitro. These inhibitors enhanced the tumor immune response by increasing the infiltration of CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs). HIF-PH inhibitors induced IL-2 production in splenic and intratumoral CD4+ T cells, promoting T cell proliferation, differentiation, and immune responses. Roxadustat synergistically enhanced the efficacy of anti-PD-1 antibody for MSS cancer by increasing the recruitment of TILs and augmenting effector-like CD8+ T cells. Conclusion Pseudohypoxia induced by HIF-PH inhibitors activates antitumor immune responses, at least in part, through the induction of IL-2 secretion from CD4+ T cells in the spleen and tumor microenvironment, thereby enhancing immune efficacy against MSS CRC. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1476-4598 24 1 2025 ADAR1-high tumor-associated macrophages induce drug resistance and are therapeutic targets in colorectal cancer 116 EN Hibiki Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiaki Takahashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Moriwake Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshitaka Kondo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Sho Takeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shuya Yano Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuki Matsumi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Kishimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hideki Yamamoto Department of Clinical Genomic Medicine, 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 Masashi Kayano Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Michiue Neutron Therapy Research Center, Okayama University Keiichiro Nakamura Department of Obstetrics and Gynecology, Okayama University Gradu�ate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshiko Mori 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 Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuzo Umeda 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 Ajay Goel Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute, City of Hope Comprehensive Cancer Center Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background Colorectal cancer (CRC) is considered the third most common type of cancer worldwide. Tumor-associated macrophages (TAMs) have been shown to promote drug resistance. Adenosine-to-inosine RNA-editing, as regulated by adenosine deaminase acting on RNA (ADAR), is a process that induces the posttranscriptional modification of critical oncogenes. The aim of this study is to determine whether the signals from cancer cells would induce RNA-editing in macrophages. Methods The effects of RNA-editing on phenotypes in macrophages were analyzed using clinical samples and in vitro and in vivo models. Results The intensity of the RNA-editing enzyme ADAR1 (Adenosine deaminase acting on RNA 1) in cancer and mononuclear cells indicated a strong positive correlation between the nucleus and cytoplasm. The ADAR1-positive mononuclear cells were positive for CD68 and CD163, a marker for M2 macrophages. Cancer cells transport pro-inflammatory cytokines or ADAR1 protein directly to macrophages via the exosomes, promoting RNA-editing in AZIN1 (Antizyme Inhibitor 1) and GLI1 (Glioma-Associated Oncogene Homolog 1) and resulting in M2 macrophage polarization. GLI1 RNA-editing in the macrophages induced by cancer cells promotes the secretion of SPP1, which is supplied to the cancer cells. This activates the NF kappa B pathway in cancer cells, promoting oxaliplatin resistance. When the JAK inhibitors were administered, oncogenic RNA-editing in the macrophages was suppressed. This altered the macrophage polarization from M2 to M1 and decreased oxaliplatin resistance in cancer cells. Conclusions This study revealed that ADAR1-high TAMs are crucial in regulating drug resistance in CRC and that targeting ADAR1 in TAMs could be a promising treatment approach for overcoming drug resistance in CRC. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 0737-3937 43 6 2025 Spray-drying of polymer solutions across a broad concentration range and the subsequent formation of a few micro- ∼nano-meter sized fibers 1108 1116 EN Chika Araga Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University Kaito Fukushima Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University Haruna Sato Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University Nao Honda Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University Takato Hasegawa Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University Koichi Nakaso Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University Naoyuki Ishida Department of Chemical Engineering and Material Sciences, Faculty of Science and Engineering, Doshisha University Koreyoshi Imamura Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University Spray drying is a widely utilized technique for the concentration and fine particulation of dried products. This study demonstrated that a versatile spray dryer, equipped with a two-fluid nozzle atomizer, can convert polymer solutions into nanoscale fibers by manipulating the conditions of the polymer solutions. The polymers employed in this research included polyvinylpyrrolidones (Mw 24.5 k to 60 kDa), dextrans (70 k to 450–650 kDa), pullulan, gum Arabic, Eudragit and agar, with methanol and water serving as solvents. Various combinations of polymers and solvents were subjected to spray drying at polymer concentrations ranging from 5 to 1000 g/L. Scanning electron microscopy analyses of the spray-dried samples indicated that the products transitioned from micrometer-sized particles to sub-micrometer fibers in several instances when the polymer concentrations exceeded specific threshold levels. The investigation also explored the relationship between these threshold concentrations and the surface tension and viscosity of the polymer solutions. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 2 2025 Relationship between Personality Traits and Postpartum Depressive Symptoms in Women who Became Pregnant via Infertility Treatment 109 116 EN Kyoko Awai Graduate School of Health Sciences, Okayama University Mikiya Nakatsuka Faculty of Health Sciences, Okayama University Original Article 10.18926/AMO/68649 The status of postpartum depression was elucidated herein with the use of the Edinburgh Postnatal Depression Scale (EPDS) in women in Shikoku, Japan who became pregnant and gave birth after undergoing infertility treatment, including assisted reproductive technology (ART). The assessment was performed during their children’s 4-month health examination. The relationships between postpartum depression and the mothers’ background factors and scores on the Big Five personality traits scale were also examined. Of the Big Five personality traits, the scores for neuroticism were significantly higher in the ART group (n=71) than in the general infertility treatment (n=118) and natural pregnancy (n=872) groups. No significant differences in EPDS scores were seen among these three groups. A logistic regression analysis showed that neuroticism was associated with an EPDS score ≧9 points, (which is suggestive of postpartum depression, ) in all groups. Moreover, although a long-standing marriage had an inhibitory effect on postpartum depression in the natural pregnancy group, no such trend was seen in the ART group, which included many women with long-standing marriages. Particularly for women who become pregnant by ART, an individualized response that pays close attention to the woman’s personality traits is needed. 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.

MDPI Acta Medica Okayama 2227-9032 13 6 2025 Effects of Trehalose on Halitosis: A Randomized Cross-Over Clinical Trial 619 EN Hisataka Miyai Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takaaki Tomofuji Department of Community Oral Health, School of Dentistry, Asahi University Hirofumi Mizuno Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Manabu Morita Department of Oral Health Sciences, Faculty of Health Care Sciences, Takarazuka University of Medical and Health Care Momoko Nakahara Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital Kota Kataoka Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital Ichiro Sumita Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital Yurika Uchida Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital Naoki Toyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aya Yokoi Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Reiko Yamanaka-Kohno Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital Noriko Takeuchi Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital Takayuki Maruyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Halitosis is a condition characterized by an unpleasant malodor. Intra-oral halitosis is caused by volatile sulfur compounds (VSCs) and can be associated with oral dryness. Trehalose is one of the materials used to relieve oral dryness. The aim of the present study was to investigate the effect of trehalose on halitosis. Methods: This prospective, double-blinded, placebo-controlled, cross-over study enrolled volunteers from Okayama University Hospital. The participants were randomly divided into two groups, with one group receiving trehalose (a 10% trehalose solution) and the other receiving a placebo (distilled water) in a 1:1 allocation. The primary study outcome was the subjective organoleptic test. The secondary outcomes were the concentrations of the VSCs, which were measured using a portable gas chromatography device, and the oral moisture status, which was measured using an oral moisture meter. The planned sample size was 10 participants based on the previous study. Results: The final intention-to-treat analysis was performed using the data from 9 participants. After applying 10% trehalose as an oral spray, the organoleptic score decreased in a time-dependent manner. However, no significant differences were seen between the trehalose and placebo groups. In terms of secondary outcomes, the oral moisture levels increased immediately after the trehalose spray application, and significant differences in the amount of change from the baseline were seen between the trehalose and placebo groups (p = 0.047). No significant differences were seen in any of the other variables (p > 0.05). Conclusions: We could not identify any positive effects on halitosis from a one-time 10% trehalose application as an oral spray in this prospective, double-blinded, placebo-controlled, cross-over study. However, the trehalose application immediately improved the oral moisture levels and was useful for treating oral dryness. No potential conflict of interest relevant to this article was reported.

岡山大学教育学部 Acta Medica Okayama 0471-4008 87 1991 日常生活における援助希求行動 ―キャンベラの事例― 63 83 EN MASAO NOBE 10.18926/bgeou/68588 　This paper reports a study that investigated perceived sources of daily support. To gather empirical evidence, a sample survey of women in four study areas of Canberra was conducted in 1986-1987. Three hundred and ninety-four women who were under 55 years of age and who were married or in a de facto relationship were interviewed. They responded to six hypothetical difficult situations by identifying the first source from which they would seek support. Analysis of the data has revealed the following ; 　(1) When respondents had their relatives in Canberra, they regarded their relatives as the chief source of daily support. However, there were many residents without local relatives in Canberra. For such respondents, their relatives were not so helpful in daily support. Incidentally, workmates were thought of as much less important providers of support than relatives, neighbours or friends. 　(2) Social networks were differentiated in that respondents tended to depend on types of people appropriate to individual difficult situations. 　(3) Dependable friends and workmates tended to live closer than dependable relatives. 　(4) Dependable relatives were usually limited to immediate family, such as parents (-in-law), brothers (-in-law) or sisters (-in-law). No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 15 1 2025 Local-structure insight into the improved superconducting properties of Pb-substituted La(O, F)BiS2: a photoelectron holography study 8366 EN Yajun Li Graduate School of Natural Science and Technology, Okayama University Yusuke Hashimoto Nara Institute of Science and Technology (NAIST) Noriyuki Kataoka Graduate School of Natural Science and Technology, Okayama University Zexu Sun Nara Institute of Science and Technology (NAIST) Sota Kawamura Nara Institute of Science and Technology (NAIST) Hiroto Tomita Nara Institute of Science and Technology (NAIST) Taro Setoguchi Graduate School of Natural Science and Technology, Okayama University Soichiro Takeuchi Nara Institute of Science and Technology (NAIST) Shunjo Koga Nara Institute of Science and Technology (NAIST) Kohei Yamagami Japan Synchrotron Radiation Research Institute (JASRI) Yoshinori Kotani Japan Synchrotron Radiation Research Institute (JASRI) Satoshi Demura Department of Physics, College of Science and Technology(CST), Nihon University Kanako Noguchi Tokyo University of Science Hideaki Sakata Tokyo University of Science Tomohiro Matsushita Nara Institute of Science and Technology (NAIST) Takanori Wakita Graduate School of Natural Science and Technology, Okayama University Yuji Muraoka Graduate School of Natural Science and Technology, Okayama University Takayoshi Yokoya Graduate School of Natural Science and Technology, Okayama University Pb-substituted La(O, F)BiS2 (Pb-LaOFBiS2) exhibits improved superconducting properties and a resistivity anomaly around 100 K that is attributed to a structural transition. We have performed temperature(T)-dependent photoelectron holography (PEH) to study dopant incorporation sites and the local structure change across the anomaly. The PEH study of Pb-LaOFBiS2 provided evidence for the dominant incorporation sites of Pb and F: Pb atoms are incorporated into the Bi sites and F atoms are incorporated into the O site. No remarkable difference in the local structures around Pb and Bi atoms was observed. Across the temperature of the resistivity anomaly (T*), photoelectron holograms of Bi 4f changed. Comparisons of holograms with those of non-substituted LaOFBiS2 sample, as well as simulated holograms, suggested that (1), above T*, the tetragonal structure of Pb-LaOFBiS2 is different from the tetragonal structure of LaOFBiS2 and (2), below T*, the tetragonal structure still remains in Pb-LaOFBiS2. We discuss a possible origin of the difference in the structure above T* and the implication of the result below T*, which are necessary ingredients to understand the physical properties of Pb-LaOFBiS2. No potential conflict of interest relevant to this article was reported.

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

Japan Society of Hydrology and Water Resources Acta Medica Okayama 1882-3416 19 1 2025 Evaluation of the temporal behavior of fulvic acid iron in Asahi River, Okayama, Japan 36 43 EN Rohdof Lactem Yengeh Graduate School of Environmental and Life Science, Okayama University Hiroaki Somura Graduate School of Environmental and Life Science, Okayama University Toshitsugu Moroizumi Graduate School of Environmental and Life Science, Okayama University Yasushi Mori Graduate School of Environmental and Life Science, Okayama University Morihiro Maeda Graduate School of Environmental and Life Science, Okayama University Iron is essential for biogeochemical processes in aquatic ecosystems, but its riverine concentration can be affected by environmental conditions. This study assessed weekly fulvic acid iron (FAFe) concentration at a single sampling site in Asahi River from 2022–2023 to explore the differences in the temporal scales. The objectives of this study were to evaluate the effects of physicochemical properties of the river on the concentration of FAFe, analyze the concentration of FAFe in spring, summer, autumn and winter, and assess the relationship between FAFe concentration and land use types of the watershed. The results indicated that physicochemical parameters, such as pH and surface water temperature (SWT) seemed to influence FAFe concentration (p < 0.05). Hydrological dynamics influenced FAFe concentration and transport, revealing an increasing trend during spring (p < 0.001) and summer (p = 0.05), with non-significant trends during autumn and winter (p > 0.05). FAFe exhibited a strong positive correlation with total organic carbon (TOC) (p < 0.001). Upland fields significantly influenced FAFe concentration (p < 0.01) through runoff with abundant NO3– and PO43– into the river. Thus, FAFe concentration in Asahi River was influenced by pH, SWT, TOC, hydrological regime, and agricultural runoff. No potential conflict of interest relevant to this article was reported.

Springer Nature Acta Medica Okayama 2731-4383 5 1 2025 Voice analysis and deep learning for detecting mental disorders in pregnant women: a cross-sectional study 12 EN Hikaru Ooba Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jota Maki Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction Perinatal mental disorders are prevalent, affecting 10-20% of pregnant women, and can negatively impact both maternal and neonatal outcomes. Traditional screening tools, such as the Edinburgh Postnatal Depression Scale (EPDS), present limitations due to subjectivity and time constraints in clinical settings. Recent advances in voice analysis and machine learning have shown potential for providing more objective screening methods. This study aimed to develop a deep learning model that analyzes the voices of pregnant women to screen for mental disorders, thereby offering an alternative to the traditional tools. Methods A cross-sectional study was conducted among 204 pregnant women, from whom voice samples were collected during their one-month postpartum checkup. The audio data were preprocessed into 5000 ms intervals, converted into mel-spectrograms, and augmented using TrivialAugment and context-rich minority oversampling. The EfficientFormer V2-L model, pretrained on ImageNet, was employed with transfer learning for classification. The hyperparameters were optimized using Optuna, and an ensemble learning approach was used for the final predictions. The model's performance was compared to that of the EPDS in terms of sensitivity, specificity, and other diagnostic metrics. Results Of the 172 participants analyzed (149 without mental disorders and 23 with mental disorders), the voice-based model demonstrated a sensitivity of 1.00 and a recall of 0.82, outperforming the EPDS in these areas. However, the EPDS exhibited higher specificity (0.97) and precision (0.84). No significant difference was observed in the area under the receiver operating characteristic curve between the two methods (p = 0.759). Discussion The voice-based model showed higher sensitivity and recall, suggesting that it may be more effective in identifying at-risk individuals than the EPDS. Machine learning and voice analysis are promising objective screening methods for mental disorders during pregnancy, potentially improving early detection. Conclusion We developed a lightweight machine learning model to analyze pregnant women's voices for screening various mental disorders, achieving high sensitivity and demonstrating the potential of voice analysis as an effective and objective tool in perinatal mental health care. No potential conflict of interest relevant to this article was reported.

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

Nature Portfolio Acta Medica Okayama 2045-2322 15 1 2025 Novel treatment strategy targeting interleukin-6 induced by cancer associated fibroblasts for peritoneal metastasis of gastric cancer 3267 EN Ema Mitsui 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 Tomohiro Okura Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Une Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriyuki Nishiwaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Ohara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junko Ohtsuka Laboratory of Fundamental Oncology, National Cancer Center Research Institute Rieko Ohki Laboratory of Fundamental Oncology, National Cancer Center Research Institute Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Cancer-associated fibroblasts (CAFs) are a crucial component in the tumor microenvironment (TME) of peritoneal metastasis (PM), where they contribute to tumor progression and metastasis via secretion of interleukin-6 (IL-6). Here, we investigated the role of IL-6 in PM of gastric cancer (GC) and assessed whether anti-IL-6 receptor antibody (anti-IL-6R Ab) could inhibit PM of GC. We conducted immunohistochemical analysis of IL-6 and alpha-smooth muscle (alpha-SMA) expressions in clinical samples of GC and PM, and investigated the interactions between CAFs and GC cells in vitro. Anti-tumor effects of anti-IL-6R Ab on PM of GC were investigated in an orthotopic murine PM model. IL-6 expression was significantly correlated with alpha-SMA expression in clinical samples of GC, and higher IL-6 expression in the primary tumor was associated with poor prognosis of GC. Higher IL-6 and alpha-SMA expressions were also observed in PM of GC. In vitro, differentiation of fibroblasts into CAFs and chemoresistance were observed in GC cells cocultured with fibroblasts. Anti-IL-6R Ab inhibited the progression of PM in GC cells cocultured with fibroblasts in the orthotopic mouse model but could not inhibit the progression of PM consisting of GC cells alone. IL-6 expression in the TME was associated with poor prognosis of GC, and CAFs were associated with establishment and progression of PM via IL-6. Anti-IL-6R Ab could inhibit PM of GC by the blockade of IL-6 secreted by CAFs, which suggests its therapeutic potential for PM of GC. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2079-6374 15 1 2025 Mapping Surface Potential in DNA Aptamer-Neurochemical and Membrane-Ion Interactions on the SOS Substrate Using Terahertz Microscopy 46 EN Kosei Morita Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yuta Mitsuda Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Sota Yoshida Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toshihiko Kiwa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jin Wang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University In this study, we utilized a terahertz chemical microscope (TCM) to map surface potential changes induced by molecular interactions on silicon-on-sapphire (SOS) substrates. By functionalizing the SOS substrate with DNA aptamers and an ion-selective membrane, we successfully detected and visualized aptamer-neurochemical complexes through the terahertz amplitude. Additionally, comparative studies of DNA aptamers in PBS buffer and artificial cerebrospinal fluid (aCSF) were performed by computational structure modeling and terahertz measurements. Beyond neurochemicals, we also investigated calcium ions, measuring their concentrations in PDMS-fabricated micro-wells using minimal sample volumes. Our results highlight the capability of TCM as a powerful, label-free, and sensitive platform for the probing and mapping of surface potential arising from molecular interactions, with broad implications for biomedical diagnostics and research. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-431X 14 1 2025 An Investigation of Hand Gestures for Controlling Video Games in a Rehabilitation Exergame System 25 EN Radhiatul Husna Department of Information and Communication Systems, Okayama University Komang Candra Brata Department of Information and Communication Systems, Okayama University Irin Tri Anggraini Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Alfiandi Aulia Rahmadani Department of Electrical Engineering, State Polytechnic of Malang Chih-Peng Fan Department of Electrical Engineering, National Chung Hsing University Musculoskeletal disorders (MSDs) can significantly impact individuals' quality of life (QoL), often requiring effective rehabilitation strategies to promote recovery. However, traditional rehabilitation methods can be expensive and may lack engagement, leading to poor adherence to therapy exercise routines. An exergame system can be a solution to this problem. In this paper, we investigate appropriate hand gestures for controlling video games in a rehabilitation exergame system. The Mediapipe Python library is adopted for the real-time recognition of gestures. We choose 10 easy gestures among 32 possible simple gestures. Then, we specify and compare the best and the second-best groups used to control the game. Comprehensive experiments are conducted with 16 students at Andalas University, Indonesia, to find appropriate gestures and evaluate user experiences of the system using the System Usability Scale (SUS) and User Experience Questionnaire (UEQ). The results show that the hand gestures in the best group are more accessible than in the second-best group. The results suggest appropriate hand gestures for game controls and confirm the proposal's validity. In future work, we plan to enhance the exergame system by integrating a diverse set of video games, while expanding its application to a broader and more diverse sample. We will also study other practical applications of the hand gesture control function. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1936-0851 18 52 2024 Bright Quantum-Grade Fluorescent Nanodiamonds 35202 35213 EN Keisuke Oshimi Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University Hitoshi Ishiwata The National Institutes for Quantum Science and Technology (QST), Institute for Quantum Life Science (iQLS) Hiromu Nakashima Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University Sara Mandić Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University Hina Kobayashi Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University Minori Teramoto Advanced Materials Laboratory, Sumitomo Electric Industries, Ltd. Hirokazu Tsuji Advanced Materials Laboratory, Sumitomo Electric Industries, Ltd. Yoshiki Nishibayashi Advanced Materials Laboratory, Sumitomo Electric Industries, Ltd. Yutaka Shikano Institute of Systems and Information Engineering, University of Tsukuba Toshu An School of Materials Science, Japan Advanced Institute of Science and Technology Masazumi Fujiwara Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University Optically accessible spin-active nanomaterials are promising as quantum nanosensors for probing biological samples. However, achieving bioimaging-level brightness and high-quality spin properties for these materials is challenging and hinders their application in quantum biosensing. Here, we demonstrate bright fluorescent nanodiamonds (NDs) containing 0.6–1.3-ppm negatively charged nitrogen-vacancy (NV) centers by spin-environment engineering via enriching spin-less 12C-carbon isotopes and reducing substitutional nitrogen spin impurities. The NDs, readily introduced into cultured cells, exhibited improved optically detected magnetic resonance (ODMR) spectra; peak splitting (E) was reduced by 2–3 MHz, and microwave excitation power required was 20 times lower to achieve a 3% ODMR contrast, comparable to that of conventional type-Ib NDs. They show average spin-relaxation times of T1 = 0.68 ms and T2 = 3.2 μs (1.6 ms and 5.4 μs maximum) that were 5- and 11-fold longer than those of type-Ib, respectively. Additionally, the extended T2 relaxation times of these NDs enable shot-noise-limited temperature measurements with a sensitivity of approximately 0.28K/√Hz. The combination of bulk-like NV spin properties and enhanced fluorescence significantly improves the sensitivity of ND-based quantum sensors for biological applications. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 2635-0998 2 3 2023 All-in-one terahertz taste sensor: integrated electronic and bioelectronic tongues 620 626 EN Jin Wang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kenji Sakai Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toshihiko Kiwa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Taste sensors, also known as electronic tongues or bioelectronic tongues, are designed to evaluate food and beverages, as well as for medical diagnostics. These devices mimic the ability of the human tongue to detect and identify different tastes in liquid samples, such as sweet, sour, salty, bitter, and umami. In this study, a novel all-in-one terahertz taste sensor was proposed, which differs from traditional electrochemical approaches. This sensor utilizes terahertz technology for imaging and sensing chemical reactions on the terahertz semiconductor emitter surface. The surface can be functionalized with ion-sensitive membranes, proteins, DNA aptamers, and organic receptors, enabling the detection of various substances, such as solution pH, physiological ions, sugars, toxic chemicals, drugs, and explosives. Terahertz taste sensors offer several advantages, including being label-free, high sensitivity and selectivity, rapid response, minimal sample consumption, and the ability to detect non-charged chemical substances. By integrating multiple receptors or sensing materials on a single chip, the all-in-one terahertz taste sensor has significant potential for future taste substance detection, nutrition evaluation, metabolite and drug monitoring, and biomarker sensing. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 63 21 2024 Endoscopic and Histological Gastritis in University Students with Helicobacter pylori Infection 2875 2884 EN Shotaro Okanoue Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Sakae Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Yokota Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuka Obayashi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Makoto Abe Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiyasu Kono Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromitsu Kanzaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Yanai Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objective Although the characteristics of Helicobacter pylori infection have been extensively reported, there is a lack of consensus regarding its characteristics in young adults. The present study examined the endoscopic and histological characteristics of young adults who underwent eradication therapy for H. pylori infection. Methods We examined the H. pylori infection status of first-year students at Okayama University School of Medicine and Dentistry between 2014 and 2020. A total of 152 (6.8%) students who were positive for H. pylori antibody or pepsinogen tests were enrolled in the study. Among them, 107 students underwent endoscopy, and their biopsy samples were investigated. Seventy-five students were diagnosed with H. pylori infections. Results Of 75 H. pylori-positive patients, 57 (76.0%) had endoscopic atrophic gastritis, and 42 (56.0%) had histological atrophy. A few patients had severe atrophic gastritis. All 65 patients who underwent an eradication assessment were successfully treated. After successful eradication, 26 patients underwent endoscopic follow-up. The mean follow-up period was 32.9 months. A histological evaluation revealed that gastric antrum atrophy had subsided in 11 of 14 patients, and atrophy in the lesser curvature of the gastric body had subsided in 7 of 8 patients. Conclusion More than half of young adults with H. pylori infection had atrophic gastritis. We found mild atrophy in young adults, which subsided shortly after eradication treatment. This study provides a foundation for future studies to evaluate the validity of eradication therapy in preventing gastric cancer in patients. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0016-7037 391 2025 Magnesium isotope composition of volcanic rocks from cold and warm subduction zones: Implications for the recycling of subducted serpentinites and carbonates 158 176 EN Wei Zhang The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Hiroshi Kitagawa The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Fang Huang CAS Key Laboratory of Crust-Mantle Materials and Environments, School of Earth and Space Sciences, University of Science and Technology of China Magnesium (Mg) isotopes are regarded as a sensitive tracer to the contribution from subducted serpentinites and carbonates. However, the source, distribution, and controlling factors of the Mg isotope composition of arc magmas remain unclear. In this study, we investigated the intra-arc and inter-arc variations in Mg isotope compositions of volcanic rocks from two typical cold subduction zones [NE Japan (NEJ) and Izu arcs] and a typical hot subduction zone [SW Japan (SWJ) arc] to address the question. The volcanic rocks from the frontal-arc regions of NEJ and Izu have isotopically heavy Mg (δ26Mg = –0.20 to –0.08 ‰) compared to the mantle-like δ26Mg values of most of volcanic rocks from SWJ and the rear regions of NEJ and Izu arcs (–0.28 to –0.17 ‰). It is also worth noting that NEJ arc includes samples with δ26Mg values (–0.61 to –0.39 ‰) significantly lower than the mantle, but similar to the < 110 Ma intra-continental basalts from eastern China, which is the first observation in modern arc rocks. No obvious effects of post-eruptive alteration, fractional crystallization, partial melting, or the addition of silicate-rich sediment and oceanic crust components could be identified in the Mg isotope compositions of these volcanic rocks. By contrast, the correlations between the δ26Mg values and the proxy for serpentinite component (i.e., 11B/10B and Nb/B ratios) indicate that the component exerts a strong control on the Mg-isotopic signature of these arc rocks. Considering metamorphic reactions in subduction lithologies under P-T conditions postulated for these arcs, the variations in δ26Mg values of these arc magmas are unlikely to have been controlled by dehydration of serpentinites in subducted oceanic lithosphere (slab serpentinite). Instead, the high-δ26Mg values of frontal-arc rocks are delivered by the fluids from serpentinite formed in the lowermost part of the sub-arc mantle (mantle wedge serpentinite) in channelized flow. Comparatively, such a high-δ26Mg signature is invisible in volcanic rocks from rear-arc regions of NEJ and Izu, and the entire SWJ, suggesting that the major Mg carriers in subducted serpentinites (e.g., talc, chlorite, and serpentine) were broken down completely before subducted slabs reached the depth beneath these volcanoes. Moreover, the volcanic rocks with low δ26Mg values from the rear arc of NEJ are characterized by high La/Yb and U/Nb ratios as well as low Ti/Eu, Ti/Ti*, and Hf/Hf* ratios, suggesting the involvements of carbonates in their magma sources. The quantitative modeling suggests that < 20 % of sedimentary carbonate (dolomite) was recycled into their mantle source, revealing that Mg-rich carbonate could be incorporated into a deep mantle wedge at rear-arc depths of 150–400 km in subduction zones. No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 4 2025 吉備製鉄遺跡周辺地域の磁鉄鉱ざくろ石スカルン鉄鉱石の鉱物学的・地球化学的特徴 19 52 EN Yasushi TAKECHI Kurashiki Museum of Natural History Daisuke NAKAMURA Okayama University, Department of Earth Sciences Shigeyuki SUZUKI Okayama University, Department of Earth Sciences Joseph RYAN Okayama University, Research Institute for the Dynamics of Civilizations Takeshi UWAGAKI Okayama Prefectural Board of Education Masato NAGAHARA The Historical Study Group of Mining and Metallurgy of Japan Yuta YOSHIE Mitsui Mining & Smelting Co., Ltd. Kei IKEHATA University of Tsukuba, Faculty of Life and Environmental Sciences Osamu KIMURA Okayama University, Research Institute for the Dynamics of Civilizations Ryoichi HATTORI Osaka University, Graduate School of Humanities 論文 (Research article) 10.18926/67954 We conducted mineralogical and geochemical analysis of ore samples taken from locations surrounding the Jinmu, Sanpō, and Kōmoto mines in order to determine the source of iron ore uncovered from archaeological sites. The mineral composition of the magnetite-garnet bearing skarn deposits varies from mine to mine: while clinopyroxene and amphibole are present in the Jinmu and Sanpō samples, only a small amount of clinopyroxene occurs in the Kōmoto samples. The chemical compositions of magnetite and garnet are distinctive for each mine. Among the trace elements contained in the magnetite, Mg and Mn tend to be higher in the Kōmoto samples, Ti in the Jinmu samples, and Ca and Si in the Sanpō samples. The garnet from all the mines is andradite, but while the Kōmoto samples contain almost no Al, it is present in the Jinmu and Sanpō samples. Although samples were taken from a limited number of mine areas (three), our analysis provides an index for comparison with iron ore uncovered from archaeological sites, which will aid in provenance determination. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0009-2673 97 11 2024 Refined surface area determination of graphene oxide using methylene blue as a probe molecule: a comparative approach uoae118 EN Israel Ortiz-Anaya Graduate School of Natural Sciences and Technology, Okayama University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University In this research, we explored the effectiveness of the methylene blue adsorption method as an alternative approach for determining the specific surface area of graphene oxide. Initially, through a comparative analysis with reference activated carbon, we identified the limitations of utilizing N2 physisorption for specific surface area determination of graphene oxide. Our findings revealed that the standard pretreatment process (heating under vacuum) before N2 physisorption led to damage to the surface oxygen groups on graphene oxide, and the measured surface areas (43 m2/g) do not accurately represent the entire surface area. To optimize methylene blue coverage on graphene oxide, we conducted adsorption equilibrium experiments, focusing on controlling temperature and pH. The pH was significantly important in regulating the coverage of methylene blue. Under the optimized methylene blue adsorption conditions, the specific surface area of graphene oxide was 1,555 m2/g. Our assumptions regarding specific surface area calculations were supported by structural characterization of samples with varying methylene blue uptakes. The results confirmed a uniform coverage of methylene blue on graphene oxide by scanning electron microscopy and energy dispersive X-ray, X-ray diffraction, and atomic force microscopy. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 14 1 2024 ADAR1 could be a potential diagnostic target for intrauterine infection patients 29419 EN Keiichiro Nakamura Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Thuy Ha Vu Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Jota Maki Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kazuhiro Okamoto Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hisashi Masuyama Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Intrauterine infection (IUI) is mainly an ascending infection in which vaginal and cervical pathogens ascend to the uterus and can affect the fetus. Until now, there is still no effective diagnostic biomarker for IUI, such as chorioamnionitis (CAM) and funisitis (FUN). Deoxyribonucleic acid (DNA)/Ribonucleic acid (RNA) editing molecules such as apolipoprotein-B mRNA-editing complex (APOBEC) 3 families and Adenosine deaminase family acting on RNA (ADAR)1 were examined in chorioamniotic membranes and umbilical cord of 83 patient samples. Furthermore, Ureaplasma parvum induced ADAR1 was investigated in human HTR-8/SVneo EVT cell line. ADAR1 had a significantly higher area under the curve (AUC) (0.721 and 0.745) than other APOBEC3s or cytokines in CAM and FUN patients. In vitro, ureaplasma parvum was demonstrated to activate ADAR1 (p = 0.025) and reduce RIG-I, IRF3, IFN-α, and IFN-β expression in EVT cell line (p = 0.005, p = 0.010, p < 0.001, and p = 0.018, respectively). High expression of ADAR1 was strongly associated with CAM and FUN patients (multivariate analyses; p = 0.035 and p = 0.002). ADAR1 could be a potential diagnostic target for IUI, such as CAM and FUN patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 6 2024 Traumatic Neuroma Arising from Surgical Trauma during Conversion from Laparoscopic to Open Cholecystectomy 459 464 EN Shinya Sakamoto Department of Gastroenterological Surgery, Kochi Health Sciences Center Motoyasu Tabuchi Department of Gastroenterological Surgery, Kochi Health Sciences Center Rika Yoshimatsu Department of Radiology, Kochi Health Sciences Center Manabu Matsumoto Department of Diagnostic Pathology, Kochi Health Sciences Center Jun Iwata Department of Diagnostic Pathology, Kochi Health Sciences Center Takehiro Okabayashi Department of Gastroenterological Surgery, Kochi Health Sciences Center Case Report 10.18926/AMO/67872 Traumatic neuroma is an abnormal proliferation of injured nerves resulting from trauma or surgery. We present a case of traumatic neuroma arising in the cystic duct after cholecystectomy. A 66-year-old man was referred to our department due to a biliary tumor. He had undergone cholecystectomy 20 years prior. Cholangioscopy showed an elevated lesion covered with smooth mucosa. Histological examination revealed normal bile duct mucosa. Although benign disease was suspected, the possibilities of malignant disease could not be excluded. Extrahepatic bile duct resection was planned to include intraoperative rapid-freezing of a biopsy specimen followed by histopathological examination. These intraoperative histology results showed proliferation of nerve and fibrous tissue only, resulting in the diagnosis of traumatic neuroma, so no lymph nodes were removed. To avoid excessive surgical intervention, histopathological examination of an intraoperative rapid-frozen biopsy specimen may be important for diagnosing traumatic neuroma. No potential conflict of interest relevant to this article was reported.

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

Nature Portfolio Acta Medica Okayama 2045-2322 14 1 2024 Apolipoprotein-B mRNA-editing complex 3B could be a new potential therapeutic target in endometriosis 24968 EN Thuy Ha Vu Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Keiichiro Nakamura Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Chiaki Kashino Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kazuhiro Okamoto Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kotaro Kubo Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuhiko Kamada Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hisashi Masuyama Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine This study investigated the correlation of Apolipoprotein-B mRNA-editing complex 3B (APOBEC3B) expression with hypoxia inducible factor 1α (HIF-1α), Kirsten rat sarcoma virus (KRAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in endometriosis patients, and the inhibitory effects of APOBEC3B knockdown in a human endometriotic cell line. Here, APOBEC3B, HIF-1α, KRAS, and PIK3CA were examined in patients with and without endometriosis using reverse transcription polymerase chain reaction (RT-PCR). The apoptosis, cell proliferation, invasion, migration, and biological function of APOBEC3B knockdown were explored in 12Z immortalized human endometriotic cell line. We observed APOBEC3B, HIF-1α, KRAS and PIK3CA expressions were significantly higher in endometriosis patients (p < 0.001, p < 0.001, p = 0.029, p = 0.001). Knockdown of APOBEC3B increased apoptosis, which was 28.03% and 22.27% higher than in mock and control siRNA samples, respectively. APOBEC3B knockdown also decreased PIK3CA expression and increased Caspase 8 expression, suggesting a potential role in the regulation of apoptosis. Furthermore, knockdown of APOBEC3B significantly inhibited cell proliferation, invasion, and migration compared to mock and control siRNA. (Cell proliferation: mock: p < 0.001 and control siRNA: p = 0.049. Cell invasion: mock: p < 0.001 and control siRNA: p = 0.029. Cell migration: mock: p = 0.004, and control siRNA: p = 0.014). In conclusion, this study suggests that APOBEC3B may be a new potential therapeutic target for endometriosis. No potential conflict of interest relevant to this article was reported.

Institute of Electrical and Electronics Engineers Acta Medica Okayama 2169-3536 12 2024 MUSIC Spectrum Based Interference Detection, Localization, and Interference Arrival Prediction for mmWave IRS-MIMO System 142592 142605 EN Yafei Hou Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kazuto Yano Wave Engineering Laboratories, Advanced Telecommunications Research Institute International Norisato Suga Wave Engineering Laboratories, Advanced Telecommunications Research Institute International Julian Webber Wave Engineering Laboratories, Advanced Telecommunications Research Institute International Satoshi Denno Faculty of Environmental, Life, Natural Science and Technology, Okayama University Toshikazu Sakano Wave Engineering Laboratories, Advanced Telecommunications Research Institute International For a millimeter wave (mmWave) intelligent re-configurable surface (IRS)-MIMO system, if it can correctly detect the interference occurrence and their locations, the patterns of interference signal can be collected and learned using machine learning for the prediction of interference arrival. With the information of interference location and activity pattern, the capacity of the system can be largely improved using many techniques such as beamforming, interference cancellation, and transmission scheduling. This paper aims to detect interference occurrence using a low-complexity MUSIC (MUSIC: multiple signal classification) spectrum-based method, and then localize their sources for mmWave IRS-MIMO system. The MUSIC spectrum of wireless system can be regarded as somehow the 'signature' related to the signals transmitted from different users or interference. We utilize such property to detect the occurrence of interference, and then localize their sources in a low-complexity way. Finally, the pattern of interference occurrence can be learned to predict the interference arrival from the collected data. This paper also proposed an efficient probabilistic neural network (PNN)-based predictor for the interference arrival prediction and showed its prediction accuracy. From simulated results, our proposed method can achieve the correct results with the accuracy near to 100% when the fingerprint samples is over 10. In addition, the localization error can be within 1 m with more than 65% and 43% for Y-axis and X-axis, respectively. Finally, based on the results of the interference occurrence, the proposed PNN-based predictor for the interference arrival prediction can capture correctly the similar distribution function of the coming continuous idle status. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 Occult Nesidioblastosis Detected by 111In-Pentetreotide Single-Photon Emission Computed Tomography 423 428 EN Shinya Sakamoto Department of Gastroenteorlogical Surgery, Kochi Health Sciences Center Motoyasu Tabuchi Department of Gastroenteorlogical Surgery, Kochi Health Sciences Center Rika Yoshimatsu Department of Radiology, Kochi Health Sciences Center Ai Hishida Department of Endocrinology and Metabolism, 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 Gastroenteorlogical Surgery, Kochi Health Sciences Center Case Report 10.18926/AMO/67667 Nesidioblastosis, also known as persistent hyperinsulinemic hypoglycemia, is usually observed in children and infants, although more recently adult-onset nesidioblastosis has also been described. We present a case of nesidioblastosis in a 78-year-old man that was detected by 111In-pentetreotide single photon emission computed tomography (SPECT/CT). The patient was transferred to our hospital’s emergency department in a hypoglycemic coma. Dynamic enhanced CT could detect no lesion in the pancreas, but an 111In-pentetreotide SPECT/CT scan performed after a similar episode four weeks later showed increased focal uptake at the head of the pancreas. The results of a selective arterial calcium injection test were negative. After careful consideration and discussion among colleagues, surgical intervention was selected, and a pancreaticoduodenectomy was performed. On histology, there were elevated numbers of Langerhans islets in the pancreatic head, and the islets themselves appeared enlarged. Hypertrophic β-cells comprised the majority, but α-cells, δ-cells and pancreatic polypeptide were also detected in the islets. Based on the histopathological results and repeated hyperinsulinemic hypoglycemic crises, the patient was finally diagnosed with adult-onset nesidioblastosis. He had no hypoglycemic symptoms during outpatient follow-up examination. Since 111In-pentetreotide SPECT/CT may be able to detect nesidioblastosis, clinicians should consider this relatively new-modality examination when encountering such cases. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 Effect of Radon Inhalation on Murine Brain Proteins: Investigation Using Proteomic and Multivariate Analyses 387 399 EN Shota Naoe Graduate School of Health Sciences, Okayama University Ayumi Tanaka Graduate School of Health Sciences, Okayama University Norie Kanzaki Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Reiju Takenaka Graduate School of Health Sciences, Okayama University Akihiro Sakoda Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Takaaki Miyaji Advanced Science Research Center, Okayama University Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Takahiro Kataoka Faculty of Health Sciences, Okayama University Original Article 10.18926/AMO/67663 Radon is a known risk factor for lung cancer; however, it can be used beneficially, such as in radon therapy. We have previously reported the enhancement of antioxidant effects associated with trace amounts of oxidative stress as one of the positive biological effects of radon inhalation. However, the biological effects of radon inhalation are incompletely understood, and more detailed and comprehensive studies are required. Although several studies have used proteomics to investigate the effects of radon inhalation on body proteins, none has focused on brain proteins. In this study, we evaluated the expression status of proteins in murine brains using proteomic and multivariate analyses to identify those whose expressions changed following two days of radon inhalation at a concentration of 1,500 Bq/m3. We found associations of radon inhalation with the expressions of seven proteins related to neurotransmission and heat shock. These proteins may be proposed as biomarkers indicative of radon inhalation. Although further studies are required to obtain the detailed biological significance of these protein alterations, this study contributes to the elucidation of the biological effects of radon inhalation as a low-dose radiation. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-2607 12 9 2024 A Novel C-Terminal Truncated Bacteriocin Found by Comparison between Leuconostoc mesenteroides 406 and 213M0 Isolated from Mongolian Traditional Fermented Milk, Airag 1781 EN Chihiro Hasiqimuge Graduate School of Environmental and Life Science, Okayama University Chihiro Hano Graduate School of Environmental and Life Science, Okayama University Kensuke Arakawa Graduate School of Environmental and Life Science, Okayama University Saki Yoshida Graduate School of Environmental and Life Science, Okayama University Junliang Zhao Graduate School of Environmental and Life Science, Okayama University Hidehiro Toh Advanced Genomics Center, National Institute of Genetics Hidetoshi Morita Graduate School of Environmental and Life Science, Okayama University Taku Miyamoto Graduate School of Environmental and Life Science, Okayama University Bacteriocins produced by lactic acid bacteria are known to be useful tools for food biopreservation and fermentation control. Leuconostoc mesenteroides subsp. mesenteroides 406 and 213M0 isolated from different samples of Mongolian traditional fermented milk, airag, had been reported to produce listericidal bacteriocin-like inhibitory substances with similar but slightly different properties. In this study, the antibacterial properties and the related gene sequences of both strains were compared, and then their bacteriocins were purified and identified. Strain 406 was superior to strain 213M0 in cell growth and antibacterial activity against many strains. However, the activity of 213M0 was stronger than that of 406 against a few strains. DNA sequencing revealed two and three plasmids in 406 and 213M0, respectively, and each one of them harbored an almost identical mesentericin Y105-B105 gene cluster. Removal of these plasmids resulted in a complete loss of activity, indicating that the antibacterial activity of both strains was generated by bacteriocins encoded on the plasmids. Mesentericins Y105 and B105 were purified from both cultures, and another novel bacteriocin, named mesentericin M, was identified from the 213M0 culture only. Its structural gene was coded on a 213M0 plasmid and, surprisingly, its C-terminal three amino acid residues were post-translationally cleaved. To our knowledge, this is the first report of a C-terminal truncated bacteriocin. In conclusion, the novel bacteriocin should be mainly responsible for the difference in antibacterial properties between the two strains. No potential conflict of interest relevant to this article was reported.

The Japan Institute of Metals and Materials Acta Medica Okayama 0021-4876 88 10 2024 Ti-10V-2Fe-3Al合金の逆形状記憶効果と靭性回復 239 244 EN Yoshito Takemoto Faculty of Environmental, Life, Natural Science and Technology, Okayama University Daiki Shinomiya Graduate School of Natural Science and Technology, Okayama University Taiki Ishihara Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroto Yokota Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Jinta Arakawa Faculty of Environmental, Life, Natural Science and Technology, Okayama University Ti-10V-2Fe-3Al alloys exhibit shape memory (SM) and reverse shape memory (RSM) effects. When an alloy sample that has been strained by external force at room temperature is heated, the strain recovers and SM effect develops at around 300℃, but as the temperature increases further, the shape changes in the opposite direction due to RSM effect at around 450℃. This RSM effect has potential applications in forming processes such as thin-walled pipes, but has the disadvantage that the RSM treatment makes the material very brittle. Therefore, in this study, a heat treatment to restore toughness while maintaining the shape after forming was investigated. The alloy quenched from 1050℃ had a microstructure consisting of a β matrix phase and α′′-martensite (α′′Mq). Differential scanning calorimetry (DSC) results showed that the continuous heating process occurred in the following order: α′′Mq → β reverse transformation, ω formation, ω disappearance, thermally induced α′′iso phase formation, α precipitation and α → β transformation. Ageing at 300℃, where the SM effect appears, caused significant embrittlement due to the formation of the ageing ω phase. Ageing treatment at 450℃, where the RSM effect is obtained, resulted in the formation of a fine α phase, which also caused significant embrittlement. On the other hand, additional aging at 600℃ for 1.8 ks after RSM treatment significantly improved the toughness and produced material properties comparable to aerospace material specifications. It was found that the embrittlement in the RSM treatment was due to the precipitation of fine α phase, and that the growth of α phase with a width of about 0.2 µm or more was required for toughness recovery. It was also found that the specimen shape formed by the RSM treatment hardly changed after the additional heat treatment of 1.8 ks at 600℃. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1472-6831 24 1 2024 Histological differences related to autophagy in the minor salivary gland between primary and secondary types of Sjögren's syndrome 1099 EN Hitomi Ono-Minagi Department of Cytology and Histology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tsutomu Nohno Department of Cytology and Histology, Okayama University Medical School Kiyofumi Takabatake Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takehiro Tanaka Department of Pathology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayuki Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Hospital Kohta Miyawaki Division of Precision Medicine, Kyushu University School of Medicine Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, 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 Seiji Iida Department of Oral and Maxillofacial Reconstructive Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yoshino Department of Pathology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayoshi Sakai Department of Rehabilitation for Orofacial Disorders, Osaka University Graduate School of Dentistry Hideyo Ohuchi Department of Cytology and Histology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Some forms of Sjögren’s syndrome (SS) follow a clinical course accompanied by systemic symptoms caused by lymphocyte infiltration and proliferation in the liver, kidneys, and other organs. To better understand the clinical outcomes of SS, here we used minor salivary gland tissues from patients and examine their molecular, biological, and pathological characteristics. A retrospective study was performed, combining clinical data and formalin-fixed paraffin-embedded (FFPE) samples from female patients over 60 years of age who underwent biopsies at Okayama University Hospital. We employed direct digital RNA counting with nCounter® and multiplex immunofluorescence analysis with a PhenoCycler™ on the labial gland biopsies. We compared FFPE samples from SS patients who presented with other connective tissue diseases (secondary SS) with those from stable SS patients with symptoms restricted to the exocrine glands (primary SS). Secondary SS tissues showed enhanced epithelial damage and lymphocytic infiltration accompanied by elevated expression of autophagy marker genes in the immune cells of the labial glands. The close intercellular distance between helper T cells and B cells positive for autophagy-associated molecules suggests accelerated autophagy in these lymphocytes and potential B cell activation by helper T cells. These findings indicate that examination of FFPE samples from labial gland biopsies can be an effective tool for evaluating molecular histological differences between secondary and primary SS through multiplexed analysis of gene expression and tissue imaging. No potential conflict of interest relevant to this article was reported.

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

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

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

Elsevier BV Acta Medica Okayama 1387-1811 378 2024 Mesoporous carbon with extremely low micropore content synthesized from graphene oxide modified with alkali metal nitrates 113269 EN Zhao Li Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Moeto Toyota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takahiro Ohkubo Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University High-temperature thermal exfoliation is a simple, rapid, and cost-efficient method for transforming graphene oxide (GO) materials into reduced graphene oxide (rGO) materials. In this study, GO materials were dispersed with alkali metal nitrates (MNO3), leading to the preparation of porous rGO materials characterized by high specific surface area (SSA) and pore volume via high-temperature thermal exfoliation. Experimental data indicate that the metal cations of MNO3 tend to react directly with the oxygen functional groups (OFG) of GO, modulating the OFG content. Simultaneously, nitrate anions have preferential interaction with alkali metal ions and adhere to the surface of the GO. The presence of MNO3 on the surface of GO facilitates the thermal exfoliation process and leads to the formation of structures with an extremely high proportion of mesoporous content. The isothermal gas adsorption results show that the exfoliation efficiency of the samples activated with different nitrate salts decreases in the order rGO-KNO3 > rGO-NaNO3 > rGO-LiNO3. Among these samples, rGO modified with KNO3 exhibited the greatest exfoliation efficiency, with a mesopore-to-micropore volume ratio of 22.4, more than 1.7 times that of rGO. Its SSA and pore volume were 359 m2 g−1 and 1.26 cm3 g−1, respectively. These values significantly surpass those of rGO. Our research findings demonstrate that activation with MNO3 significantly increases the SSA and pore volume of the GO material after high-temperature annealing. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 15 2024 Increased Oxidative Stress and Decreased Citrulline in Blood Associated with Severe Novel Coronavirus Pneumonia in Adult Patients 8370 EN Mitsuru Tsuge Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Kou Hasegawa Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenichiro Kudo Department of Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Yasushi Tanimoto Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Kazuhiro Nouso Department of Gastroenterology, Okayama City Hospital Naohiro Oda Department of Internal Medicine, Fukuyama City Hospital Sho Mitsumune Department of Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Goro Kimura Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Haruto Yamada Department of Infectious Disease, Okayama City Hospital Ichiro Takata Department of Internal Medicine, Fukuyama City Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Akihiko Taniguchi Department of Allergy and Respiratory Medicine, Okayama University Hospital Kohei Tsukahara Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyuki Aokage Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hideharu Hagiya Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrine Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Tsukahara Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University This study investigated the correlation between oxidative stress and blood amino acids associated with nitric oxide metabolism in adult patients with coronavirus disease (COVID-19) pneumonia. Clinical data and serum samples were prospectively collected from 100 adult patients hospitalized for COVID-19 between July 2020 and August 2021. Patients with COVID-19 were categorized into three groups for analysis based on lung infiltrates, oxygen inhalation upon admission, and the initiation of oxygen therapy after admission. Blood data, oxidative stress-related biomarkers, and serum amino acid levels upon admission were compared in these groups. Patients with lung infiltrations requiring oxygen therapy upon admission or starting oxygen post-admission exhibited higher serum levels of hydroperoxides and lower levels of citrulline compared to the control group. No remarkable differences were observed in nitrite/nitrate, asymmetric dimethylarginine, and arginine levels. Serum citrulline levels correlated significantly with serum lactate dehydrogenase and C-reactive protein levels. A significant negative correlation was found between serum levels of citrulline and hydroperoxides. Levels of hydroperoxides decreased, and citrulline levels increased during the recovery period compared to admission. Patients with COVID-19 with extensive pneumonia or poor oxygenation showed increased oxidative stress and reduced citrulline levels in the blood compared to those with fewer pulmonary complications. These findings suggest that combined oxidative stress and abnormal citrulline metabolism may play a role in the pathogenesis of COVID-19 pneumonia. No potential conflict of interest relevant to this article was reported.

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 45 11 2022 Investigation of the Expression of Serine Protease in Vibrio vulnificus 1596 1601 EN Tomoka Kawase Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Anusuya Debnath Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tamaki Mizuno Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yui Miyake Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Vibrio vulnificus is a Gram-negative estuarine bacterium that causes infection in immuno-compromised patients, eels, and shrimp. V. vulnificus NCIMB2137, a metalloprotease-negative strain isolated from a diseased eel, produces a 45-kDa chymotrypsin-like alkaline serine protease known as VvsA. The gene encoding vvsA also includes another gene, vvsB with an unknown function; however, it is assumed to be an essential molecular chaperone for the maturation of VvsA. In the present study, we used an in vitro cell-free translation system to examine the maturation pathway of VvsA. We individually expressed the vvsA and vvsB genes and detected their mRNAs. However, the sample produced from vvsA did not exhibit protease activity. A sodium dodecyl sulfate (SDS) analysis detected the VvsB protein, but not the VvsA protein. A Western blotting analysis using a histidine (His)-tag at the amino terminus of proteins also showed no protein production by vvsA. These results suggested the translation, but not the transcription of vvsA. Factors derived from Escherichia coli were used in the in vitro cell-free translation system employed in the present study. The operon of the serine protease gene containing vvsA and vvsB was expressed in E. coli. Although serine proteases were produced, they were cleaved at different sites and no active mature forms were detected. These results indicate that the operon encoding vvsA and vvsB is a gene constructed to be specifically expressed in V. vulnificus. No potential conflict of interest relevant to this article was reported.

IOS Press Acta Medica Okayama 1387-2877 100 1 2024 A Novel Peptidome Technology for the Diagnosis of Mild Cognitive Impairment and Alzheimer’s Disease by Selected Reaction Monitoring 219 228 EN Yusuke Fukui Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koh Tadokoro Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Minaki Hamada Protosera, Inc. Kyoichi Asada Protosera, Inc. Lyang-Ja Lee Protosera, Inc. Hidehisa Tachiki Protosera, Inc. Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, National Center of Neurology and Psychiatry Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background:With the aging of populations worldwide, Alzheimer’s disease (AD) has become a concern due to its high prevalence and the continued lack of established treatments. Early diagnosis is required as a preventive intervention to modify the disease’s progression. In our previous study, we performed peptidomic analysis of serum samples obtained from AD patients and age-matched healthy subjects to seek peptide biomarker candidates for AD by using BLOTCHIP-MS analysis, and identified four peptides as AD biomarker candidates. Objective:The objective was to validate the serum biomarker peptides to distinguish mild cognitive impairment (MCI) and AD in comparison to cognitively healthy controls using a new peptidome technology, the Dementia Risk Test. Methods:We enrolled 195 subjects with normal cognitive function (NC; n = 70), MCI (n = 55), and AD (n = 70), The concentrations of cognitive impairment marker peptides (Fibrinogen α chain (FAC), Fibrinogen β chain (FBC), Plasma protease C1 inhibitor (PPC1I), α2-HS-glycoprotein (AHSG)) were quantified by using a selected reaction monitoring assay based on liquid chromatography-MS/MS. Results:The present study confirmed that three peptides, FAC, FBC, and PPC1I, were significantly upregulated during the onset of AD. This three-peptide set was both highly sensitive in determining AD (sensitivity: 85.7%, specificity: 95.7%, AUC: 0.900) and useful in distinguishing MCI (sensitivity: 61.8%, specificity: 98.6%, AUC: 0.824) from NC. Conclusions:In this validation study, we confirmed the high diagnostic potential of the three peptides identified in our previous study as candidate serum biomarkers for AD. The Dementia Risk Test may be a powerful tool for detecting AD-related pathological changes. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0167-6806 208 2024 Comparison of proportions and prognostic impact of pathological complete response between evaluations of representative specimen and total specimen in primary breast cancer after neoadjuvant chemoradiotherapy: an ancillary study of JCOG0306 145- 154 EN Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Hitoshi Tsuda Department of Basic Pathology, National Defense Medical College Keita Sasaki JCOG Data Center/Operations Office, National Cancer Center Hospital Junki Mizusawa JCOG Data Center/Operations Office, National Cancer Center Hospital Futoshi Akiyama Department of Pathology, Cancer Institute Hospital Masafumi Kurosumi Department of Diagnostic Pathology, Kameda Kyobashi Clinic Masataka Sawaki Department of Breast Oncology, Aichi Cancer Center Hospital Nobuko Tamura Department of Breast Surgery, Toranomon Hospital Kiyo Tanaka Department of Breast Surgery, Toranomon Hospital Takahiro Kogawa Department of Breast Medical Oncology, Cancer Institute Hospital Mina Takahashi Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center Naoki Hayashi Department of Breast Surgery Oncology, St Lukes International Hospital Hirofumi Mukai Department of Breast and Medical Oncology, National Cancer Center Hospital East Norikazu Masuda Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital Fumikata Hara Department of Breast Medical Oncology, Cancer Institute Hospital Hiroji Iwata Department of Breast Oncology, Aichi Cancer Center Hospital Background In JCOG0306 trial, a phase II study to examine the efficacy of neoadjuvant chemotherapy followed by radiation therapy (NAC-RT) to primary breast cancer, pathological complete response (pCR) was evaluated from specimens of the representative cross-section including the tumor center that had been accurately marked [representative specimen (RS) method]. In this ancillary study, we examined if the RS method was comparable to the conventional total specimen (TS) method, which is widely employed in Japan, to identify the pCR group showing excellent prognosis. Methods We obtained long-term follow-up data of 103 patients enrolled in JCOG0306 trial. As histological therapeutic effect, pCR (ypT0 and ypT0/is) and quasi-pCR [QpCR, ypT0/is plus Grade 2b (only a few remaining invasive cancer cells)] were evaluated with RS and TS methods. Concordance of pCR between these two methods and associations of the pCR with prognosis were examined. Results ypT0, ypT0/is, and QpCR were observed in 28 (27.2%), 39 (37.9%), and 45 (43.7%) patients with RS method, whereas these were 20 (19.4%), 25 (24.3%) and 40 (38.9%) with TS method, respectively. Between RS and TS methods, concordance proportions of ypT0 and ypTis were 92.2% and 86.4%, respectively. Risk of recurrence of ypT0/is group was lower than that of non-ypT0/is group (HR 0.408, 95% CI [0.175–0.946], P = 0.037) and risk of death of ypT0/is group was lower than that of non-ypT0/is group (HR 0.251, 95% CI [0.073–0.857], P = 0.027). The ypT0 and ypT0/is groups with RS method showed excellent prognosis similarly with those with TS method, and RS method was able to differentiate the OS and RFS between pCR and non-pCR than TS method significantly even if pCR was classified ypT0 or ypT0/is. With TS method, QpCR criteria stratified patients into the better and worse prognosis groupsmore clearly than pCR criteria of ypT0 or ypT0/is. Conclusions RS method was comparable to TS method for the evaluation of pCR in the patients who received NAC-RT to primary breast cancer provided the tumor center was accurately marked. As pCR criteria with RS method, ypT0/is appeared more appropriate than ypT0. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 3 2024 The Role of the Lipid Profile and Oxidative Stress in Fatigue, Sleep Disorders and Cognitive Impairment in Patients with Multiple Sclerosis 259 270 EN Gonul Vural Department of Neurology, Faculty of Medicine, Ankara Yildirim Beyazit University Esra Demir Department of Neurology, Ankara City Hospital Sadiye Gumusyayla Department of Neurology, Faculty of Medicine, Ankara Yildirim Beyazit University Funda Eren Department of Clinical Biochemistry, Ankara City Hospital Serdar Barakli Department of Neurology, Ankara City Hospital Salim Neselioglu Department of Clinical Biochemistry, Ankara City Hospital Ozcan Erel Department of Clinical Biochemistry, Ankara City Hospital Original Article 10.18926/AMO/67201 The aim of this study is to investigate the relationship of the lipid profile, dysfunctional high-density lipoprotein, ischaemia-modified albumin and thiol–disulfide homeostasis with cognitive impairment, fatigue and sleep disorders in patients with multiple sclerosis. The cognitive functions of patients were evaluated with the Brief International Cognitive Assessment for Multiple Sclerosis battery. Fatigue was evaluated with the Fatigue Severity Scale and the Fatigue Impact Scale. The Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale were used to assess patients’ sleep disturbance. Peripheral blood samples were collected, and lipid levels and myeloperoxidase and paraoxonase activity were measured. The myeloperoxidase/paraoxonase ratio, which indicates dysfunctional high-density lipoprotein, was calculated. Thiol–disulfide homeostasis and ischaemia-modified albumin were measured. We did not identify any relationship between dysfunctional high-density lipoprotein and the physical disability, cognitive decline, fatigue and sleep problems of multiple sclerosis. Thiol–disulfide homeostasis was associated with cognitive scores. The shift of the balance towards disulfide was accompanied by a decrease in cognitive scores. On the other hand, we did not detect any relationship between fatigue and sleep disorders and thiol–disulfide homeostasis. Our findings revealed a possible correlation between cognitive dysfunction and thiol–disulfide homeostasis in multiple sclerosis 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.

Elsevier Acta Medica Okayama 2352-1864 35 2024 Effects of cellulose nanofibers on soil water retention and aggregate stability 103650 EN An Thuy Ngo Graduate School of Environmental and Life Science, Okayama University Yasushi Mori Graduate School of Environmental and Life Science, Okayama University Long Thanh Bui Graduate School of Environmental and Life Science, Okayama University Innovative solutions that address global challenges such as water scarcity and soil erosion are critical for maintaining sustainable agriculture. Due to their water-absorbing and soil-binding properties, cellulose nanofibers (CNF) can be applied to soil to enhance soil water retention and aggregate stability. In this study, we analyzed the effects of the drying temperature, dosage, irrigation water quality, and soil type on the efficacy of CNFs. Our results revealed that CNF dried at 5 degrees C is more effective at absorbing water than others, and adding 1% CNF enhanced soil water content up to 98%. The CNF samples absorbed water due to their hydrophilic molecular groups and morphological structure, as confirmed by Fourier-transform infrared spectroscopy and scanning electron microscopy. CNF addition increased the soil volumetric water content and prolonged water retention by 22 days in the paddy soil samples, highlighting its potential for drought-prone areas. Furthermore, irrigation water quality, such as pH and cation values, influenced the interactions between CNF and water molecules, suggesting adjustments to the water retention curve. In its hydrated state, CNF promotes colloid flocculation and binds to soil particles, thereby strengthening the bonds crucial for aggregate formation and stability. CNF enhanced macro-aggregate formation by up to 48% and 59% in the masa and paddy soil samples, respectively. Our study emphasizes the potential of CNF for water conservation, soil health, and overall agricultural sustainability. 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.

American Society for Clinical Investigation Acta Medica Okayama 2379-3708 9 10 2024 Double-faced CX3CL1 enhances lymphangiogenesis-dependent metastasis in an aggressive subclone of oral squamous cell carcinoma e174618 EN Htoo Shwe Eain 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 Masaaki Nakayama Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University May Wathone Oo Department of Oral Pathology and 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 Universit Yoko Fukuhara Department of Oral Morphology, 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 Quisheng Shan 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 Kisho Ono Department of Oral and Maxillofacial Surgery, 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 Nobuyoshi Mizukawa Department of Oral and Maxillofacial Reconstructive Surgery, 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 Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Because cancer cells have a genetically unstable nature, they give rise to genetically different variant subclones inside a single tumor. Understanding cancer heterogeneity and subclone characteristics is crucial for developing more efficacious therapies. Oral squamous cell carcinoma (OSCC) is characterized by high heterogeneity and plasticity. On the other hand, CX3C motif ligand 1 (CX3CL1) is a double-faced chemokine with anti- and pro -tumor functions. Our study reported that CX3CL1 functioned differently in tumors with different cancer phenotypes, both in vivo and in vitro. Mouse OSCC 1 (MOC1) and MOC2 cells responded similarly to CX3CL1 in vitro. However, in vivo, CX3CL1 increased keratinization in indolent MOC1 cancer, while CX3CL1 promoted cervical lymphatic metastasis in aggressive MOC2 cancer. These outcomes were due to double-faced CX3CL1 effects on different immune microenvironments indolent and aggressive cancer created. Furthermore, we established that CX3CL1 promoted cancer metastasis via the lymphatic pathway by stimulating lymphangiogenesis and transendothelial migration of lymph -circulating tumor cells. CX3CL1 enrichment in lymphatic metastasis tissues was observed in aggressive murine and human cell lines. OSCC patient samples with CX3CL1 enrichment exhibited a strong correlation with lower overall survival rates and higher recurrence and distant metastasis rates. In conclusion, CX3CL1 is a pivotal factor that stimulates the metastasis of aggressive cancer subclones within the heterogeneous tumors to metastasize, and our study demonstrates the prognostic value of CX3CL1 enrichment in long-term monitoring in OSCC. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-163X 14 4 2024 Swelling Stress of Bentonite: Thermodynamics of Interlayer Water in K-Montmorillonite in Consideration of Alteration 430 EN Misato Endo Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haruo Sato Institute of Academic and Research, Okayama University The buffer material that makes up the geological disposal system of high-level waste swells by contact with groundwater and seals space with rock mass and fractures in rock mass. The buffer material has a function of mechanical buffer with rock pressure, and swelling stress is important in this case. The alteration of bentonite may occur due to the initial replacement of cations (Na+ ions) in the interlayer with K+ ions upon contact with groundwater, but there are no studies on the swelling stress of K-bentonite. In this study, the author prepared K-montmorillonite samples and obtained thermodynamic data on interlayer water as a function of water content using a relative humidity method. The swelling stress was analyzed based on a thermodynamic model developed in earlier studies and compared with measured data. The activity and the relative partial molar Gibbs free energy of porewater decreased with decreasing water content in the region, below approximately 15%. This behavior significantly differs from that of other ions, such as Na. The swelling stress calculated based on the thermodynamic model and date occurred in the region of high density of 1.9 Mg/m3 with montmorillonite partial density. It was indicated for the first time that K-bentonite scarcely swells under realistic design conditions. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0032-3896 55 12 2023 Effect of the blend ratio of cyclic and linear polyethylene blends on isothermal crystallization in the quiescent state 1393 1398 EN Keiko Kobayashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hironori Atarashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Shinichi Yamazaki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kunio Kimura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The role of entanglements that form between cyclic and linear polymers in crystallization is of particular interest, but it is not fully understood. We investigated the crystallization behaviors of blends of cyclic polyethylene (C-PE) and linear polyethylene (L-PE) in a quiescent state to elucidate the role of this novel entanglement in crystallization. The samples were prepared by mixing the prepared C-PE and L-PE specimens at L-PE weight fraction (ΦL-PE) values of 0–100 wt%, with the weight average molecular weights of C-PE and L-PE being 175 × 103 and 154 × 103, respectively. The isothermal crystallization behaviors were analyzed through polarizing optical microscopy (POM) and differential scanning calorimetry (DSC). The morphology observed through POM was similar to that of ΦL-PE. From the time evolution of the heat flow measured via DSC, we obtained the half-crystallization time (t1/2) values as functions of ΦL-PE at different degrees of supercooling (ΔT). The 1/t1/2 values of the C-PE and L-PE homopolymers were approximately the same at ΔT = 25.5 and 26.5 K. At a larger ΔT value, the 1/t1/2 value of C-PE was significantly larger than that of L-PE. In contrast, 1/t1/2 reached a minimum value at ΦL-PE = 30–40 wt%, irrespective of ΔT. As the entanglement density increased with increasing ΦL-PE, the crystallization rate was expected to decrease monotonically. By considering the experimental relationship between 1/t1/2 and ΦL-PE, we speculated that the suppression of crystallization in the blended system was caused by a novel entanglement formed by the penetration of the L-PE chain into the C-PE chain. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0387-7604 46 4 2024 Exploration of urine metabolic biomarkers for new-onset, untreated pediatric epilepsy: A gas and liquid chromatography mass spectrometry-based metabolomics study 180 186 EN Tomoyuki Akiyama Department of Pediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Saigusa Laboratory of Biomedical and Analytical Sciences, Faculty of Pharma-Science, Teikyo University Takushi Inoue Department of Pediatric Neurology, NHO Okayama Medical Center Chiho Tokorodani Department of Pediatrics, Kochi Health Sciences Center Mari Akiyama Department of Pediatrics (Child Neurology), Okayama University Hospital Rie Michiue Department of Pediatrics (Child Neurology), Okayama University Hospital Atsushi Mori Department of Neurology, Shiga Medical Center for Children Eiji Hishinuma Tohoku Medical Megabank Organization, Tohoku University Naomi Matsukawa Tohoku Medical Megabank Organization, Tohoku University Takashi Shibata Department of Pediatrics (Child Neurology), Okayama University Hospital Hiroki Tsuchiya Department of Pediatrics (Child Neurology), Okayama University Hospital Katsuhiro Kobayashi Department of Pediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objective: The discovery of objective indicators for recent epileptic seizures will help confirm the diagnosis of epilepsy and evaluate therapeutic effects. Past studies had shortcomings such as the inclusion of patients under treatment and those with various etiologies that could confound the analysis results significantly. We aimed to minimize such confounding effects and to explore the small molecule biomarkers associated with the recent occurrence of epileptic seizures using urine metabolomics. Methods: This is a multicenter prospective study. Subjects included pediatric patients aged 2 to 12 years old with new-onset, untreated epilepsy, who had had the last seizure within 1 month before urine collection. Controls included healthy children aged 2 to 12 years old. Those with underlying or chronic diseases, acute illnesses, or recent administration of medications or supplements were excluded. Targeted metabolome analysis of spot urine samples was conducted using gas chromatography (GC)- and liquid chromatography (LC)-tandem mass spectrometry (MS/MS). Results: We enrolled 17 patients and 21 controls. Among 172 metabolites measured by GC/MS/MS and 41 metabolites measured by LC/MS/MS, only taurine was consistently reduced in the epilepsy group. This finding was subsequently confirmed by the absolute quantification of amino acids. No other metabolites were consistently altered between the two groups. Conclusions: Urine metabolome analysis, which covers a larger number of metabolites than conventional biochemistry analyses, found no consistently altered small molecule metabolites except for reduced taurine in epilepsy patients compared to healthy controls. Further studies with larger samples, subjects with different ages, expanded target metabolites, and the investigation of plasma samples are required. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1471-230X 24 1 2024 Endoscopic manifestation of intestinal transplant-associated microangiopathy after stem cell transplantation 140 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daisuke Ennishi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nobuharu Fujii Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ken-Ichi Matsuoka Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshihiro Inokuchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background Endoscopic features of intestinal transplant-associated microangiopathy (iTAM) have not been comprehensively investigated. This study aimed to examine the endoscopic characteristics of patients diagnosed with iTAM. Methods This retrospective analysis included 14 patients pathologically diagnosed with iTAM after stem cell transplantation for hematolymphoid neoplasms (n = 13) or thalassemia (n = 1). The sex, age at diagnosis, endoscopic features, and prognosis of each patient were assessed. Serological markers for diagnosing transplant-associated thrombotic microangiopathy were also evaluated. Results The mean age at the time of iTAM diagnosis was 40.2 years. Patients diagnosed based on the pathognomonic pathological changes of iTAM presented with diverse symptoms at the times of endoscopic examinations, including diarrhea (n = 10), abdominal pain (n = 5), nausea (n = 4), appetite loss (n = 2), bloody stools (n = 2), abdominal discomfort (n = 1), and vomiting (n = 1). At the final follow-up, six patients survived, while eight patients succumbed, with a median time of 100.5 days (range: 52-247) post-diagnosis. Endoscopic manifestations included erythematous mucosa (n = 14), erosions (n = 13), ulcers (n = 9), mucosal edema (n = 9), granular mucosa (n = 9), and villous atrophy (n = 4). Erosions and/or ulcers were primarily observed in the colon (10/14, 71%), followed by the ileum (9/13, 69%), stomach (4/10, 40%), cecum (5/14, 36%), duodenum (3/10, 30%), rectum (4/14, 29%), and esophagus (1/10, 10%). Cytomegalovirus infection (n = 4) and graft-versus-host disease (n = 2) coexisted within the gastrointestinal tract. Patients had de novo prolonged or progressive thrombocytopenia (6/14, 43%), decreased hemoglobin concentration (4/14, 29%), reduced serum haptoglobin level (3/14, 21%), and a sudden and persistent increase in lactate dehydrogenase level (2/14, 14%). Peripheral blood samples from 12 patients were evaluated for schistocytes, with none exceeding 4%. Conclusions This study provides a comprehensive exploration of the endoscopic characteristics of iTAM. Notably, all patients exhibited erythematous mucosa throughout the gastrointestinal tract, accompanied by prevalent manifestations, such as erosions (93%), ulcers (64%), mucosal edema (64%), granular mucosa (64%), and villous atrophy (29%). Because of the low positivity for serological markers of transplant-associated thrombotic microangiopathy in patients with iTAM, endoscopic evaluation and biopsy of these lesions are crucial, even in the absence of these serological features. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0930-2794 37 9 2023 Diagnostic accuracy of frozen section biopsy for early gastric cancer extent during endoscopic submucosal dissection: a prospective study 6736 6748 EN Mayu Kobashi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shigenao Ishikawa Department of Gastroenterology, Kagawa Prefectural Central Hospital Tomoki Inaba Department of Gastroenterology, Kagawa Prefectural Central Hospital Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuki Aoyama Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomo Kagawa Department of Gastroenterology, Kagawa Prefectural Central Hospital Yasuto Takeuchi Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital Midori Ando Department of Pathology, Kagawa Prefectural Central Hospital Satoko Nakamura Department of Pathology, Kagawa Prefectural Central Hospital Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background Accurate diagnosis of the lateral extent of early gastric cancer during endoscopic submucosal dissection (ESD) is crucial to achieve negative resection margins. Similar to intraoperative consultation with a frozen section in surgery, rapid frozen section diagnosis with endoscopic forceps biopsy may be useful in assessing tumor margins during ESD. This study aimed to evaluate the diagnostic accuracy of frozen section biopsy. Methods We prospectively enrolled 32 patients undergoing ESD for early gastric cancer. Biopsy samples for the frozen sections were randomly collected from fresh resected ESD specimens before formalin fixation. Two different pathologists independently diagnosed 130 frozen sections as “neoplasia,” “negative for neoplasia,” or “indefinite for neoplasia,” and the frozen section diagnosis was compared with the final pathological results of the ESD specimens. Results Among the 130 frozen sections, 35 were from cancerous areas, and 95 were from non-cancerous areas. The diagnostic accuracies of the frozen section biopsies by the two pathologists were 98.5 and 94.6%, respectively. Cohen’s kappa coefficient of diagnoses by the two pathologists was 0.851 (95% confidence interval: 0.837–0.864). Incorrect diagnoses resulted from freezing artifacts, a small volume of tissue, inflammation, the presence of well-differentiated adenocarcinoma with mild nuclear atypia, and/or tissue damage during ESD. Conclusions Pathological diagnosis of frozen section biopsy is reliable and can be applied as a rapid frozen section diagnosis for evaluating the lateral margins of early gastric cancer during ESD. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 2576-098X 12 12 2023 Complete genomic sequence of Vibrio fluvialis strain IDH5335 isolated from a patient with diarrhea in Kolkata, India EN Goutam Chowdhury Collaborative Research Center of Okayama University for Infectious Diseases in India at ICMR-NICED Kei Kitahara Collaborative Research Center of Okayama University for Infectious Diseases in India at ICMR-NICED Makoto Taniguchi Oral Microbiome Center, Taniguchi Dental Clinic Kazuma Uesaka Graduate School of Bioagricultural Sciences, Nagoya University Basilua Andre Muzembo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Debmalya Mitra Collaborative Research Center of Okayama University for Infectious Diseases in India at ICMR-NICED Ayumu Ohno Collaborative Research Center of Okayama University for Infectious Diseases in India at ICMR-NICED Thandavarayan Ramamurthy ICMR-National Institute of Cholera and Enteric Diseases Shanta Dutta ICMR-National Institute of Cholera and Enteric Diseases Shin-ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Asish Kumar Mukhopadhyay ICMR-National Institute of Cholera and Enteric Diseases We isolated a Vibrio fluvialis strain (IDH5335) from a stool sample collected from a patient with diarrhea. In this announcement, we report the complete genomic sequence of this organism, which was obtained by combining Illumina and Oxford Nanopore sequencing data. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0302-8933 205 10 2023 Flavobacterium okayamense sp. nov. isolated from surface seawater 346 EN Kei Kitahara Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Basilua Andre Muzembo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sho Morohoshi TechnoSuruga Laboratory Co., Ltd Tadao Kunihiro TechnoSuruga Laboratory Co., Ltd Nozomi Tazato TechnoSuruga Laboratory Co., Ltd Ayumu Ohno Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuma Uesaka Graduate School of Bioagricultural Sciences, Nagoya University Makoto Taniguchi Oral Microbiome Center, Taniguchi Dental Clinic Shin-ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Strain KK2020170T, a Gram-stain negative, yellow colony-forming bacterium, was isolated from surface seawater sampled in Kojima Bay, Okayama, Japan. Phylogenetic analysis based on the 16S rRNA gene revealed that strain KK2020170T belongs to the genus Flavobacterium, with Flavobacterium haoranii LQY-7T (98.1% similarity) being its closest relative, followed by Flavobacterium sediminis MEBiC07310T (96.9%) and Flavobacterium urocaniciphilum YIT 12746T (96.0%). Whole-genome shotgun sequencing showed that strain KK2020170T, when paralleled with F. haoranii LQY-7 T, had 81.3% average nucleotide identity, and 24.6% in silico DNA–DNA hybridization values, respectively. The DNA G + C content of strain KK2020170T was 31.1 mol%. The most abundant fatty acids (> 10%) of strain KK2020170T were iso-C15: 0, iso-C17: 0 3-OH and iso-C15: 1 G. The dominant respiratory quinone of the strain was menaquinone MK-6. Based on the phylogenetic and phenotypic analysis results, we propose that strain KK2020170T represents a novel species, for which the name Flavobacterium okayamense sp. nov. has been proposed. The type strain is KK2020170T (= ATCC TSD-280 T = NBRC 115344 T). No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0007-0920 130 9 2024 PRRX1-TOP2A interaction is a malignancy-promoting factor in human malignant peripheral nerve sheath tumours 1493 1504 EN Shota Takihira Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Yamada Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsunori Osone Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoka Takao Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Michiyuki Hakozaki Department of Orthopedic Surgery, Fukushima Medical University School of Medicine Takuto Itano Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eiji Nakata Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Kunisada Department of Orthopedic Surgery, 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 Takeshi Takarada Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Paired related-homeobox 1 (PRRX1) is a transcription factor in the regulation of developmental morphogenetic processes. There is growing evidence that PRRX1 is highly expressed in certain cancers and is critically involved in human survival prognosis. However, the molecular mechanism of PRRX1 in cancer malignancy remains to be elucidated. Methods: PRRX1 expression in human Malignant peripheral nerve sheath tumours (MPNSTs) samples was detected immunohistochemically to evaluate survival prognosis. MPNST models with PRRX1 gene knockdown or overexpression were constructed in vitro and the phenotype of MPNST cells was evaluated. Bioinformatics analysis combined with co-immunoprecipitation, mass spectrometry, RNA-seq and structural prediction were used to identify proteins interacting with PRRX1. Results: High expression of PRRX1 was associated with a poor prognosis for MPNST. PRRX1 knockdown suppressed the tumorigenic potential. PRRX1 overexpressed in MPNSTs directly interacts with topoisomerase 2 A (TOP2A) to cooperatively promote epithelial-mesenchymal transition and increase expression of tumour malignancy-related gene sets including mTORC1, KRAS and SRC signalling pathways. Etoposide, a TOP2A inhibitor used in the treatment of MPNST, may exhibit one of its anticancer effects by inhibiting the PRRX1–TOP2A interaction. Conclusion: Targeting the PRRX1–TOP2A interaction in malignant tumours with high PRRX1 expression might provide a novel tumour-selective therapeutic strategy. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2475-0328 8 3 2024 A multi-center, prospective, clinical study to evaluate the anti-reflux efficacy of laparoscopic double-flap technique (lD-FLAP Study) 374 382 EN Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Michihiro Ishida Department of Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima Yasuhiro Choda Department of Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima Atsushi Muraoka Department of Surgery, Kagawa Rosai Hospital Shinji Hato Department of Surgery, Shikoku Cancer Center Tetsuya Kagawa Department of Surgery, Shikoku Cancer Center Norimitsu Tanaka Department of Surgery, Kagawa Prefectural Central Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiko Nishizaki Department of Surgery, Tsuyama Chuo Hospital Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Double-flap technique (DFT) is a reconstruction procedure after proximal gastrectomy (PG). We previously reported a multi-center, retrospective study in which the incidence of reflux esophagitis (RE) (Los Angeles Classification ≥Grade B [LA-B]) 1 year after surgery was 6.0%. There have been many reports, but all of them were retrospective. Thus, a multi-center, prospective study was conducted. Methods: Laparoscopic PG + DFT was performed for cT1N0 upper gastric cancer patients. The primary endpoint was the incidence of RE (≥LA-B) 1 year after surgery. The planned sample size was 40, based on an estimated incidence of 6.0% and an upper threshold of 20%. Results: Forty patients were recruited, and 39, excluding one with conversion to total gastrectomy, received protocol treatment. Anastomotic leakage (Clavien–Dindo ≥Grade III) was observed in one patient (2.6%). In 38 patients, excluding one case of postoperative mortality, RE (≥LA-B) was observed in two patients (5.3%) 1 year after surgery, and the upper limit of the 95% confidence interval was 17.3%, lower than the 20% threshold. Anastomotic stricture requiring dilatation was observed in two patients (5.3%). One year after surgery, body weight change was 88.9 ± 7.0%, and PNI <40 and CONUT ≥5, indicating malnutrition, were observed in only one patient (2.6%) each. In the quality of life survey using the PGSAS-45 questionnaire, the esophageal reflux subscale score was 1.4 ± 0.6, significantly better than the public data (2.0 ± 1.0; p = 0.001). Conclusion: Laparoscopic DFT showed anti-reflux efficacy. Taken together with the acceptable incidence of anastomotic stricture, DFT can be an option for reconstruction procedure after PG. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Is Proximal Triangular Fixation Better than the Conventional Method in Adult Spinal Deformity Surgery? 37 46 EN Masato Tanaka Department of Orthopaedic Surgery, Okayama Rosai Hospital Umesh Meena Department of Orthopaedic Surgery, Okayama Rosai Hospital Takuya Taoka Department of Orthopaedic Surgery, Okayama Rosai Hospital Yoshihiro Fujiwara Department of Orthopaedic Surgery, Okayama Rosai Hospital Daiichiro Yokomizo Department of Orthopaedic Surgery, Okayama Rosai Hospital Santosh Kumar Bashyal Department of Orthopaedic Surgery, Okayama Rosai Hospital Naveen Sake Department of Orthopaedic Surgery, Okayama Rosai Hospital Shinya Arataki Department of Orthopaedic Surgery, Okayama Rosai Hospital Original Article 10.18926/AMO/66669 In adult spinal deformity (ASD) surgery, one of the key factors working to prevent proximal junctional kyphosis is the proximal anchor. The aim of this study was to compare clinical and radiographic outcomes of triangular fixation with conventional fixation as proximal anchoring techniques in ASD surgery. We retrospectively evaluated 54 patients who underwent corrective spinal fusion for ASD. Fourteen patients underwent proximal triangular fixation (Group T; average 74.6 years), and 40 patients underwent the conventional method (Group C; average 70.5 years). Clinical and radiographic outcomes were assessed using visual analogue scale (VAS) values for back pain and the Oswestry disability index (ODI). Radiographic evaluation was also collected preoperatively and postoperatively. Surgical times and intraoperative blood loss of the two groups were not significantly different (493 vs 490 min, 1,260 vs 1,173 mL). Clinical outcomes such as VAS and ODI were comparable in the two groups. Proximal junctional kyphosis in group T was slightly lower than that of group C (28.5% vs 47.5%, p=0.491). However, based on radiology, proximal screw pullout occurred significantly less frequently in the triangular fixation group than the conventional group (0.0% vs 22.5%, p=0.049). Clinical outcomes in the two groups were not significantly different. 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 Instant estimation of rice yield using ground-based RGB images and its potential applicability to UAV 41 48 EN Yu Tanaka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tomoya Watanabe Graduate School of Mathematics, Kyushu University Keisuke Katsura Graduate School of Agriculture, Tokyo University of Agriculture and Technology Yasuhiro Tsujimoto Japan International Research Center for Agricultural Sciences Toshiyuki Takai Japan International Research Center for Agricultural Sciences Takashi Sonam Tashi Tanaka Faculty of Biological Sciences, Gifu UniversityFaculty of Biological Sciences, Gifu University Kensuke Kawamura Japan International Research Center for Agricultural Sciences Hiroki Saito Tropical Agriculture Research Front, Japan International Research Center for Agricultural Sciences Koki Homma Graduate School of Agricultural Science, Tohoku University Salifou Goube Mairoua Africa Rice Center （AfricaRice） Kokou Ahouanton Africa Rice Center （AfricaRice） Ali Ibrahim Africa Rice Center （AfricaRice）, Regional Station for the Sahel Kalimuthu Senthilkumar Africa Rice Center （AfricaRice） Vimal Kumar Semwal Africa Rice Center （AfricaRice）, Nigeria Station Eduardo Jose Graterol Matute Latin American Fund for Irrigated Rice - The Alliance of Bioversity International and CIAT Edgar Corredor Latin American Fund for Irrigated Rice - The Alliance of Bioversity International and CIAT Raafat El-Namaky Rice Research and Training Center, Field Crops Research Institute Norvie Manigbas Philippine Rice Research Institute （PhilRice） Eduardo Jimmy P. Quilang Philippine Rice Research Institute （PhilRice） Yu Iwahashi Graduate School of Agriculture, Kyoto University Kota Nakajima Graduate School of Agriculture, Kyoto University Eisuke Takeuchi Graduate School of Agriculture, Kyoto University Kazuki Saito Japan International Research Center for Agricultural Sciences Rice (Oryza sativa L.) is one of the most important cereals, which provides 20% of the world’s food energy. However, its productivity is poorly assessed especially in the global South. Here, we provide a first study to perform a deep learning-based approach for instantaneously estimating rice yield using RGB images. During ripening stage and at harvest, over 22,000 digital images were captured vertically downwards over the rice canopy from a distance of 0.8 to 0.9m at 4,820 harvesting plots having the yield of 0.1 to 16.1 t ha-1 across six countries in Africa and Japan. A convolutional neural network (CNN) applied to these data at harvest predicted 68% variation in yield with a relative root mean square error (rRMSE) of 0.22. Even when the resolution of images was reduced (from 0.2 to 3.2cm pixel-1 of ground sampling distance), the model could predict 57% variation in yield, implying that this approach can be scaled by use of unmanned aerial vehicles. Our work offers low-cost, hands-on, and rapid approach for high throughput phenotyping, and can lead to impact assessment of productivity-enhancing interventions, detection of fields where these are needed to sustainably increase crop production. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2352-409X 53 2024 Multi-isotopic analysis of domestic burials from sin Cabezas, Escuintla, Guatemala 104348 EN Shintaro Suzuki Research Institute for the Dynamics of Civilizations, Okayama University Tomás Barrientos Centro de Investigaciones Arqueológicas y Antropológicas, Universidad del Valle de Guatemala Héctor Mejía Transportadora de Energía de Centroamérica, Universidad de San Carlos de Guatemala T. Douglas Price University of Wisconsin We present the results from the stable isotope measurements of strontium (87Sr/86Sr) and oxygen (δ 18O) in tooth enamel from 36 individuals from the site of Sin Cabezas, Escuintla, Guatemala. This is the first contribution of isotopic proveniencing from the Pacific Coast of Guatemala and offers new solid baseline reference data from a large archaeological sample. Although some outlier cases are identified, the high homogeneity is the most evident feature in the sample. Based on this homogeneity, we discuss a critical issue of baseline data between Teotihuacan and the Pacific Coast, where the material culture has indicated intimate cultural interactions. A critical overlap for both strontium and oxygen reference between the Mexican metropolis and the coastal region is pointed out. This is why detecting human movement between both regions is still elusive. A case study of a possible Mexican individual is introduced. We also assess the outlier cases in terms of proveniencing and add several osteobiographic notes for the most relevant cases whose origin could be seen among the Northern - Eastern part of the Guatemalan Highlands, the Soconusco border region, or Central Honduras. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1758-8103 14 2 2023 Trends in childhood obesity in Japan: A nationwide observational study from 2012 to 2021 e12636 EN Shintaro Fujiwara Department of Pediatrics, NHO Okayama Medical Center Ko Harada Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshihiro Koyama Department of Pharmaceutical Biomedicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, 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 The persistent ascension of childhood obesity on a global scale constitutes a significant quandary. The prevalence of childhood obesity in Japan peaked in the early 2000s and has been reported to have declined since then, but recent data and its trend including the novel coronavirus disease 2019 (COVID-19) pandemic era are not available. Moreover, there is a dearth of studies examining the correlation between the trend in childhood obesity and exercise habits over the past decade. This study aims to examine the changes in the prevalence of obesity, physical fitness, and exercise habits over the past 10 years in Japanese children. We investigated the prevalence of childhood obesity in Japan, using the School Health Statistics Survey data from 2012 to 2021. The dataset has a sample size representative of children nationwide and includes variables for obesity, such as height, weight, and age. Data were classified into groups by sex and age (6–8, 9–11, and 12–14 years age). Children weighing 20% or more of the standard body weight are classified as obese. The annual percentage changes and average annual percentage changes were estimated using the joinpoint regression model. We also examined the trends in the physical fitness test score and exercise time. Average annual percentage changes of boys increased, especially in the 6- to 8-year age group (3.4%–4.6%). For girls, average annual percentage changes had increased in 6- to 8-year (2.5%–4.0%) and 9- to 11-year (0.9%–2.2%) age groups. Since the late 2010s, significantly increasing annual percentage changes were observed in 12- to 14-year age boys (6.7%–8.9%) and girls of many age groups (2.6%–8.6%). The physical fitness test score and exercise time showed decreasing trends since the late 2010s. Childhood obesity may have generally risen in Japan, in the last decade. Encouraging healthy eating and physical activity through school policies and curricula is necessary. No potential conflict of interest relevant to this article was reported.

American Society of Hematology Acta Medica Okayama 2473-9529 7 24 2023 Distribution and clinical impact of molecular subtypes with dark zone signature of DLBCL in a Japanese real-world study 7459 7470 EN Tomohiro Urata Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Naoi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aixiang Jiang British Columbia Cancer, Centre for Lymphoid Cancer Merrill Boyle British Columbia Cancer, Centre for Lymphoid Cancer Kazutaka Sunami Department of Hematology, NHO Okayama Medical Center Toshi Imai Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Yuichiro Nawa Division of Hematology, Ehime Prefectural Central Hospital Yasushi Hiramatsu Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital Kazuhiko Yamamoto Department of Hematology and Oncology, Okayama City Hospital Soichiro Fujii Department of Hematology, Japanese Red Cross Okayama Hospital Isao Yoshida Department of Hematologic Oncology, NHO Shikoku Cancer Center Tomofumi Yano Department of Internal Medicine, Okayama Rosai Hospital Ryota Chijimatsu Center for Comprehensive Genomic Medicine, Okayama University Hospital Hiroyuki Murakami Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Ikeuchi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Kobayashi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuma Tani Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideki Ujiie Center for Comprehensive Genomic Medicine, Okayama University Hospital Hirofumi Inoue Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Akira Yamamoto Department of Hematology and Oncology, Okayama University Hospital Takumi Kondo Department of Hematology and Oncology, Okayama University Hospital Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Hospital Keisuke Sawada Department of Pathology, Saitama Medical Center, Saitama Medical University Shuji Momose Department of Pathology, Saitama Medical Center, Saitama Medical University Jun-ichi Tamaru Department of Pathology, Saitama Medical Center, Saitama Medical University Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Tadashi Yoshino Department of Pathology, Okayama University Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences David W. Scott British Columbia Cancer, Centre for Lymphoid Cancer Daisuke Ennishi Department of Hematology and Oncology, Okayama University Hospital The distribution and clinical impact of cell-of-origin (COO) subtypes of diffuse large B-cell lymphoma (DLBCL) outside Western countries remain unknown. Recent literature also suggests that there is an additional COO subtype associated with the germinal center dark zone (DZ) that warrants wider validation to generalize clinical relevance. Here, we assembled a cohort of Japanese patients with untreated DLBCL and determined the refined COO subtypes, which include the DZ signature (DZsig), using the NanoString DLBCL90 assay. To compare the distribution and clinical characteristics of the molecular subtypes, we used a data set from the cohort of British Columbia Cancer (BCC) (n = 804). Through the 1050 patient samples on which DLBCL90 assay was successfully performed in our cohort, 35%, 45%, and 6% of patients were identified to have germinal center B-cell–like (GCB) DLBCL, activated B-cell–like (ABC) DLBCL, and DZsig-positive (DZsigpos) DLBCL, respectively, with the highest prevalence of ABC-DLBCL, differing significantly from the BCC result (P < .001). GCB-DLBCL, ABC-DLBCL, and DZsigpos-DLBCL were associated with 2-year overall survival rates of 88%, 75%, and 66%, respectively (P < .0001), with patients with DZsigpos-DLBCL having the poorest prognosis. In contrast, GCB-DLBCL without DZsig showed excellent outcomes after rituximab-containing immunochemotherapy. DZsigpos-DLBCL was associated with the significant enrichment of tumors with CD10 expression, concurrent MYC/BCL2 expression, and depletion of microenvironmental components (all, P < .05). These results provide evidence of the distinct distribution of clinically relevant molecular subtypes in Japanese DLBCL and that refined COO, as measured by the DLBCL90 assay, is a robust prognostic biomarker that is consistent across geographical areas. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2590-0595 5 12 2023 Kidney Veno-Muscular Characteristics and Kidney Disease Progression: A Native Kidney-Biopsy Study 100733 EN Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kensaku Takahashi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Takafumi Morita Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yizhen Sang Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Natsumi Matsuoka-Uchiyama 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 Haruhito A. Uchida Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kitamura 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 Rationale & Objective: Assessment of kidney biopsies provides crucial information for diagnosis and disease activity, as well as prognostic value. Kidney-biopsy specimens occasionally contain veno-muscular complex (VMC), which consists of muscle tissues around the kidney venous system in the corticomedullary region. However, the role of VMC and the clinical significance of VMC variants are poorly understood. In the present study, we investigated kidney prognostic values of VMC variants. Study Design: Retrospective cohort study. Setting & Participants: Among 808 patients who underwent a kidney biopsy from 2011 to 2019, 246 patients whose kidney biopsy specimens contained VMC were enrolled. Predictors: VMC variants; inflammatory-VMC (an infiltration of ≥80 inflammatory cells/mm2-VMC area) and VMC hypertrophy (hyper-VMC, a VMC average width ≥850 μm), and the interstitial fibrosis/tubular atrophy (IFTA) score. Outcomes: A decline in estimated glomerular filtration rate (eGFR) ≥40% from the baseline or commencement of kidney replacement therapy. Analytical Approach: Cox proportional hazards model. Results: Among 246 patients with data on VMC, mean baseline eGFR was 56.0±25.6 ml/min per 1.73 m2; 80 had high inflammatory-VMC, and 62 had VMC hypertrophy. There were 51 kidney events over median follow-up of 2.5 years. We analyzed 2 VMC variants. Multivariable logistic regression analysis revealed that eGFR negatively correlated with the presence of both inflammatory-VMC and hyper-VMC. A Cox proportional hazards analysis revealed that inflammatory-VMC (but not hyper-VMC) was independently associated with the primary outcome after adjustments for known risk factors of progression, including proteinuria, eGFR, and the interstitial fibrosis/tubular atrophy (IFTA) score (hazard ratio, 1.97; 95% confidence interval, 1.00-3.91). Limitations: Single-center study and small sample size. Conclusions: Assessment of inflammatory-VMC provides additional kidney prognostic information to known indicators of kidney disease progression in patients who undergo kidney biopsy. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0003-2670 1278 2023 Determination of mass-dependent chromium isotopic compositions in geological samples by double spike-total evaporation-thermal ionization mass spectrometry (DS-TE-TIMS) 341723 EN Dilan M. Ratnayake The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Ryoji Tanaka The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Eizo Nakamura The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Background: Chromium isotopes have been used to trace geochemical and cosmochemical processes in the past. However, the presence of multivalent Cr species has made it difficult to isolate Cr from geological samples, particularly for samples with a low Cr mass fraction. Results: Here, a simple three-step ion exchange chromatography procedure is presented to separate Cr from various sample matrices, ranging from ultramafic to felsic rocks. Throughout each of the column chromatography step, 1 mL of cation exchange resin AG50W-X8 (200–400 mesh) was used as the stationary phase and oxalic acid as a chelating agent, was used in addition to the inorganic acids. This method yielded high recoveries of Cr [93 ± 8% (2SD, N = 7)] regardless of the lithology. The total procedural blank of Cr was <0.5 ng. We also developed a double spike-total evaporation-thermal ionization mass spectrometry (DS-TE-TIMS) technique that significantly reduced sample consumption to ∼20 ng of Cr per each measurement of mass-dependent 53Cr/52Cr. Significance: This study achieved a 2SD external precision of 0.02‰ for the analysis of NIST NBS3112a and of 0.01–0.07‰ for the geological samples. This study enabled high-precision Cr isotope analysis in geological samples with various matrix and Cr compositions using relatively small sample volumes. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2666-3643 4 10 2023 Immunologic Significance of CD80/CD86 or Major Histocompatibility Complex-II Expression in Thymic Epithelial Tumors 100573 EN Hideki Ikeda Chiba Cancer Center, Research Institute Joji Nagasaki Chiba Cancer Center, Research Institute Daiki Shimizu Division of Thoracic Surgery, Chiba Cancer Center Yuki Katsuya Department of Experimental Therapeutics, National Cancer Center Hospital Hidehito Horinouchi Department of Thoracic Oncology, National Cancer Center Hospital Yukio Hosomi Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Etsuko Tanji Chiba Cancer Center, Research Institute Takekazu Iwata Division of Thoracic Surgery, Chiba Cancer Center Makiko Itami Department of Surgical Pathology, Chiba Cancer Center Masahito Kawazu Chiba Cancer Center, Research Institute Yuichiro Ohe Department of Thoracic Oncology, National Cancer Center Hospital Takuji Suzuki Department of Respirology, Graduate School of Medicine, Chiba University Yosuke Togashi Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Introduction: Unresectable or recurrent thymic epithelial tumors (TETs) have a poor prognosis, and treatment options are limited. This study aimed to investigate the immunologic significance of CD80/CD86 or major histocompatibility complex class II (MHC-II) expression in TETs, as potential predictive biomarkers for immune checkpoint inhibitors (ICIs). Methods: We analyzed CD80, CD86, MHC class I (MHC-I), and MHC-II expression in TETs using immunohistochemistry and investigated their association with T-cell infiltration or ICI efficacy. In addition, we generated CD80- or MHC-II–expressing mouse tumors, evaluated the effects of ICIs, and analyzed tumor-infiltrating lymphocytes. We also performed tumor-rechallenge experiments in vivo. Results: We found that approximately 50% and 30% of TETs had high expression of CD80/CD86 and MHC-II in tumor cells, respectively, and that this expression was related to T-cell infiltration in clinical samples. In mouse models, both CD80 and MHC-II increase the effects of ICIs. In addition, senescent T cells and long-lived memory precursor effector T cells were significantly decreased and increased, respectively, in tumor-infiltrating lymphocytes from CD80-expressing tumors, and rechallenged tumors were completely rejected after the initial eradication of CD80-expressing tumors by programmed cell death protein 1 blockade. Indeed, patients with CD80-high thymic carcinoma had longer progression-free survival with anti–programmed cell death protein 1 monoclonal antibody. Conclusions: Half of the TETs had high expression of CD80/CD86 or MHC-II with high T-cell infiltration. These molecules could potentially increase the effects of ICIs, particularly inducing a durable response. CD80/CD86 and MHC-II can be predictive biomarkers of ICIs in TETs, promoting the development of drugs for such TETs. No potential conflict of interest relevant to this article was reported.

American Association for the Advancement of Science (AAAS) Acta Medica Okayama 2643-6515 5 2023 Deep Learning Enables Instant and Versatile Estimation of Rice Yield Using Ground-Based RGB Images 0073 EN Yu Tanaka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tomoya Watanabe Graduate School of Mathematics, Kyushu University Keisuke Katsura Graduate School of Agriculture, Tokyo University of Agriculture and Technology Yasuhiro Tsujimoto Japan International Research Center for Agricultural Sciences Toshiyuki Takai Japan International Research Center for Agricultural Sciences Takashi Sonam Tashi Tanaka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kensuke Kawamura Japan International Research Center for Agricultural Sciences Hiroki Saito Tropical Agriculture Research Front, Japan International Research Center for Agricultural Sciences Koki Homma Graduate School of Agricultural Science, Tohoku University Salifou Goube Mairoua Africa Rice Center (AfricaRice) Kokou Ahouanton Africa Rice Center (AfricaRice) Ali Ibrahim Africa Rice Center (AfricaRice), Regional Station for the Sahel Kalimuthu Senthilkumar Africa Rice Center (AfricaRice) Vimal Kumar Semwal Africa Rice Center (AfricaRice), Nigeria Station Eduardo Jose Graterol Matute Latin American Fund for Irrigated Rice - The Alliance of Bioversity International and CIAT Edgar Corredor Latin American Fund for Irrigated Rice - The Alliance of Bioversity International and CIAT Raafat El-Namaky Rice Research and Training Center, Field Crops Research Institute, ARC Norvie Manigbas Philippine Rice Research Institute (PhilRice) Eduardo Jimmy P. Quilang Philippine Rice Research Institute (PhilRice) Yu Iwahashi Graduate School of Agriculture, Kyoto University Kota Nakajima Graduate School of Agriculture, Kyoto University Eisuke Takeuchi Graduate School of Agriculture, Kyoto University Kazuki Saito Graduate School of Agriculture, Kyoto University Rice (Oryza sativa L.) is one of the most important cereals, which provides 20% of the world’s food energy. However, its productivity is poorly assessed especially in the global South. Here, we provide a first study to perform a deep-learning-based approach for instantaneously estimating rice yield using red-green-blue images. During ripening stage and at harvest, over 22,000 digital images were captured vertically downward over the rice canopy from a distance of 0.8 to 0.9 m at 4,820 harvesting plots having the yield of 0.1 to 16.1 t·ha−1 across 6 countries in Africa and Japan. A convolutional neural network applied to these data at harvest predicted 68% variation in yield with a relative root mean square error of 0.22. The developed model successfully detected genotypic difference and impact of agronomic interventions on yield in the independent dataset. The model also demonstrated robustness against the images acquired at different shooting angles up to 30° from right angle, diverse light environments, and shooting date during late ripening stage. Even when the resolution of images was reduced (from 0.2 to 3.2 cm·pixel−1 of ground sampling distance), the model could predict 57% variation in yield, implying that this approach can be scaled by the use of unmanned aerial vehicles. Our work offers low-cost, hands-on, and rapid approach for high-throughput phenotyping and can lead to impact assessment of productivity-enhancing interventions, detection of fields where these are needed to sustainably increase crop production, and yield forecast at several weeks before harvesting. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 0737-3937 42 2 2023 Flavor retention characteristics of amorphous solid dispersion of flavors, prepared by vacuum-foam- and spray-drying under different conditions 227 237 EN Yuna Nitta Department of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Haruna Sato Department of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Rina Yamamoto Department of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Hiroyuki Imanaka Department of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Naoyuki Ishida Department of Chemical Engineering and Material Sciences, Faculty of Science and Engineering, Doshisha University Koreyoshi Imamura Department of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University We investigated the powderization of flavoring substances, using an amorphous solid dispersion (ASD) technique, in which hydrophobic molecules are separately embedded in a water-soluble carrier matrix. Six flavors, five carrier forming materials (polyvinylpyrrolidone/disaccharides), two solvents (methanol/ethanol) and two drying methods (vacuum-foam-/spray-drying) were employed. The drying conditions for the two drying processes were first examined, and under the optimal drying conditions, various flavor-carrier combinations and compositions of ASD samples were prepared and their flavor retention after drying and during storage under a vacuum were compared. Results demonstrated that flavor loss during drying and storage was minimized when the material was vacuum-foam-dried with polyvinylpyrrolidone. Vacuum-foam-drying in the presence of α-maltose or palatinose also resulted in a greater retention of flavor during drying and storage than a typical O/W emulsification-based powderization. These findings suggest that the ASD-based powderization of flavoring materials is a feasible alternative to the currently used produces. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Effects of Nutritional Support Combined with Neuromuscular Electrical Stimulation on Muscle Strength and Thickness: A Randomized Controlled Trial in Healthy Young Adult Males 635 645 EN Tomohiro Ikeda Department of Rehabilitation Medicine, Okayama University Hospital Kazunori Okamura Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Masaki Hasegawa Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Satoshi Tanaka Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Shusaku Kanai Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Original Article 10.18926/AMO/66156 In the management of post-injury patients with activity limitations, methods to prevent musculoskeletal disorders and hasten recovery are important. This randomized controlled, single-blinded study was a preliminary investigation of the combined effect of nutritional support with neuromuscular electrical stimulation (NMES) on muscle strength and thickness. Healthy young adult males (median age, 21 years) were enrolled; each of their hands was randomly assigned to one of the following four groups: Placebo, Nutrition, NMES, and Nutrition + NMES. All participants received whey protein or placebo (3x/week for 6 weeks) and NMES training (3x/week for 6 weeks) on the abductor digiti minimi (ADM) muscle of either the left or right hand. ADM muscle strength and thickness were analyzed at baseline and at week 7. We analyzed 38 hands (9 Placebo, 10 Nutrition, 9 NMES, 10 Nutrition + NMES). There was significantly greater muscle strengthening in the Nutrition + NMES group compared to the Placebo group or the NMES group, but no significant difference in gain of muscle thickness. The combined intervention may be effective in improving muscle strength. Future clinical trials targeting various muscles after sports-related injuries are warranted. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 2169-9313 127 3 2022 Deformation of Post‐Spinel Under the Lower Mantle Conditions e2021JB023586 EN F. Xu Institute for Planetary Materials, Okayama University D. Yamazaki Institute for Planetary Materials, Okayama University S. A. Hunt Department of Earth Sciences, University College London N. Tsujino Institute for Planetary Materials, Okayama University Y. Higo Japan Synchrotron Radiation Research Institute Y. Tange Japan Synchrotron Radiation Research Institute K. Ohara Japan Synchrotron Radiation Research Institute D. P. Dobson Department of Earth Sciences, University College London To study the viscosity of bridgmanite and ferropericlase aggregate, uniaxial compression deformation experiments on pre-synthesized post-spinel phase and bridgmanite two-layered samples were conducted under top lower mantle pressure and 1773 K utilizing DT-Cup apparatus. Up to the strain of 0.25 ± 0.05, the observed comparable strain of the bridgmanite and post-spinel samples suggests the bridgmanite dominates the bulk viscosity of the post-spinel without strain localization in periclase. The microstructures of the deformed post-spinel samples show evidence of a similar strain of periclase with the bulk strain without strain partitioning. Texture analyses of bridgmanite indicate a dominant slip plane (100), with a steady state fabric strength achieved within the strain of 0.12 ± 0.01. The current experiment has provided no evidence about an onset of strain localization of ∼30 vol.% periclase at 0.25 strain. Our observations provide direct experimental verification of bridgmanite controlled rheology under low strain magnitude, which should be considered in geodynamical models which include mantle compositional and rheological evolution in the lower mantle. 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.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Endoscopic Manifestations and Clinical Characteristics of Localized Gastric Light-Chain Amyloidosis 545 552 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shouichi Tanaka Department of Gastroenterology, National Hospital Organization Iwakuni Clinical Center Tatsuya Toyokawa Department of Gastroenterology, National Hospital Organization Fukuyama Medical Center Mamoru Nishimura Department of Internal Medicine, Okayama City Hospital Takao Tsuzuki Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital Koji Miyahara Department of Internal Medicine, Hiroshima City Hiroshima Citizens Hospital Shin Negishi Department of Gastroenterology, Kagawa Prefectural Central Hospital Shogen Ohya Kawaguchi Medical Clinic Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65978 To determine the endoscopic and clinical features of localized gastric amyloid light-chain (AL) amyloidosis, we retrospectively examined the characteristics of nine patients (eight men and one woman) encountered by the hospitals in our network. Lesions were predominantly flat and depressed with surface vascular dilatation (n=5); others were characterized by subepithelial lesions (n=2), mucosal color change (n=1), and a mass-like morphology with swollen mucosal folds (n=1). Colonoscopy (n=7), video capsule enteroscopy (n=2), serum (n=5) and urine immunoelectrophoresis (n=4), and bone marrow examination (n=3) were performed to exclude involvement of organs other than the stomach. As treatment for gastric lesions of AL amyloidosis, one patient each underwent endoscopic submucosal dissection (n=1) and argon plasma coagulation (n=1), while the remaining seven patients underwent no specific treatment. During a mean follow-up of 4.2 years, one patient died 3.2 years after diagnosis, but the cause of death, which occurred in another hospital, was unknown. The remaining eight patients were alive at the last visit. In conclusion, although localized gastric AL amyloidosis can show various macroscopic features on esophagogastroduodenoscopy, flat, depressed lesions with vascular dilatation on the surface are predominant. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 2046-2069 12 6 2022 Flame retardance-donated lignocellulose nanofibers (LCNFs) by the Mannich reaction with (amino-1,3,5-triazinyl)phosphoramidates and their properties 3300 3308 EN Fumiaki Ono Okayama Biomass Innovation Creative Center Takumi Okihara Graduate School of Natural Science and Technology, Okayama University Noboru Osaka Faculty of Science, Okayama University of Science Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Science, Okayama University Dental School Yuji Kameoka Marubishi Oil Chemical Co., Ltd Akira Ishikawa Marubishi Oil Chemical Co., Ltd Hironari Ooki Gen Gen Corporation Takumi Ito Gen Gen Corporation Daisuke Todome Faculty of Science, Okayama University of Science Shinya Uemoto Okayama Biomass Innovation Creative Center Mitsuaki Furutani Okayama Biomass Innovation Creative Center Tsutomu Inokuchi Graduate School of Natural Science and Technology, Okayama University Kenji Okada Department of Life Science, Kurashiki University of Science & the Arts Nitrogen/phosphorus-containing melamines (NPCM), a durable flame-retardant, were prepared by the successive treatment of ArOH (Ar = BrnC6H5−n, n = 0, 1, 2, and 3) with POCl3 and melamine monomer. The prepared flame-retardants were grafted through the CH2 unit to lignocellulose nanofibers (LCNFs) by the Mannich reaction. The resulting three-component products were characterized using FT-IR (ATR) and EA. The thermal behavior of the NPCM-treated LCNF fabric samples was determined using TGA and DSC analyses, and their flammability resistances were evaluated by measuring their Limited Oxygen Index (LOI) and the UL-94V test. A multitude of flame retardant elements in the fabric samples increased the LOI values as much as 45 from 20 of the untreated LCNFs. Moreover, the morphology of both the NPCM-treated LCNFs and their burnt fabrics was studied with a scanning electron microscope (SEM). The heat release lowering effect of the LCNF fabric against the water-based paint was observed with a cone calorimeter. Furthermore, the mechanical properties represented as the tensile strength of the NPCM-treated LCNF fabrics revealed that the increase of the NPCM content in the PP-composites led to an increased bending strength with enhancing the flame-retardance. No potential conflict of interest relevant to this article was reported.

Spandidos Publications Acta Medica Okayama 1792-1074 24 4 2022 Effect of bacterium in the malignant wounds of soft tissue sarcoma 345 EN Eiji Nakata Department of Orthopedic Surgery, Okayama University Hospital Tomohiro Fujiwara Department of Orthopedic Surgery, Okayama University Hospital Haruyoshi Katayama Department of Orthopedic Surgery, Okayama University Hospital Takuto Itano Department of Orthopedic Surgery, Okayama University Hospital Toshiyuki Kunisada Department of Orthopedic Surgery, Okayama University Hospital Toshifumi Ozaki Department of Orthopedic Surgery, Okayama University Hospital Malignant wounds (MWs) are rare skin lesions, which accompany ulceration, necrosis and infection caused by infiltration or damage by malignant tumor. The present study aimed to investigate the bacterial etiology implicated in MW in soft tissue sarcoma (STS), and the effectiveness of culture‑guided perioperative antibacterial administration. A retrospective evaluation was conducted on medical records of patients who presented with MW between 2006 and 2020. A total of seven patients were included in the present study, in whom all tumors were relatively large (>5 cm) and high‑grade. Subsequently, five patients underwent limb‑sparing surgery, and three patients had distant metastases with a 5‑year overall survival of 71%. Preoperative microbiological sampling from the wound identified 11 different bacterial strains in five patients. The infections were polymicrobial with an average of 2.6 strains isolated per patient (1 aerobic, 1.6 anaerobic bacteria). They were predominantly methicillin‑sensitive Staphylococcus aureus. Patients with MWs from STS reported symptoms, including bleeding (71%), exudation (71%) and malodorous wound (43%) at the initial presentation; these completely resolved after surgery. All but one patient reported pain at the MW site with an average numeric rating scale of 4.4 at presentation that decreased to 1.4 (P=0.14) and 0.6 (P=0.04) one and two weeks after surgery, respectively. The patients had elevated C‑reactive protein (71%), anemia (57%), low albumin (86%) and renal/liver dysfunction (14‑29%). One patient was diagnosed with sepsis. Surgical resection afforded symptomatic relief and resolution of abnormal laboratory values. Although selected antibiotics were administered in four patients based on the preoperative antibiotic sensitivity test, surgical site infection (SSI) occurred in three patients. Therefore, the effectiveness of the selected antibiotics based on the results of the preoperative culture in preventing SSI needs to be investigated in the future. In conclusion, physicians should keep in mind that although surgical resection can improve the symptoms and abnormal values in laboratory examination form MW, it is accompanied with a high rate of SSI and poor prognosis. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1091-255X 26 6 2022 Diagnostic Utility of the PD-L1 Immunostaining in Biopsy Specimens of Patients with Biliary Tract Neoplasms 1213 1223 EN Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiaki Ohara Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akinobu Takaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masahiro Takahara Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryuichi Yoshida Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takahito Yagi Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akihiro Matsukawa Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background　Anti-programmed death 1/programmed death ligand 1 (PD1/PD-L1) antibodies have been successfully used as treatment agents for several solid tumors; however, it is difficult to predict their effectiveness. We evaluated whether biopsy specimens could predict the positive status of PD-L1 in surgically resected tissue. Methods　Among 91 patients who underwent tissue sampling with endoscopic or liver biopsy before surgery for biliary tract neoplasms in an academic center, 45 (49%) patients were selected for retrospective analysis because the quality and quantity of their biopsy specimens were adequate for histologic evaluation. We performed immunohistochemical staining to investigate the PD-L1 expression in both resected and biopsy specimens. The percentage of the positively stained cells was calculated for subsequent use in the correlation investigation. Results　The biopsy methods were endoscopic retrograde cholangiopancreatography (ERCP) in 28 cases, percutaneous liver biopsy in 10 cases, and endoscopic ultrasound fine-needle aspiration in 7 cases. Among the 45 patients, when patients with > 10% positive tumor cells in surgically resected tissues were regarded as truly positive PD-L1, the positive and negative concordance rates between surgically resected tissues and biopsy samples were 56% (5/9) and 100% (36/36), respectively. With regard to the use of preoperative biopsy as a diagnostic tool, all (5/5) PD-L1-positive patients had a positive resected specimen. The accuracy of each biopsy method was as follows: ERCP, 89% (25/28); fine-needle aspiration, 86% (6/7); and liver biopsy, 100% (10/10). Conclusions　Biopsy samples could be a surrogate material for the assessment of the PD-L1 expression with substantial positive and high negative concordance rates. No potential conflict of interest relevant to this article was reported.

American Association for Cancer Research Acta Medica Okayama 2767-9764 2 7 2022 Mixed Response to Cancer Immunotherapy is Driven by Intratumor Heterogeneity and Differential Interlesion Immune Infiltration 739 753 EN Takao Morinaga Chiba Cancer Center, Research Institute Takashi Inozume Chiba Cancer Center, Research Institute Masahito Kawazu Chiba Cancer Center, Research Institute Youki Ueda Department of Tumor Microenvironment, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Nicolas Sax KOTAI Biotechnologies Inc Kazuo Yamashita KOTAI Biotechnologies Inc Shusuke Kawashima Chiba Cancer Center, Research Institute Joji Nagasaki Department of Tumor Microenvironment, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Toshihide Ueno Division of Cellular Signaling, National Cancer Center Research Institute Jason Lin Chiba Cancer Center, Research Institute Yuuki Ohara Department of Pathology, National Cancer Center Hospital East Takeshi Kuwata Department of Genetic Medicineand Services, National Cancer Center Hospital East Hiroki Yukami Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East Akihito Kawazoe Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East Kohei Shitara Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East Akiko Honobe-Tabuchi Department of Dermatology, University of Yamanashi Takehiro Ohnuma Department of Dermatology, University of Yamanashi Tatsuyoshi Kawamura Department of Dermatology, University of Yamanashi Yoshiyasu Umeda Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center Yu Kawahara Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center Yasuhiro Nakamura Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center Yukiko Kiniwa Department of Dermatology, Shinshu University School of Medicine Ayako Morita Department of Allergy and Respiratory Medicine, Okayama University Hospital Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Tomohiro Enokida Department of Head and Neck Medical Oncology, National Cancer Center Hospital East Makoto Tahara Department of Head and Neck Medical Oncology, National Cancer Center Hospital East Yoshinori Hasegawa Department of Applied Genomics, Kazusa DNA Research Institute Hiroyuki Mano Division of Cellular Signaling, National Cancer Center Research Institute Yutaka Suzuki Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo Hiroyoshi Nishikawa Division of Cancer Immunology, Research Institute/Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center Yosuke Togashi Department of Tumor Microenvironment, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Some patients experience mixed response to immunotherapy, whose biological mechanisms and clinical impact have been obscure. We obtained two tumor samples from lymph node (LN) metastatic lesions in a same patient. Whole exome sequencing for the both tumors and single-cell sequencing for the both tumor-infiltrating lymphocytes (TIL) demonstrated a significant difference in tumor clonality and TILs' characteristics, especially exhausted T-cell clonotypes, although a close relationship between the tumor cell and T-cell clones were observed as a response of an overlapped exhausted T-cell clone to an overlapped neoantigen. To mimic the clinical setting, we generated a mouse model of several clones from a same tumor cell line. Similarly, differential tumor clones harbored distinct TILs, and one responded to programmed cell death protein 1 (PD-1) blockade but the other did not in this model. We further conducted cohort study (n = 503) treated with PD-1 blockade monotherapies to investigate the outcome of mixed response. Patients with mixed responses to PD-1 blockade had a poor prognosis in our cohort. Particularly, there were significant differences in both tumor and T-cell clones between the primary and LN lesions in a patient who experienced tumor response to anti-PD-1 mAb followed by disease progression in only LN metastasis. Our results underscore that intertumoral heterogeneity alters characteristics of TILs even in the same patient, leading to mixed response to immunotherapy and significant difference in the outcome. Significance: Several patients experience mixed responses to immunotherapies, but the biological mechanisms and clinical significance remain unclear. Our results from clinical and mouse studies underscore that intertumoral heterogeneity alters characteristics of TILs even in the same patient, leading to mixed response to immunotherapy and significant difference in the outcome. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0021-9673 1706 2023 Separation and fractionation of glutamic acid and histidine via origami isoelectric focusing 464247 EN Kaewta Danchana Department of Chemistry, Okayama University Nayu Yamashita Department of Chemistry, Okayama University Mika I. Umeda Department of Chemistry, Okayama University Takashi Kaneta Department of Chemistry, Okayama University We demonstrated the fractionation of two amino acids, glutamic acid and histidine, separated via isoelectric focusing (IEF) on filter paper folded and stacked in an origami fashion. Channels for electrophoresis were fabricated as circular zones acquired via wax printing onto the filter paper. An ampholyte solution with amphiphilic samples was deposited on all the circle zones, which was followed by folding to form the electrophoresis channels. IEF was achieved by applying an electrical potential between the anodic and cathodic chambers filled with phosphoric acid and sodium hydroxide solutions, respectively. A pH gradient was formed using either a wide-range ampholyte with a pH of 3 to 10 or a narrow-range version with a pH of 5 to 8, which was confirmed by adding pH indicators to each layer. The origami IEF was used to separate the amino acids, glutamic acid and histidine, by mixing with the ampholytes, which were deposited on the layers. The components in each layer were extracted with water and measured by high-performance liquid chromatography using pre-column derivatization with dansyl chloride. The results indicated that the focus for glutamic acid and that for histidine were at different layers, according to their isoelectric points. The origami isoelectric focusing achieved the fractionation of amino acids in less than 3 min using voltage as low as 30 V. No potential conflict of interest relevant to this article was reported.

The Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 62 16 2023 Cryptococcal Meningitis Developing in a Patient with Neurosarcoidosis 2433 2435 EN Shinnosuke Fukushima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukichika Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Oguni Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kou Hasegawa 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 Cryptococcal meningitis is a critical disease that occasionally involves immunosuppressed patients. We herein report a 79-year-old Japanese man who received low-dose prednisolone therapy for neurosarcoidosis and panhypopituitarism. He presented a 10-day history of a fever and altered mental status. The FilmArray & REG; Meningitis/Encephalitis Panel and serum cryptococcal antigen tests were both negative, but the cerebrospinal fluid sample became positive for Cryptococcus neoformans after seven-day incubation. After the diagnosis of cryptococcal meningitis, we successfully treated the patient with a recommended treatment regimen. When an immunocompromised patient presents with a subacute fever accompanying any central nervous symptoms, cryptococcal meningitis should be screened for. 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.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 Feasibility of Flow Cytometry Analysis of Gastrointestinal Tract-Residing Lymphocytes in Hematopoietic Stem Cell Transplant Recipients 347 357 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takumi Kondo Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Ennishi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuharu Fujii Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahide Takahashi Division of Medical Support, Okayama University Hospital Araki Hirabata Division of Medical Support, Okayama University Hospital Takehiro Tanaka Department of Pathology, 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 Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65740 The feasibility of lymphocyte isolation and flow cytometry using a single endoscopic biopsy specimen from the gastrointestinal tract of patients who have undergone hematopoietic stem cell transplantation has not been investigated. We acquired 51 endoscopic biopsy specimens from the gastrointestinal tract of 35 patients. We divided the flow cytometry samples into two groups: group A, successful lymphocyte isolation (n=24), and group B, incomplete isolation (n=27). We compared the backgrounds of the samples between the groups to reveal crucial elements in the successful isolation of lymphocytes residing in the gastrointestinal tract. Comparison between the groups revealed lymphocyte isolation success rates differed between biopsy sites. Isolation was most successful in samples from the duodenum (8/9, 88.9%), followed by the ileum (4/8, 50.0%), large intestine (4/11, 36.4%), and stomach (8/23, 34.8%). Tacrolimus was used more frequently in group B (92.6%) than in group A (62.5%) (p=0.015). Logistic regression analysis revealed that isolation from the duodenum or ileum was a significant factor for successful isolation, while tacrolimus use was not statistically significant. In conclusion, the duodenum and ileum are more suitable sites than the stomach and colorectum for acquiring samples for flow cytometry. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 2624-9553 4 2022 Sea Surface Temperature and Salinity in Lombok Strait Reconstructed From Coral Sr/Ca and δ18O, 1962–2012 918273 EN Ai Genda Graduate School of Natural Science and Technology, Okayama University Minoru Ikehara Center for Advanced Marine Core Research, Kochi University Atsushi Suzuki Geological Survey of Japan, National Institute of Advanced Industrial Science and Technology (AIST) Ali Arman Research and Technology Center for Application of Isotope and Radiation, National Research and Innovation Agency Mayuri Inoue Graduate School of Natural Science and Technology, Okayama University Coral geochemical tracers have been used in studies of the paleoclimatology and paleoceanography of the tropics and subtropics. We measured Sr/Ca and oxygen isotope ratios (δ18O) in a coral sample collected from the southern part of Lombok Strait, a significant outlet of the Indonesian Throughflow (ITF) to the Indian Ocean, to reconstruct the historical record of sea surface temperature (SST) and seawater δ18O. Seawater δ18O can be used to approximate sea surface salinity (SSS) because it reflects the balance of evaporation and precipitation. The resulting time series reconstructed SST and SSS, covering the period 1962–2012, shows no clear trend of global warming, although the record includes a large cooling event (~4°C) during 1996–1997. Although neither SST nor SSS shows a systematic relationship with El Niño–Southern Oscillation and Indian Ocean Dipole (IOD), weak but significant correlations are found partly. In addition, the coral data show signals of major IOD and El Niño events in 1994 and 1997, respectively, although climatic trends recorded in the coral are not consistent with those found along the Java-Sumatra coast. To evaluate other influences on the ITF in Lombok Strait, we compared our coral record with coral records from sites in the Java Sea, the southern part of Makassar Strait, and Ombai Strait. During the northwest monsoon (December–January–February), variations in SST and SSS at Lombok Strait site are similar to those at the Java Sea and southern Makassar sites for the period 1962–1995, which suggests that low-salinity water from the Java Sea is carried at least to the southern part of Makassar Strait where it suppresses the ITF upstream from Lombok Strait. However, the SST and SSS records differ at the three sites during the southeast monsoon (June–July–August), indicating that surface conditions in Lombok Strait vary separately from those in the Java Sea. In the longer term, although global warming has been widely identified in the Indonesian Seas, the coral record shows no clear warming trend in the southern part of Lombok Strait, where fluctuations in the ITF may be modulating the distribution of heat in the surface waters of the western Pacific and eastern Indian Ocean. 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.

Nature Portfolio Acta Medica Okayama 2045-2322 13 1 2023 ADAR1 is a promising risk stratification biomarker of remnant liver recurrence after hepatic metastasectomy for colorectal cancer 2078 EN Nanako Hata Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shuya Yano Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Sho Takeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hibiki Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiaki Takahashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshitaka Kondo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Kishimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshiko Mori 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 Hideki Yamamoto Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Michiue Neutron Therapy Research Center, Okayama University Keiichiro Nakamura Department of Obstetrics and Gynecology, 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 Adenosine-to-inosine RNA editing is a process mediated by adenosine deaminases that act on the RNA (ADAR) gene family. It has been discovered recently as an epigenetic modification dysregulated in human cancers. However, the clinical significance of RNA editing in patients with liver metastasis from colorectal cancer (CRC) remains unclear. The current study aimed to systematically and comprehensively investigate the significance of adenosine deaminase acting on RNA 1 (ADAR1) expression status in 83 liver metastatic tissue samples collected from 36 patients with CRC. The ADAR1 expression level was significantly elevated in liver metastatic tissue samples obtained from patients with right-sided, synchronous, or RAS mutant-type CRC. ADAR1-high liver metastasis was significantly correlated with remnant liver recurrence after hepatic metastasectomy. A high ADAR1 expression was a predictive factor of remnant liver recurrence (area under the curve = 0.72). Results showed that the ADAR1 expression level could be a clinically relevant predictive indicator of remnant liver recurrence. Patients with liver metastases who have a high ADAR1 expression requires adjuvant chemotherapy after hepatic metastasectomy. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0041-1132 63 7 2023 Efficient granulocyte collection method using high concentrations of medium molecular weight hydroxyethyl starch 1344 1353 EN Takumi Kondo Division of Transfusion, Okayama University Hospital Keiko Fujii Division of Clinical Laboratory, Okayama University Hospital Nobuharu Fujii Division of Transfusion, Okayama University Hospital Yuichi Sumii Division of Transfusion, Okayama University Hospital Tomohiro Urata Division of Transfusion, Okayama University Hospital Maiko Kimura Division of Transfusion, Okayama University Hospital Masayuki Matsuda Division of Transfusion, Okayama University Hospital Shuntaro Ikegawa Division of Transfusion, Okayama University Hospital Kana Washio Department of Pediatrics/Pediatric Hematology and Oncology, Okayama University Hospital Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Daisuke Ennishi Department of Hematology and Oncology, Okayama University Hospital Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital Ken‐ichi Matsuoka Department of Hematology and Oncology, Okayama University Hospital Fumio Otsuka Division of Clinical Laboratory, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Background: Granulocyte transfusion therapy is a rational therapeutic option for patients with prolonged, severe neutropenia. Although high molecular weight hydroxyethyl starch (hHES) facilitates the separation of red blood cells during granulocyte collection, renal dysfunction has been noted as a potential side effect. HES130/0.4 (Voluven®) is a medium molecular weight HES (mHES) with superior safety profiles compared to hHES. Although HES130/0.4 is reportedly effective in the collection of granulocytes, we lack studies comparing the efficiency of granulocyte collection using HES130/0.4 and hHES. Study Design and Methods: We retrospectively collected the data from 60 consecutive apheresis procedures performed on 40 healthy donors at the Okayama University Hospital between July 2013 and December 2021. All procedures were performed using the Spectra Optia system. Based on the HES130/0.4 concentration in the separation chamber, granulocyte collection methods using HES130/0.4 were classified into m0.46, m0.44, m0.37, and m0.8 groups. We used HES130/0.4 and hHES groups to compare the various sample collection methods. Results: The median granulocyte collection efficiency (CE) was approximately 24.0% and 28.1% in the m0.8 and hHES groups, respectively, which were significantly higher than those in the m0.46, m0.44, and m0.37 groups. One month following granulocyte collection with HES130/0.4, no significant changes were observed in serum creatinine levels compared to those before the donation. Conclusion: Therefore, we propose a granulocyte collection approach employing HES130/0.4, which is comparable to the use of hHES in terms of the granulocyte CE. A high concentration of HES130/0.4 in the separation chamber was considered crucial for granulocyte collection. No potential conflict of interest relevant to this article was reported.

Elsevier Ltd. Acta Medica Okayama 1341-321X 29 9 2023 Super acute-onset disseminated BCG infection: A case report 919 921 EN Ryosuke Takase Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takumi Fujimori Microbiology Division, Clinical Laboratory, Okayama University Hospital Yukika Yokoyama Microbiology Division, Clinical Laboratory, Okayama University Hospital Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kou Hasegawa 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 Intravesical Bacillus Calmette-Guérin (BCG) instillation is an established immunotherapy for superficial bladder cancer. Herein, we describe a case of disseminated BCG infection that developed immediately after the first BCG injection. A 76-year-old man diagnosed with non-invasive bladder cancer underwent intravesical BCG instillation; he developed high fever and systemic arthralgia later that night. General examination did not reveal any infectious sources, and a combination therapy of isoniazid, rifabutin, and ethambutol was initiated after collecting his blood, urine, bone marrow, and liver biopsy samples for mycobacterial cultures. Three weeks later, Mycobacterium bovis was detected in the urine and bone marrow samples, and pathological investigation of liver biopsy revealed multiple small epithelial granulomas with focal multinucleated giant cells, leading to a diagnosis of disseminated BCG infection. The patient recovered after long-term antimycobacterial therapy without remarkable sequelae. Most cases of disseminated BCG infection occur after several doses of BCG injections, and its onset reportedly varies among cases, ranging from a few days to several months. The present case was notable as disease onset was observed only a few hours after the first BCG injection. Although rare, development of disseminated BCG infection should be considered as a differential diagnosis in patients at any time after intravesical BCG instillation therapy. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1477-8939 52 2023 Shigellosis in Southeast Asia: A systematic review and meta-analysis 102554 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 Debmalya Mitra Collaborative Research Centre of Okayama University for Infectious Diseases in India at ICMR-NICED 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 Background: Southeast Asia is attractive for tourism. Unfortunately, travelers to this region are at risk of becoming infected with Shigella. We conducted a meta-analysis to provide updates on Shigella prevalence in Southeast Asia, along with their serogroups and serotypes. Methods: We conducted a systematic search using PubMed, EMBASE, and Web of Science for peer-reviewed studies from 2000 to November 2022. We selected studies that detected Shigella in stools by culture or polymerase chain reaction (PCR). Two reviewers extracted the data using a standardized form and performed quality assessments using the Joanna Briggs Institute checklist. The random effects model was used to estimate the pooled prevalence of Shigella. Results: During our search, we identified 4376 studies. 29 studies (from six Southeast Asian countries) were included in the systematic review, 21 each in the meta-analysis of the prevalence of Shigella (Sample size: 109545) and the prevalence of Shigella serogroups. The pooled prevalence of Shigella was 4% (95% CI: 4–5%) among diarrhea cases. Shigella sonnei was the most abundant serogroup in Thailand (74%) and Vietnam (57%), whereas Shigella flexneri was dominant in Indonesia (72%) and Cambodia (71%). Shigella dysenteriae and Shigella boydii were uncommon (pooled prevalence of 1% each). The pooled prevalence of Shigella was 5% (95% CI: 4–6%) in children aged <5 years. The pooled prevalence showed a decreasing trend comparing data collected between 2000–2013 (5%; 95% CI: 4–6%) and between 2014–2022 (3%; 95% CI: 2–4%). Shigella prevalence was 6% in studies that included participants with mixed pathogens versus 3% in those without. Shigella flexneri serotype 2a was the most frequently isolated (33%), followed by 3a (21%), 1b (10%), 2b (3%), and 6 (3%). Conclusions: This study provides compelling evidence for the development of effective Shigella vaccines for residents of endemic regions and travellers to these areas. No potential conflict of interest relevant to this article was reported.

nature portfolio Acta Medica Okayama 2045-2322 12 1 2022 Early-stage antibody kinetics after the third dose of BNT162b2 mRNA COVID-19 vaccination measured by a point-of-care fingertip whole blood testing 20628 EN Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Furukawa Clinical Laboratory, Okayama University Hospital Naruhiko Sunada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasue Sakurada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kou Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroko Ogawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kouhei Ageta Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naomi Matsumoto Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rumi Matsuo Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoka Kadowaki Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihito Higashikage Clinical Laboratory, Okayama University Hospital Takao Hikita Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Departments of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Yokokura Yokokura Hospital Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Nakayama Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University Amid the Coronavirus Disease 2019 pandemic, we aimed to demonstrate the accuracy of the fingertip whole blood sampling test (FWT) in measuring the antibody titer and uncovering its dynamics shortly after booster vaccination. Mokobio SARS-CoV-2 IgM & IgG Quantum Dot immunoassay (Mokobio Biotechnology R&D Center Inc., MD, USA) was used as a point-of-care FWT in 226 health care workers (HCWs) who had received two doses of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) at least 8 months prior. Each participant tested their antibody titers before and after the third-dose booster up to 14-days. The effect of the booster was observed as early as the fourth day after vaccination, which exceeded the detection limit (>30,000 U/mL) by 2.3% on the fifth day, 12.2% on the sixth day, and 22.5% after the seventh day. Significant positive correlations were observed between the pre- and post-vaccination (the seventh and eighth days) antibody titers (correlation coefficient, 0.405; p<0.001). FWT is useful for examining antibody titers as a point-of-care test. Rapid response of antibody titer started as early as the fourth day post-vaccination, while the presence of weak responders to BNT162b2 vaccine was indicated. No potential conflict of interest relevant to this article was reported.

nature portfolio Acta Medica Okayama 2045-2322 13 1 2023 Identification of genetic loci associated with renal dysfunction after lung transplantation using an ethnic-specific single-nucleotide polymorphism array 8912 EN Yasuaki Tomioka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruchika Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Toshio Shiotani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Otani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikio Okazaki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaomi Yamane Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Renal dysfunction is a long-term complication associated with an increased mortality after lung transplantation (LT). We investigated the association of single-nucleotide polymorphisms (SNPs) with the development of renal dysfunction after LT using a Japanese-specific SNP array. First, eligible samples of 34 LT recipients were genotyped using the SNP array and divided into two groups, according to the presence of homozygous and heterozygous combinations of mutant alleles of the 162 renal-related SNPs. To identify candidate SNPs, the renal function tests were compared between the two groups for each SNP. Next, we investigated the association between the candidate SNPs and the time course of changes of the estimated glomerular filtration rate (eGFR) in the 99 recipients until 10 years after the LT. Delta eGFR was defined as the difference between the postoperative and preoperative eGFR values. Eight SNPs were identified as the candidate SNPs in the 34 recipients. Validation analysis of these 8 candidate SNPs in all the 99 recipients showed that three SNPs, namely, rs10277115, rs4690095, and rs792064, were associated with significant changes of the Delta eGFR. Pre-transplant identification of high-risk patients for the development of renal dysfunction after LT based on the presence of these SNPs might contribute to providing personalized medicine. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1059-1311 107 2023 Comprehensive study of metabolic changes induced by a ketogenic diet therapy using GC/MS- and LC/MS-based metabolomics 52 59 EN Mari Akiyama Department of Child Neurology, Okayama University Hospital Tomoyuki Akiyama Department of Paediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Saigusa Tohoku Medical Megabank Organization, Tohoku University Eiji Hishinuma Tohoku Medical Megabank Organization, Tohoku University Naomi Matsukawa Tohoku Medical Megabank Organization, Tohoku University Takashi Shibata Department of Child Neurology, Okayama University Hospital Hiroki Tsuchiya Department of Child Neurology, Okayama University Hospital Atsushi Mori Department of Neurology, Shiga Medical Centre for Children Yuji Fujii Department of Paediatrics, Hiroshima City Funairi Citizens Hospital Yukiko Mogami Department of Paediatric Neurology, Osaka Women's and Children's Hospital Chiho Tokorodani Department of Paediatrics, Kochi Health Sciences Centre Kozue Kuwahara Department of Paediatrics, Ehime Prefectural Central Hospital, Yurika Numata-Uematsu Department of Paediatrics, Tohoku University School of Medicine Kenji Inoue Department of Neurology, Shiga Medical Centre for Children Katsuhiro Kobayashi Department of Paediatrics (Child Neurology), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objective: The ketogenic diet (KD), a high-fat and low-carbohydrate diet, is effective for a subset of patients with drug-resistant epilepsy, although the mechanisms of the KD have not been fully elucidated. The aims of this observational study were to investigate comprehensive short-term metabolic changes induced by the KD and to explore candidate metabolites or pathways for potential new therapeutic targets. Methods: Subjects included patients with intractable epilepsy who had undergone the KD therapy (the medium-chain triglyceride [MCT] KD or the modified Atkins diet using MCT oil). Plasma and urine samples were obtained before and at 2–4 weeks after initiation of the KD. Targeted metabolome analyses of these samples were performed using gas chromatography-tandem mass spectrometry (GC/MS/MS) and liquid chromatography-tandem mass spectrometry (LC/MS/MS). Results: Samples from 10 and 11 patients were analysed using GC/MS/MS and LC/MS/MS, respectively. The KD increased ketone bodies, various fatty acids, lipids, and their conjugates. In addition, levels of metabolites located upstream of acetyl-CoA and propionyl-CoA, including catabolites of branched-chain amino acids and structural analogues of γ-aminobutyric acid and lactic acid, were elevated. Conclusions: The metabolites that were significantly changed after the initiation of the KD and related metabolites may be candidates for further studies for neuronal actions to develop new anti-seizure medications. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 3 2023 Endocrinological Changes after Anamorelin Administration in Patients with Gastrointestinal Cancer 235 241 EN Sakiko Kuraoka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Satomi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsuhiro Yamazaki Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenta Hamada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiyasu Kono Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromitsu Kanzaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hironari Kato Department of Gastroenterology and Hepatology, 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 Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65488 Changes in hormone levels in patients with cancer cachexia after anamorelin administration have not been fully investigated. This study aimed to determine how anamorelin affects the endocrine system in patients with gastrointestinal cancer and cachexia. We prospectively enrolled 13 patients and comprehensively investigated their body weight and levels of serum albumin, hemoglobin A1c (HbA1c), and hormones before (week 0) and 3 and 12 weeks after anamorelin administration. The variables were evaluated at week 3 in 9 patients and at week 12 in 5 patients. At week 3, anamorelin administration resulted in body weight gain and increased the levels of growth hormone and HbA1c, as well as insulin-like growth factor-1 standard deviation scores (IGF-1 SD scores). At the same time, negative correlations were observed between ΔIGF-1 SD score and Δthyroidstimulating hormone (TSH) and between ΔIGF-1 SD score and Δfree testosterone. ΔBody weight and ΔIGF-1 SD score correlated positively at week 12. These results suggest that TSH and free testosterone levels can be affected 3 weeks after anamorelin administration; however, those variables tend to return to a state of equilibrium, and anabolic effects of anamorelin appear in long-term (≥ 12 weeks) users. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 1664-302X 14 2023 Etiology of recurrent cystitis in postmenopausal women based on vaginal microbiota and the role of Lactobacillus vaginal suppository 1187479 EN Takanori Sekito Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Koichiro Wada Department of Urology, Shimane University Faculty of Medicine Ayano Ishii Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Takehiro Iwata Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Takehiro Matsubara Okayama University Hospital Biobank, Okayama University Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Background: The vaginal microbiota can be altered by uropathogenic bacteria associated with recurrent cystitis (RC), and the vaginal administration of Lactobacillus have suggested certain effects to prevent RC. The relationship between vaginal microbiota and the development of RC has not been elucidated. We aimed to clarify the etiology of RC from vaginal microbiota and importance of vaginal Lactobacillus. Methods: Vaginal samples obtained from 39 postmenopausal women were classified into four groups: healthy controls; uncomplicated cystitis; RC; and prevention (prevented RC by Lactobacillus crispatus-containing vaginal suppositories). Principal coordinate analysis and beta-diversity analysis was used to assess 16S rRNA gene sequencing data from the vaginal microbiome. Results: Cluster analysis divided the vaginal bacterial communities among 129 vaginal samples into three clusters (A, B, and C). Fourteen of 14 (100%) samples from the RC group and 51 of 53 (96%) samples from the prevention group were in clusters B and C, while 29 of 38 (76%) samples from the healthy group and 14 of 24 (58%) samples from the uncomplicated cystitis group were in cluster A. The principal coordinate analysis showed that plots in the uncomplicated cystitis group were similar to the healthy group, indicating a large separation between the RC group and the uncomplicated cystitis group. On beta-diversity analysis, there were significant differences between the healthy group and the uncomplicated cystitis group (p = 0.045), and between the RC group and the uncomplicated cystitis group or the healthy group (p = 0.001, p = 0.001, respectively). There were no significant differences between the RC group and the prevention group (p = 0.446). The top six taxa were as follows: Prevotella, Lactobacillus, Streptococcus, Enterobacteriaceae, Anaerococcus, and Bifidobacterium. Among patients with RC, Lactobacillus was undetectable before administration of suppositories, while the median relative abundance of Lactobacillus was 19% during administration of suppositories (p = 0.0211), reducing the average cystitis episodes per year (6.3 vs. 2.4, p = 0.0015). Conclusion: The vaginal microbiota of postmenopausal women with RC is differed from healthy controls and uncomplicated cystitis in terms of lack of Lactobacillus and relatively dominant of Enterobacteriaceae. Vaginal administration of Lactobacillus-containing suppositories can prevent RC by stabilizing vaginal dysbiosis and causing a loss of pathogenic bacteria virulence. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 18 3 2023 Consistently low levels of histidine-rich glycoprotein as a new prognostic biomarker for sepsis: A multicenter prospective observational study e0283426 EN Naoya Kawanoue Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosuke Kuroda Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroko Yasuda Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiko Oiwa Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Suzuki Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidenori Wake Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Hosoi Data Science Division, Center for Innovative Clinical Medicine, Okayama University Hospital Masahiro Nishibori Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Few sepsis biomarkers accurately predict severity and mortality. Previously, we had reported that first-day histidine-rich glycoprotein (HRG) levels were significantly lower in patients with sepsis and were associated with mortality. Since the time trends of HRG are unknown, this study focused on the time course of HRG in patients with sepsis and evaluated the differences between survivors and non-survivors. Methods A multicenter prospective observational study was conducted involving 200 patients with sepsis in 16 Japanese hospitals. Blood samples were collected on days 1, 3, 5, and 7, and 28-day mortality was used for survival analysis. Plasma HRG levels were determined using a modified quantitative sandwich enzyme-linked immunosorbent assay. Results First-day HRG levels in non-survivors were significantly lower than those in survivors (mean, 15.7 [95% confidence interval (CI), 13.4-18.1] vs 20.7 [19.5-21.9] mu g/mL; P = 0.006). Although there was no time x survivors/non-survivors interaction in the time courses of HRG (P = 0.34), the main effect of generalized linear mixed models was significant (P < 0.001). In a univariate Cox proportional hazards model with each variable as a time-dependent covariate, higher HRG levels were significantly associated with a lower risk of mortality (hazard ratio, 0.85 [95% CI, 0.78-0.92]; P < 0.001). Furthermore, presepsin levels (P = 0.02) and Sequential Organ Function Assessment scores (P < 0.001) were significantly associated with mortality. Harrell's C-index values for the 28-day mortality effect of HRG, presepsin, procalcitonin, and C-reactive protein were 0.72, 0.70, 0.63, and 0.59, respectively. Conclusions HRG levels in non-survivors were consistently lower than those in survivors during the first seven days of sepsis. Repeatedly measured HRG levels were significantly associated with mortality. Furthermore, the predictive power of HRG for mortality may be superior to that of other singular biomarkers, including presepsin, procalcitonin, and C-reactive protein. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2196-4092 10 1 2023 Absence of Cretaceous hairpin in the apparent polar wander path of southwest Japan: consistency in paleomagnetic pole positions 21 EN Koji Uno Department of Earth Sciences, Okayama University Honoka Ohara Department of Earth Sciences, Okayama University Kuniyuki Furukawa Faculty of Business Administration, Aichi University Tatsuo Kanamaru Department of Earth and Environmental Sciences, Nihon University To test the hypothesis that a Cretaceous hairpin turn is absent in the apparent polar wander path (APWP) of the inner arc of southwestern Japanese island (southwest Japan), we refined a mid-Cretaceous (100 Ma) paleomagnetic pole from southwest Japan. Red mudstone samples from the 100 Ma Hayama Formation were collected for paleomagnetic analysis from eight sites in the Hayama area in the central part of southwest Japan. A high-temperature remanent magnetization component carried by hematite was isolated from these sites and was found to be of primary mid-Cretaceous origin. The primary nature of the magnetization is supported by the detrital character of the magnetic carrier. The primary directions provided a paleomagnetic pole (35.0 degrees N, 209.6 degrees E, A(95) = 6.1 degrees, N = 8), which represented southwest Japan at 100 Ma. This pole falls into a cluster of Cretaceous poles in southwest Japan. An APWP for southwest Japan between 110 and 70 Ma was updated to ascertain the stationarity of the pole positions for this region. Therefore, it is unlikely that the APWP for southwest Japan experienced a hairpin turn during the Cretaceous. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 1664-1078 14 2023 Home literacy environment and early reading skills in Japanese Hiragana and Kanji during the transition from kindergarten to primary school 1052216 EN Takayuki Tanji Okayama University Tomohiro Inoue The Chinese University of Hong Kong We examined the reciprocal associations between home literacy environment (HLE) and children's early reading skills in syllabic Hiragana and morphographic Kanji in a sample of Japanese parent-child dyads. Eighty-three children were followed from kindergarten to Grade 3 and tested on Hiragana reading accuracy in kindergarten, Hiragana word reading fluency in kindergarten and Grade 1, and Kanji reading accuracy in Grade 1 to Grade 3. Their parents answered a questionnaire about HLE [parent teaching (PT) in Hiragana and Kanji, shared book reading (SBR), and access to literacy resources (ALR)], parents' needs for early literacy support by teachers, parents' expectations for children's reading skills, parents' worry about children's homework, and mother's education level. Results showed first that ALR, but not PT and SBR, was associated with reading skills in Hiragana and Kanji. Second, whereas Hiragana reading in kindergarten was not associated with PT in Hiragana in kindergarten, it negatively predicted PT in Hiragana in Grade 1. However, Kanji reading accuracy was not associated with PT in Kanji across Grades 1 to 3. Third, parents' worry was negatively associated with children's reading performance across Grades 1 to 3 but positively associated with PT in Hiragana and Kanji. Finally, while parents' expectations were positively associated with children's reading performance across Grades 1 to 3, they were negatively associated with PT in Hiragana and Kanji in Grades 1 and 2. These results suggest that Japanese parents may be sensitive to both their children's reading performance and social expectations for school achievement and adjust their involvement accordingly during the transition period from kindergarten to early primary grades. ALR may be associated with early reading development in both Hiragana and Kanji. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 134 2 2022 バイオバンクと残余検体使用の考え方 119 122 EN Hideki Yamamoto Department of Clinical Genomic Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akira Hirasawa Department of Clinical Genomic Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2306-7381 10 3 2023 Monitoring the Milk Composition, Milk Microbiota, and Blood Metabolites of Jersey Cows throughout a Lactation Period 226 EN Peter Kiiru Gathinji Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University Zabiallah Yousofi Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University Karin Akada Animal Products Research Group, Institute of Livestock and Grassland Science, National Agriculture and Research Organization Ajmal Wali Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University Naoki Nishino Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University This study aimed to determine how milk composition, milk microbiota, and blood metabolites may change during the lactation period in Jersey cows. Milk and jugular blood samples were collected from eight healthy cows every other month from the beginning to the end of their lactation period. Samples of airborne dust were also collected to determine whether the cowshed microbiota could affect milk microbiota. Milk yield peaked in the first two months and gradually decreased as the lactation period progressed. Milk fat, protein, and solids-not-fat contents were low in the first month, and then increased during the middle and late lactation periods. In the first month, plasma non-esterified fatty acids (NEFA), haptoglobin (Hp), and aspartate transaminase (AST) levels were elevated, and high abundances of Burkholderiaceae and Oxalobacteraceae were observed in milk and airborne dust microbiota. The finding that contamination of the environmental microbiota in milk was coupled with elevated plasma NEFA, Hp, and AST levels indicated that impaired metabolic function during the early lactation period may increase the invasion of opportunistic bacteria. This study can affirm the importance of feeding and cowshed management and should provide a helpful addition to improving Jersey cow farming. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 2 2023 Evaluating the Coping Behavior of Children with Psychosomatic Disorders under Frustrating Situations Simulated Using the Rosenzweig Picture-Frustration Study 185 192 EN Akiko Sugihara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayumi Okada Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Makiko Horiuchi Clinical Psychology section, Department of Medical Support, Okayama University Hospital Department of Medical Support Mayumi Yabe Clinical Psychology section, Department of Medical Support, Okayama University Hospital Department of Medical Support Yoshie Shigeyasu Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chikako Fujii Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chie Tanaka Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65148 Psychosomatic disorders are influenced by psychosocial factors such as interpersonal relationships. Coping behaviors, especially in frustrating situations, reflect a patient’s ability to cope with stress, and it is important to assess these behaviors for the treatment of psychosomatic diseases. This study aimed to clarify the interpersonal relationships and coping behaviors of pediatric patients with psychosomatic diseases during frustrating situations simulated using the Rosenzweig Picture-Frustration study. This retrospective study included 126 patients (41 male, 85 female) with an average age of 12.9 (6-16) years who were consulted at the Department of Pediatric Psychosomatic Medicine at Okayama University Hospital from 2013 to 2018 and underwent the P-F study. Each score was compared with a standardization sample. The mean group conformity rating did not differ significantly between the participants and healthy children. Compared with healthy children, those with psychosomatic diseases were less likely to explain their perspective. The children with psychosomatic disorders responded to frustrating situations in a sensible and age-appropriate manner. However, they were less likely to respond by explaining their perspective to protect themselves. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 24 6 2023 Stress-Inducible SCAND Factors Suppress the Stress Response and Are Biomarkers for Enhanced Prognosis in Cancers 5168 EN Mona Sheta Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kunihiro Yoshida Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hideka Kanemoto Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Stuart K. Calderwood Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School Takanori Eguchi Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The cell stress response is an essential system present in every cell for responding and adapting to environmental stimulations. A major program for stress response is the heat shock factor (HSF)-heat shock protein (HSP) system that maintains proteostasis in cells and promotes cancer progression. However, less is known about how the cell stress response is regulated by alternative transcription factors. Here, we show that the SCAN domain (SCAND)-containing transcription factors (SCAN-TFs) are involved in repressing the stress response in cancer. SCAND1 and SCAND2 are SCAND-only proteins that can hetero-oligomerize with SCAN-zinc finger transcription factors, such as MZF1(ZSCAN6), for accessing DNA and transcriptionally co-repressing target genes. We found that heat stress induced the expression of SCAND1, SCAND2, and MZF1 bound to HSP90 gene promoter regions in prostate cancer cells. Moreover, heat stress switched the transcript variants' expression from long noncoding RNA (lncRNA-SCAND2P) to protein-coding mRNA of SCAND2, potentially by regulating alternative splicing. High expression of HSP90AA1 correlated with poorer prognoses in several cancer types, although SCAND1 and MZF1 blocked the heat shock responsiveness of HSP90AA1 in prostate cancer cells. Consistent with this, gene expression of SCAND2, SCAND1, and MZF1 was negatively correlated with HSP90 gene expression in prostate adenocarcinoma. By searching databases of patient-derived tumor samples, we found that MZF1 and SCAND2 RNA were more highly expressed in normal tissues than in tumor tissues in several cancer types. Of note, high RNA expression of SCAND2, SCAND1, and MZF1 correlated with enhanced prognoses of pancreatic cancer and head and neck cancers. Additionally, high expression of SCAND2 RNA was correlated with better prognoses of lung adenocarcinoma and sarcoma. These data suggest that the stress-inducible SCAN-TFs can function as a feedback system, suppressing excessive stress response and inhibiting cancers. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2079-6382 12 3 2023 The Genotypic and Phenotypic Characteristics Contributing to Flomoxef Sensitivity in Clinical Isolates of ESBL-Producing E. coli Strains from Urinary Tract Infections 522 EN Kazuma Sakaeda Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuya Sadahira Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Maruyama Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takehiro Iwata Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masami Watanabe Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koichiro Wada Koichiro Wada Department of Urology, School of Medicine, Shimane University Motoo Araki Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University We carried out a molecular biological analysis of extended-spectrum beta-lactamase (ESBL)-producing E. coli strains and their sensitivity to flomoxef (FMOX). Sequence type (ST) analysis by multilocus sequence typing (MLST) and classification of ESBL genotypes by multiplex PCR were performed on ESBL-producing E. coli strains isolated from urine samples collected from patients treated at our institution between 2008 and 2018. These sequences were compared with results for antimicrobial drug susceptibility determined using a micro-liquid dilution method. We also analyzed cases treated with FMOX at our institution to examine its clinical efficacy. Of the 911 E. coli strains identified, 158 (17.3%) were ESBL-producing. Of these, 67.7% (107/158) were strain ST-131 in ST analysis. Nearly all (154/158; 97.5%) were CTX-M genotypes, with M-14 and M-27 predominating. The isolated strains were sensitive to FMOX in drug susceptibility tests. Among the patient samples, 33 cases received FMOX, and of these, 5 had ESBL-producing E. coli. Among these five cases, three received FMOX for surgical prophylaxis as urinary carriers of ESBL-producing E. coli, and postoperative infections were prevented in all three patients. The other two patients received FMOX treatment for urinary tract infections. FMOX treatment was successful for one, and the other was switched to carbapenem. Our results suggest that FMOX has efficacy for perioperative prophylactic administration in urologic surgery involving carriers of ESBL-producing bacteria and for therapeutic administration for urinary tract infections. Use of FMOX avoids over-reliance on carbapenems or beta-lactamase inhibitors and thus is an effective antimicrobial countermeasure. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1932-7447 127 5 2023 Uniform Formation of a Characteristic Nanocomposite Structure of Biogenous Iron Oxide for High Rate Performance as the Anode of Lithium-Ion Batteries 2223 2230 EN Masakuni Takahashi Graduate School of Natural Science and Technology, Okayama University Ryo Sakuma Graduate School of Natural Science and Technology, Okayama University Hideki Hashimoto Graduate School of Natural Science and Technology, Okayama University Tatsuo Fujii Graduate School of Natural Science and Technology, Okayama University Jun Takada Graduate School of Natural Science and Technology, Okayama University Recently, Fe2O3 has been considered as an alternative anode material for lithium-ion batteries (LIBs) owing to its high theoretical capacity (approximately 1000 mA h g-1), low cost, and nontoxicity. However, its rate performance remains poor relative to that of the conventional graphite anode. In this study, Fe2O3-based anodes were prepared through the annealing of biogenous Fe2O3 (L-BIOX) samples produced by an aquatic Fe-oxidizing bacterium. The effect of the annealing temperature on the performance of the synthesized Fe2O3-based material as the anode of an LIB was investigated. Electrochemical measurements revealed that the annealed L-BIOX samples at 300-700 degrees C exhibited higher rate performances than the unannealed material. Particularly, the sample annealed at 700 degrees C exhibited the highest capacity among the synthesized materials and showed a higher performance than the previously reported Fe2O3-based anodes. It exhibited a capacity of 923 mA h g-1 even at a high current density of 2 A g-1. After annealing at 700 degrees C and discharging, the synthesized biogenous material had a uniform nanocomposite structure composed of alpha-Fe2O3 nanoparticles dispersed in an amorphous matrix of Li-Si-P oxide. To form this uniform nanostructure, the solid-state diffusion resistance of the Li+ ions in the active material was reduced, which consequently improved the rate performance of the electrode. Therefore, this study provides substantial insights into the development and improvement of the performance of novel Fe2O3-based nanomaterials as the anode of LIBs. No potential conflict of interest relevant to this article was reported.

Spandidos Publications Acta Medica Okayama 2049-9450 18 2 2022 Bladder tuberculosis with ureteral strictures after bacillus Calmette‑Guérin therapy for urinary bladder cancer: A case report 7 EN Yusuke Tominaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Fujii Department of Allergy and Respiratory Medicine, Okayama University Hospital Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Iwata Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Edamura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Allergy and Respiratory Medicine, Okayama University Hospital Koichiro Wada Department of Urology, Shimane University Faculty of Medicine Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Intravesical immunotherapy using bacillus Calmette‑Guérin (BCG) is recommended for patients with intermediate‑ to high‑risk non‑muscle invasive bladder cancer. Bladder tuberculosis (TB) is a rare complication of BCG therapy. The present study describes the case of a 73‑year‑old man who underwent intravesical BCG therapy for urothelial carcinoma in situ of the bladder. Red patches around the resection scar were first detected 1 year and 5 months after BCG treatment; these findings gradually spread to encompass more of the bladder wall. Transurethral biopsy revealed a benign lesion, but the patient developed bilateral hydronephrosis and mild voiding dysfunction. The patient was eventually diagnosed with bladder TB by mycobacterial urine culture and TB‑specific polymerase chain reaction (PCR). The patient was given multidrug therapy (isoniazid, rifampicin and ethambutol) and their bladder TB was completely cured; however, their voiding dysfunction and bilateral hydronephrosis did not fully improve. Bladder TB can occur long after intravesical BCG administration and cystoscopy findings consistent with inflammation can be the key to suspecting this condition. Acid‑fast examination and PCR testing of a urine sample are necessary for early diagnosis. No potential conflict of interest relevant to this article was reported.

岡山大学全学教育・学生支援機構 Acta Medica Okayama 2432-9665 7 2023 英語を通じた内容学習の試み：The Intersection of Arts, Humanities, and Science を活用した授業紹介 1 15 EN Azumi Yoshida Masayuki Teranishi 10.18926/64993 In this paper we review our class activities using The Intersection of Arts, Humanities, and Science (2020), which was coauthored by the members of The Japan Association of International Liberal Arts with the aim of integrating content and language learning according to the concept of CLIL (Content and Language Integrated Learning). The book includes not only topics to stimulate university students'intellectual curiosity but also various activities through which students can read, think, and express themselves in English. Based on our reflective review of class activities and student samples, we discuss possible pedagogical effects and further improvements of CLIL. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1752-1947 17 1 2023 Thrombocytopenia, anasarca, and renal insufficiency as severe and rare complications of Hodgkin lymphoma: a case report 61 EN Tatsuya Kikuchi Department of Gastroenterology, Okayama University Hospital Yoshinori Tanaka Department of Hematology, Hiroshima City Hiroshima Citizens Hospital Kouichi Ichimura Department of Pathology, Hiroshima City Hiroshima Citizens Hospital Hiroyuki Okada Department of Gastroenterology, Okayama University Hospital Ryoichi Okamoto Department of Internal Medicine, Hiroshima City Hiroshima Citizens Hospital BackgroundPatients with Hodgkin lymphoma exhibit various clinical presentations. Needle biopsy of the lymph nodes is a minimally invasive procedure and a useful diagnostic method for malignant lymphomas. However, at times it is difficult to differentiate malignant lymphomas from reactive lymph node changes using a small amount of biopsy material.Case presentationA 77-year-old Japanese man was referred to the emergency department of our hospital owing to high fever and disturbance of consciousness. We diagnosed sepsis due to an acute biliary tract infection because he presented with Charcot's triad-fever, jaundice, and right-sided abdominal pain. However, he did not respond well to antimicrobial therapy and his high fever persisted. Considering the swelling of the right cervical, mediastinal, and intraperitoneal lymph nodes and splenomegaly detected on computed tomography, a differential diagnosis of malignant lymphoma was needed. Hence, we performed a needle biopsy of the right cervical lymph node; however, the amount of sample obtained was insufficient in establishing a definitive diagnosis of malignant lymphoma. Furthermore, during hospitalization, the patient developed thrombocytopenia, anasarca, and renal insufficiency. These symptoms seemed to be the typical signs of the thrombocytopenia, anasarca, fever, reticulin fibrosis or renal insufficiency, and organomegaly syndrome. Next, an external incisional mass biopsy of the right cervical lymph node was performed, which helped identify Hodgkin and Reed-Sternberg cells. Collectively, we established a definitive diagnosis of Hodgkin lymphoma with lymphoma-associated hemophagocytic syndrome.ConclusionsThis case highlights the importance of performing an external incisional mass biopsy of the lymph nodes for the early diagnosis and treatment, if malignant lymphoma is strongly suspected. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 24 3 2023 Microcalcification and Tc-99m-Pyrophosphate Uptake without Increased Bone Metabolism in Cardiac Tissue from Patients with Transthyretin Cardiac Amyloidosis 1921 EN Atsushi Mori Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yukihiro Saito Department of Cardiovascular Medicine, Okayama University Hospital Kazufumi Nakamura Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshihiro Iida Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Akagi Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masashi Yoshida Department of Chronic Kidney Disease and Cardiovascular Disease, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Makiko Taniyama Department of General Medicine, Tamano Division, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Miyoshi 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 Transthyretin cardiac amyloidosis (ATTR-CA) is characterized by high Tc-99m-labeled bone tracer uptake in the heart. However, the mechanism of bone tracer uptake into the heart remains controversial. Since bone tracer uptake into metastatic bone tumors is thought to be associated with increased bone metabolism, we examined Tc-99m-pyrophosphate (PYP) scintigraphy findings, endomyocardial biopsy (EMB) tissue findings, and the expression of bone metabolism-related genes in the EMB tissues in patients with ATTR-CA, amyloid light-chain cardiac amyloidosis (AL-CA), and noncardiac amyloidosis (non-CA) in this study. The uptake of Tc-99m-PYP in the heart was significantly higher in the ATTR-CA patients than in the AL-CA and non-CA patients. A higher percentage of ATTR-CA EMB tissue showed von Kossa-positive microparticles: ATTR-CA, 62%; AL-CA, 33%; and non-CA, 0%. Calcified microparticles were identified using transmission electron microscopy. However, none of the osteogenic marker genes, osteoclastic marker genes, or phosphate/pyrophosphate-related genes were upregulated in the EMB samples from ATTR-CA patients compared to those from AL-CA and non-CA patients. These results suggest that active calcification-promoting mechanisms are not involved in the microcalcification observed in the heart in ATTR-CA. The mechanisms explaining bone tracer uptake in the heart, which is stronger than that in the ribs, require further investigation. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1472-6920 23 1 2023 Eleven years of data on the Jefferson Scale of Empathy - medical student version: Japanese norm data and tentative cutoff scores 81 EN Hitomi U. Kataoka Center for Diversity and Inclusion, Okayama University Hospital Akiko Tokinobu Center for Diversity and Inclusion, Okayama University Hospital Chikako Fujii Center for Diversity and Inclusion, Okayama University Hospital Mayu Watanabe Division of Kidney, Diabetes and Endocrine Diseases, Okayama University Hospital Mikako Obika Department of General Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background More and more studies investigate medical students' empathy using the Jefferson Scale of Empathy (JSE). However, no norm data or cutoff scores of the JSE for Japanese medical students are available. This study therefore explored Japanese norm data and tentative cutoff scores for the Japanese translation of the JSE-medical student version (JSE-S) using 11 years of data obtained from matriculants from a medical school in Japan. Methods Participants were 1,216 students (836 men and 380 women) who matriculated at a medical school in Japan from 2011 to 2021. The JSE-S questionnaire was administered to participants prior to the start of the program. Data were summarized using descriptive statistics and statistical tests were performed to show the norm data and tentative cutoff scores for male and female students separately. Results The score distributions of the JSE-S were moderately skewed and leptokurtic for the entire sample, with indices -0.75 and 4.78, respectively. The mean score (standard deviation) for all participants was 110.8 (11.8). Women had a significantly higher mean score (112.6) than men (110.0; p < 0.01). The effect size estimate of gender difference was 0.22, indicating a small effect size. The low and high cutoff scores for men were <= 91 and >= 126, respectively, and the corresponding scores for women were <= 97 and >= 128, respectively. Conclusions This study provides JSE-S norm data and tentative cutoff scores for Japanese medical school matriculants, which would be helpful in identifying those who may need further training to enhance their empathy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 Development, Disappearance, and Clinical Course of Melanosis Coli: Sex Differences in the Progression of Severity 57 64 EN Ryo Katsumata Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center Noriaki Manabe Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical Center Yasumasa Monobe Pathology, Kawasaki Medical School General Medical Center Maki Ayaki Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical Center Mitsuhiko Suehiro Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center Minoru Fujita Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical Center Tomoari Kamada Health Care Medicine, Kawasaki Medical School General Medical Center Hirofumi Kawamoto Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center Ken Haruma Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center Original Article 10.18926/AMO/64362 Melanosis coli (MC) is an acquired colorectal disorder visualized as colonic mucosa pigmentation. Disease severity is confirmed based on MC depth, shape, and coloration, although the clinical course is not fully understood. This study sought to clarify characteristics of MC development and disappearance and to investigate its clinical course and severity. Contributors to MC grade progression were explored. This study reviewed MC cases discovered via colonoscopy at a single institution over a 10-year period. Of all 216 MC cases, 17 developing and 10 disappearing cases were detected. Anthranoid laxative use was a key factor: 29.4% of the developing cases had used such agents before the initial MC diagnosis, whereas 40% of disappearing cases had discontinued anthranoids prior to detection of MC disappearance. Among 70 grade I cases, progression to grade II occurred in 16 cases during a mean follow-up of 3.67±2.1 years (rate of progression=22.8%). Males more commonly showed progressive than stable grade I cases, and the probability of progression was higher for male than for female cases. An association between anthranoid administration and MC presence was presumed, and grade I MC was found to progress in severity over 5 years. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 Prevalence of Inducible Macrolide, Lincosamide, and Streptogramin B (inducible MLSB) Resistance in Clindamycin-Susceptible Staphylococcus aureus at Okayama University Hospital 1 9 EN Lutfun Nahar Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Nada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Kazuyoshi Gotoh Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Osamu Matsushita Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/64355 Inducible resistance to the macrolide, lincosamide, and streptogramin B (iMLSB) antibiotic family is a latent mechanism for antimicrobial resistance in Staphylococcus aureus. We here investigated the frequency and genotypic profiles of iMLSB resistance in clindamycin (CLDM)-susceptible S. aureus isolated in Okayama University Hospital from June 2020 to June 2021. We phenotypically screened the iMLSB resistance via D-zone test and performed PCR testing for the erythromycin ribosomal methylase (erm) genes: ermA and ermC. Among 432 CLDM-susceptible S. aureus isolates, 138 (31.9%) exhibited an iMLSB-resistance phenotype, with methicillinresistant S. aureus isolates (MRSA; 61 isolates: 58.6%) exhibiting higher positivity than methicillin-sensitive S. aureus isolates (MSSA; 77 isolates: 23.5%) (p<0.001). Male patients had a higher frequency of iMLSB resistance than females (OR [95%CI]: 1.8 [1.2-2.8]; p=0.007). Genotypically, ermA predominated in both MSSA (70.1%) and MRSA (86.9%) compared to ermC (14.3% in MSSA and 11.5% in MRSA). A single strain of MRSA possessed both ermA and ermC, while 12 (15.6%) MSSA isolates were negative for both ermA and ermC, suggesting the presence of other genetic mechanisms. Collectively, these results show that approximately 33% of CLDM-susceptible S. aureus isolates at our university hospital exhibited iMLSB resistance, predominantly caused by ermA in both MSSA and MRSA. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9059 11 1 2023 Longitudinal Measurement of Histidine-Rich Glycoprotein Levels in Bronchopulmonary Dysplasia: A Pilot Study 212 EN Daisaku Morimoto Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yosuke Washio Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kei Tamai Division of Neonatology, Okayama Medical Center, National Hospital Organization Takeshi Sato Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoka Okamura Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Watanabe Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yu Fukushima Division of Neonatology, Okayama Medical Center, National Hospital Organization Junko Yoshimoto Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Misao Kageyama Division of Neonatology, Okayama Medical Center, National Hospital Organization Kenji Baba Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Tsukahara Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Histidine-rich glycoprotein (HRG) has been reported to inhibit signaling leading to the release of high mobility group box 1 protein, a damage-associated molecular pattern. The present study aimed to determine the longitudinal change in HRG levels in extremely preterm infants and assess whether complications such as bronchopulmonary dysplasia (BPD) were associated with differences in HRG levels. In this multicenter, prospective, observational study, we measured serum HRG levels every 2 weeks from birth to 8 weeks of age. Serum HRG was measured using an enzyme-linked immunosorbent assay. We included 19 extremely preterm infants in the study and 74 samples were analyzed. The median gestational age was 26.0 weeks, and the median birth weight was 858 g. Serum HRG levels showed a significant upward trend after birth (p < 0.001); median HRG concentrations at birth and at 2, 4, 6, and 8 weeks of age were 1.07, 1.11, 2.86, 6.05, and 7.49 mu g/mL, respectively. Onset of BPD was not associated with differences in serum HRG levels. Further, the serum HRG levels increased significantly after birth in extremely preterm infants. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 0038-0768 69 2 2023 Greenhouse gas emissions from agricultural soil amended with kitchen compost of varying ages 137 147 EN Tran Thi Minh Chau Graduate School of Environmental and Life Science, Okayama University Takashi Someya Faculty of Agriculture, Saga University Satoshi Akao Faculty of Science and Engineering, Doshisha University Masato Nakamura Institute for Rural Engineering, NARO Fumiko Oritate Institute for Rural Engineering, NARO Hiroaki Somura Graduate School of Environmental and Life Science, Okayama University Shinzo Yamane Faculty of Agriculture and Marine Science, Kochi University Morihiro Maeda Graduate School of Environmental and Life Science, Okayama University Although the use of kitchen waste compost is very common, GHG emissions from soil amended with kitchen waste compost have not been studied. This study aimed to determine the effects of kitchen compost age and application rates on GHG emissions to identify optimal compost management. Soil samples mixed with kitchen waste compost at three different ages: 1 month (1M), 2 months (2M), and 3 months (3M) at two application rates (1% and 2% w/w) were incubated at 25 degrees C for 28 days under aerobic conditions. Emissions of nitrous oxide (N2O), carbon dioxide (CO2), and methane (CH4) were determined on days 3, 7, 14, 21, and 28. Results showed that N2O and CO2 emissions decreased with compost age (p < 0.05). Increased application rates of compost led to increased CO2 emissions and suppression of N2O emissions. Furthermore, CH4 was emitted from soil amended with kitchen compost even under aerobic conditions. This study suggests that 3M kitchen waste compost is optimal in terms of GHG emissions upon application to soil under aerobic conditions. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1341-321X 29 1 2022 Examining the association between vaccine reactogenicity and antibody titer dynamics after the third dose of BNT162b2 vaccine using a mixed-effects model 39 42 EN Naomi Matsumoto Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Nakayama Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University Masanori Furukawa Clinical Laboratory, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Soshi Takao Department of Epidemiology, 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 Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: To mitigate the COVID-19 pandemic, many countries have recommended the use of booster vac-cinations. The relationship between the degree of adverse vaccine reactions and elevated antibody titers is of interest; however, no studies have investigated the temporal changes in antibody titers based on repeated measurements after a third dose of the BNT162b2 vaccine. Methods: This prospective longitudinal cohort study was conducted with 62 healthcare workers who received a third dose of the BNT162b2 at Okayama University Hospital, Japan. Venous blood draw and fingertip whole blood test sample collection were conducted at the early (3-13 days) and 1-month time points; only FWT sample collection was conducted at the 2-month time point. Information on adverse reactions within 1 week after vaccination was also obtained. The association between fever of 37.5 degrees C or higher and antibody titers after the third dose of BNT162b2 was examined using a mixed-effects model and Poisson regression with robust variance. Results: A trend toward higher antibody titers in the early period after vaccination was observed in the febrile individuals, but the differences were not significant at 1 and 2 months post-vaccination (the partial regression coefficient for fever was 8094.3 [-1910.2, 18,098.8] at 1 month after vaccination, and 1764.1 [-4133.9, 7662.1] at 2 months after vaccination in the adjusted models). Conclusion: The findings suggest that the presence of fever after the third vaccine does not predict a sustained elevation in serum antibody titers. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2399-3669 5 1 2022 High-resolution spectroscopy of buffer-gas-cooled phthalocyanine 161 EN Yuki Miyamoto Research Institute for Interdisciplinary Science, Okayama University Reo Tobaru Research Institute for Interdisciplinary Science, Okayama University Yuiki Takahashi Division of Physics, Mathematics, and Astronomy, California Institute of Technology Ayami Hiramoto Research Institute for Interdisciplinary Science, Okayama University Kana Iwakuni Institute for Laser Science, University of Electro-Communications Susumu Kuma Atomic, Molecular and Optical Physics Laboratory, RIKEN Katsunari Enomoto 5Department of Physics, University of Toyama Masaaki Baba Molecular Photoscience Research Center, Kobe University For over five decades, studies in the field of chemical physics and physical chemistry have primarily aimed to understand the quantum properties of molecules. However, high-resolution rovibronic spectroscopy has been limited to relatively small and simple systems because translationally and rotationally cold samples have not been prepared in sufficiently large quantities for large and complex systems. In this study, we present high-resolution rovibronic spectroscopy results for large gas-phase molecules, namely, free-base phthalocya-nine (FBPc). The findings suggest that buffer-gas cooling may be effective for large molecules introduced via laser ablation. High-resolution electronic spectroscopy, combined with other experimental and theoretical studies, will be useful in understanding the quantum properties of molecules. These findings also serve as a guide for quantum chemical calculations of large molecules. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-4409 11 22 2022 Natural Cross-Kingdom Spread of Apple Scar Skin Viroid from Apple Trees to Fungi 3686 EN Mengyuan Tian State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University Shuang Wei State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University Ruiling Bian State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University Jingxian Luo State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University Haris Ahmed Khan State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University Huanhuan Tai College of Agronomy, Northwest A&F University Hideki Kondo Institute of Plant Science and Resources, Okayama University Ahmed Hadidi U.S. Department of Agriculture, Agricultural Research Service Ida Bagus Andika College of Plant Health and Medicine, Qingdao Agricultural University Liying Sun Institute of Plant Science and Resources, Okayama University Viroids are the smallest known infectious agents that are thought to only infect plants. Here, we reveal that several species of plant pathogenic fungi that were isolated from apple trees infected with apple scar skin viroid (ASSVd) carried ASSVd naturally. This finding indicates the spread of viroids to fungi under natural conditions and further suggests the possible existence of mycoviroids in nature. A total of 117 fungal isolates were isolated from ASSVd-infected apple trees, with the majority (85.5%) being an ascomycete Alternaria alternata and the remaining isolates being other plant-pathogenic or -endophytic fungi. Out of the examined samples, viroids were detected in 81 isolates (69.2%) including A. alternata as well as other fungal species. The phenotypic comparison of ASSVd-free specimens developed by single-spore isolation and ASSVd-infected fungal isogenic lines showed that ASSVd affected the growth and pathogenicity of certain fungal species. ASSVd confers hypovirulence on ascomycete Epicoccum nigrum. The mycobiome analysis of apple tree-associated fungi showed that ASSVd infection did not generally affect the diversity and structure of fungal communities but specifically increased the abundance of Alternaria species. Taken together, these data reveal the occurrence of the natural spread of viroids to plants; additionally, as an integral component of the ecosystem, viroids may affect the abundance of certain fungal species in plants. Moreover, this study provides further evidence that viroid infection could induce symptoms in certain filamentous fungi. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1996-1944 15 21 2022 Does Multifunctional Acrylate's Addition to Methacrylate Improve Its Flexural Properties and Bond Ability to CAD/CAM PMMA Block? 7564 EN Yukinori Maruo Department of Prosthodontics, Okayama University Kumiko Yoshihara Health Research Institute, National Institute of Advanced Industrial Science and Technology Masao Irie Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Takuya Matsumoto Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shogo Minagi Department of Prosthodontics, Okayama University This study investigated the effects of a multifunctional acrylate copolymer-Trimethylolpropane Triacrylate (TMPTA) and Di-pentaerythritol Polyacrylate (A-DPH)-on the mechanical properties of chemically polymerized acrylic resin and its bond strength to a CAD/CAM polymethyl methacrylate (PMMA) disk. The methyl methacrylate (MMA) samples were doped with one of the following comonomers: TMPTA, A-DPH, or Trimethylolpropane Trimethacrylate (TMPTMA). The doping ratio ranged from 10 wt% to 50 wt% in 10 wt% increments. The flexural strength (FS) and modulus (FM) of PMMA with and without comonomer doping, as well as the shear bond strength (SBS) between the comonomer-doped PMMA and CAD/CAM PMMA disk, were evaluated. The highest FS (93.2 +/- 4.2 MPa) was obtained when doped with 20 wt% of TMPTA. For TMPTMA, the FS decreased with the increase in the doping ratio. For SBS, TMPTA showed almost constant values (ranging from 7.0 to 8.2 MPa) regardless of the doping amount, and A-DPH peaked at 10 wt% doping (8.7 +/- 2.2 MPa). TMPTMA showed two peaks at 10 wt% (7.2 +/- 2.6 MPa) and 40 wt% (6.5 +/- 2.3 MPa). Regarding the failure mode, TMPTMA showed mostly adhesive failure between the CAD/CAM PMMA disk and acrylic resin while TMPTA and A-DPH showed an increased rate of cohesive or mixed failures. Acrylate's addition as a comonomer to PMMA provided improved mechanical properties and bond strength to the CAD/CAM PMMA disk. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1341-321X 28 12 2022 Detection of Enterobacter cloacae complex strain with a blaNDM-1-harboring plasmid from an elderly resident at a long-term care facility in Okayama, Japan 1697 1699 EN Kazuyoshi Gotoh Department of Bacteriology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Haruto Yamada Department of Clinical Laboratory, Okayama City Hospital Osamu Matsushita Department of Bacteriology, 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 Amidst the global spread of antimicrobial resistance, New Delhi metallo-beta-lactamase (NDM)-type carbapenemase-producing Enterobacterales (CPE) remain uncommon in Japan, and the detection of such highly drug-resistant organisms is limited to inbound cases. There is little evidence regarding the prevalence of NDM beta-lactamase gene (blaNDM)-harboring CPE in the domestic community, especially in the provincial cities of Japan. Herein, we report the isolation of a blaNDM-1-harboring plasmid in Enterobacter cloacae complex strain isolated from an elderly woman without a history of traveling abroad who had resided in a long-term care facility in Okayama, Japan. The multidrug-resistant blaNDM-harboring CPE isolate was detected in a stool sample of the patient during routine screening at admission. We performed whole-genome sequencing analysis of the isolate using MiSeq (Illumina) and MinION (Oxford Nanopore Technologies) platforms. The isolate was identified as sequence type 171, which has predominantly been reported in the United States and China. The blaNDM-1 gene was encoded on the 46,161 bp IncX3 plasmid, with sequence similarity to plasmids of similar size isolated from individuals in China. Collectively, the genomic data suggest that an imported CPE isolate may have spread among healthy individuals in the regional area of Japan. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 2235-2988 12 2022 Features of the oral microbiome in Japanese elderly people with 20 or more teeth and a non-severe periodontal condition during periodontal maintenance treatment: A cross-sectional study 957890 EN Naoki Toyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aya Yokoi Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daiki Fukuhara Department of Preventive Dentistry, Okayama University Hospital Md Monirul Islam Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nanami Sawada Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yukiho Nakashima Department of Preventive Dentistry, Okayama University Hospital Momoko Nakahara Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ichiro Sumita Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Manabu Morita Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Introduction The aim of the present study was to characterize the profile and diversity of the oral microbiome of a periodontally non-severe group with >= 20 teeth in comparison with a severe periodontitis group of elderly Japanese people. Methods A total of 50 patients who had >= 20 teeth and aged >= 60 years were recruited, and 34 participants (13 non-severe participants) were analyzed. After oral rinse (saliva after rinsing) sample collection, the V3-V4 regions of the 16S rRNA gene were sequenced to investigate microbiome composition, alpha diversity (Shannon index, Simpson index, richness, and evenness), and beta diversity using principal coordinate analysis (PCoA) based on weighted and unweighted UniFrac distances. A linear discriminant analysis effect size was calculated to identify bacterial species in the periodontally non-severe group. Results The periodontally non-severe group showed lower alpha diversity than that of the severe periodontitis group (p <0.05); however, the beta diversities were not significantly different. A higher relative abundance of four bacterial species (Prevotella nanceiensis, Gemella sanguinis, Fusobacterium periodonticum, and Haemophilus parainfluenzae) was observed in the non-severe group than that in the severe periodontitis group. Conclusion The oral microbiome in elderly Japanese people with >= 20 teeth and a non-severe periodontal condition was characterized by low alpha diversity and the presence of four bacterial species. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1341-321X 28 11 2022 High frequency of extended-spectrum beta-lactamase-producing Enterobacteriaceae carriers at a Japanese long-term care hospital 1578 1581 EN Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuji Onishi Clinical Laboratory, Marugame Medical Center Natsumi Shinohara Clinical Laboratory, Marugame Medical Center Mayumi Tokuyasu Department of Nursing, Marugame Medical Center Aki Imanishi Department of Nursing, Marugame Medical Center Shinnosuke Fukushima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Lutfun Nahar Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction: Long-term care hospitals (LTCHs) are at a high risk for the inflow and spread of antimicrobial resistance (AMR) pathogens. However, owing to limited laboratory resources, little is known about the extent to which AMR organisms are endemic. Methods: We performed active surveillance for carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in newly admitted patients at Marugame Medical Center, a nearly 200-bedded LTCH located in Kagawa, Japan. From August to December 2021, we tested stool samples from patients wearing diapers and confirmed the genetic variants using specific PCR assays. We also collected clinical variables and compared them between AMR carriers and non-carriers. Results: Stool samples were collected from 75 patients, with a median age of 84 years. CRE strain was not detected, but 37 strains of ESBL-E were isolated from 32 patients (42.7%). During the study period, 4.9% of in-hospital patients (37 per 756 patients) were identified to be ESBL-E carriers in the routine microbiological processing, suggesting that active surveillance detected approximately 9-fold more ESBL-E carriers. The bla(CTM-M-9) group was the most common (38.5%), followed by the bla(TEM) (26.9%). The clinical backgrounds of the ESBL-E non-carriers and carriers were not significantly different. Conclusion: Our active screening demonstrated that nearly half of the patients hospitalized or transferred to a Japanese LTCH were colonized with ESBL-E. We highlight the enforcement of universal basic infection prevention techniques at LTCHs where patients carrying AMR pathogens gather. No potential conflict of interest relevant to this article was reported.

Japanese Society of Veterinary Science Acta Medica Okayama 0916-7250 84 7 2022 Screening of bacterial DNA in bile sampled from healthy dogs and dogs suffering from liver- or gallbladder-associated disease 1019 1022 EN Sakurako NEO School of Veterinary Medicine, Azabu University Iyo TAKEMURA-UCHIYAMA Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Jumpei UCHIYAMA Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hironobu MURAKAMI School of Veterinary Medicine, Azabu University Ayaka SHIMA Anicom Specialty Medical Institute Inc. Hideki KAYANUMA School of Veterinary Medicine, Azabu University Taiki YOKOYAMA School of Veterinary Medicine, Azabu University Satoshi TAKAGI School of Veterinary Medicine, Azabu University Eiichi KANAI School of Veterinary Medicine, Azabu University Masaharu HISASUE School of Veterinary Medicine, Azabu University Although the biliary system is generally aseptic, gallbladder microbiota has been reported in humans and some animals apart from dogs. We screened and analyzed the bacterial deoxyribonucleic acid in canine gallbladders using bile sampled from 7 healthy dogs and 52 dogs with liver- or gallbladder-associated disease. PCR screening detected bacteria in 17.3% of diseased dogs (9/52) and none in healthy dogs. Microbiota analysis of PCR-positive samples showed that the microbial diversity differed between liver- and gallbladder-associated disease groups. Thus, a specific bacterial community appears to occur at a certain frequency in the bile of diseased dogs. No potential conflict of interest relevant to this article was reported.

Frontiers Media S.A. Acta Medica Okayama 1664-462X 13 2022 Time-series transcriptome of Brachypodium distachyon during bacterial flagellin-induced pattern-triggered immunity 1004184 EN Tsubasa Ogasahara Graduate School of Environmental and Life Science, Okayama University Yusuke Kouzai Graduate School of Environmental and Life Science, Okayama University Megumi Watanabe Graduate School of Environmental and Life Science, Okayama University Akihiro Takahashi Graduate School of Environmental and Life Science, Okayama University Kotaro Takahagi Kihara Institute for Biological Research, Yokohama City University June-Sik Kim Bioproductivity Informatics Research Team, RIKEN Center for Sustainable Resource Science Hidenori Matsui Graduate School of Environmental and Life Science, Okayama University Mikihiro Yamamoto Graduate School of Environmental and Life Science, Okayama University Kazuhiro Toyoda Graduate School of Environmental and Life Science, Okayama University Yuki Ichinose Graduate School of Environmental and Life Science, Okayama University Keiichi Mochida Bioproductivity Informatics Research Team, RIKEN Center for Sustainable Resource Science Yoshiteru Noutoshi Graduate School of Environmental and Life Science, Okayama University Plants protect themselves from microorganisms by inducing pattern-triggered immunity (PTI) via recognizing microbe-associated molecular patterns (MAMPs), conserved across many microbes. Although the MAMP perception mechanism and initial events during PTI have been well-characterized, knowledge of the transcriptomic changes in plants, especially monocots, is limited during the intermediate and terminal stages of PTI. Here, we report a time-series high-resolution RNA-sequencing (RNA-seq) analysis during PTI in the leaf disks of Brachypodium distachyon. We identified 6,039 differentially expressed genes (DEGs) in leaves sampled at 0, 0.5, 1, 3, 6, and 12 hours after treatment (hat) with the bacterial flagellin peptide flg22. The k-means clustering method classified these DEGs into 10 clusters (6 upregulated and 4 downregulated). Based on the results, we selected 10 PTI marker genes in B. distachyon. Gene ontology (GO) analysis suggested a tradeoff between defense responses and photosynthesis during PTI. The data indicated the recovery of photosynthesis started at least at 12 hat. Over-representation analysis of transcription factor genes and cis-regulatory elements in DEG promoters implied the contribution of 12 WRKY transcription factors in plant defense at the early stage of PTI induction. No potential conflict of interest relevant to this article was reported.

Frontiers Media S.A. Acta Medica Okayama 1663-9812 13 2022 Anxiolytic-like effects of hochuekkito in lipopolysaccharide-treated mice involve interleukin-6 inhibition 890048 EN Soichiro Ushio Department of Pharmacy, Okayama University Hospital Yudai Wada Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuki Nakamura Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daiki Matsumoto Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kota Hoshika Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoya Shiromizu Department of Pharmacy, Okayama University Hospital Naohiro Iwata Department of Pharmacy, Okayama University Hospital Satoru Esumi Department of Pharmacy, Okayama University Hospital Makoto Kajizono Department of Pharmacy, Okayama University Hospital Yoshihisa Kitamura Department of Pharmacy, Okayama University Hospital Toshiaki Sendo Department of Pharmacy, Okayama University Hospital Hochuekkito (HET) is a Kampo medicine used to treat postoperative and post-illness general malaise and decreased motivation. HET is known to regulate immunity and modulate inflammation. However, the precise mechanism and effects of HET on inflammation-induced central nervous system disorders remain unclear. This study aimed to assess the effect of HET on inflammation-induced anxiety-like behavior and the mechanism underlying anxiety-like behavior induced by lipopolysaccharide (LPS). Institute of Cancer Research mice were treated with LPS (300 mu g/kg, intraperitoneally), a bacterial endotoxin, to induce systemic inflammation. The mice were administered HET (1.0 g/kg, orally) once a day for 2 weeks before LPS treatment. The light-dark box test and the hole-board test were performed 24 h after the LPS injection to evaluate the effects of HET on anxiety-like behaviors. Serum samples were obtained at 2, 5, and 24 h after LPS injection, and interleukin-6 (IL-6) levels in serum were measured. Human and mouse macrophage cells (THP-1 and RAW264.7 cells, respectively) were used to investigate the effect of HET on LPS-induced IL-6 secretion. The repeated administration of HET prevented anxiety-like behavior and decreased serum IL-6 levels in LPS-treated mice. HET significantly suppressed LPS-induced IL-6 secretion in RAW264.7 and THP-1 cells. Similarly, glycyrrhizin, one of the chemical constituents of HET, suppressed LPS-induced anxiety-like behaviors. Our study revealed that HET ameliorated LPS-induced anxiety-like behavior and inhibited IL-6 release in vivo and in vitro. Therefore, we postulate that HET may be useful against inflammation-induced anxiety-like behavior. No potential conflict of interest relevant to this article was reported.

Lippincott Williams & Wilkins Acta Medica Okayama 0025-7974 101 34 2022 Site-specific differences in T lymphocyte composition of the gastric mucosa after Helicobacter pylori eradication e30241 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takahide Takahashi Division of Medical Support, Okayama University Hospital Natsuki Watanabe Division of Medical Support, Okayama University Hospital Makoto Abe Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Sakae Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshiyasu Kono Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiromitsu Kanzaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, 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 Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, Okayama University Hospital Hiroyuki Yanai Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences In our earlier work, we revealed that inflammation of the lesser curvature of the gastric body and antrum could constitute independent risk factors for gastric cancer development, while inflammation of the greater curvature was not. The aims of this study were as follows: first, to reveal the differences between T lymphocyte populations of the gastric antrum and the greater and lesser curvatures of the gastric body in patients after Helicobacter pylori eradication; second, to analyze the correlation between the composition of the stomach-resident T lymphocytes and time from H. pylori eradication; and third, to evaluate the sex differences in T lymphocyte subsets after H. pylori eradication. To investigate site-specific differences in stomach-resident T lymphocytes after H. pylori eradication, we performed flow cytometry analysis on samples taken from the gastric antrum, greater curvature of the gastric body, and lesser curvature of the gastric body of 20 patients. We also analyzed the correlation between the composition of the stomach-resident T lymphocytes and the time from H. pylori eradication. The lymphocyte subsets of the antrum and lesser curvature of the body were similar. In contrast, compared to those in the greater curvature of the gastric body, CD4(+)/CD3(+) lymphocyte subsets (43.8 +/- 19.4% vs 31.7 +/- 14.6%) were elevated in the lesser curvature of the body, whereas CD8(+)/CD3(+) (67.1 +/- 21.3% vs 80.4 +/- 12.0%), CD7(+)/CD3(+) (91.2 +/- 4.6% vs 93.7 +/- 3.8%), CCR4(+)/CD3(+) (7.7 +/- 8.1% vs 10.4 +/- 7.0%), CD45RA(+)/CD3(+)CD4(+) (27.2 +/- 24.8% vs 39.5 +/- 20.8%), and CD45RA(+)/CD3(+)CD4(-) (14.2 +/- 11.1% vs 18.7 +/- 11.5) were lower. Linear regression analysis showed a negative correlation between the time after H. pylori eradication and CD4(+)/CD3(+) (P < .05, R-2 = 0.198). There were no significant differences between men and women with respect to the lymphocyte populations. These results indicate that there are site-specific differences in lymphocyte composition in the stomach after H. pylori eradication. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 Gene Expression Profiling between Patient Groups with High and Low Ki67 Levels after Short-term Preoperative Aromatase Inhibitor Treatment for Breast Cancer 399 408 EN Yukiko Kajiwara Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Iwamoto Departments of Breast and Endocrine Surgery, Okayama University Hospital Yidan Zhu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mariko Kochi Departments of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Departments of Breast and Endocrine Surgery, Okayama University Hospital Naruto Taira Departments of Breast and Endocrine Surgery, Okayama University Hospital Hiroyoshi Doihara Departments of Breast and Endocrine Surgery, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/63894 According to a recent report, a low Ki67 level after short-term preoperative hormone therapy (post-Ki67) might suggest a more favorable prognosis compared with a high post-Ki67 level in patients with hormone receptorpositive/human epidermal growth factor 2-negative (HR+/HER2−) breast cancer with high levels of Ki67. This study aimed to evaluate the pre-treatment genetic differences between these two patient groups. Forty-five luminal B-like patients were stratified into two groups, namely, a group with high (H→H) and one with low (H→L) Ki67 levels after short-term preoperative aromatase inhibitor (AI) treatment. We compared pre-treatmentgene expression profiles between the two groups. In gene level analysis, there was no significant difference between the two groups by the class comparison test. In pathway analysis, five metabolism-related gene sets were significantly upregulated in the H→L group (p≤0.05). In the search for novel targets, five genes (PARP, BRCA2, FLT4, CDK6, and PDCD1LG2) showed significantly higher expression in the H→H group (p≤0.05). Several metabolism-related pathways were associated with sensitivity to AI. In the future, it will be necessary to seek out new therapeutic strategies for the poor prognostic group with high post-Ki67. No potential conflict of interest relevant to this article was reported.