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

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

MDPI AG Acta Medica Okayama 2076-2607 14 4 2026 The Role of Nitrate-Reducing Bacteria Isolated from Helicobacter pylori-Infected Individuals in Gastric Cancer Development 760 EN Serika Kuwagi Department of Bacteriology, Academic Field of Health Sciences, Okayama University Kazuyoshi Gotoh Department of Bacteriology, Academic Field of Health Sciences, Okayama University Marina Komatsubara Department of Bacteriology, Academic Field of Health Sciences, Okayama University Shuma Tsuji Department of Bacteriology, Academic Field of Health Sciences, Okayama University Shyoutarou Okanoue Department of Gastroenterology and Hepatology, Academic Field of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Okada Himeji Red Cross Hospital Jumpei Uchiyama Department of Bacteriology, Academic Field of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Akari Watanabe Department of Oral Health Care and Rehabilitation, Institute of Biomedical Sciences, Graduate School, Tokushima University Kenji Yokota Department of Bacteriology, Academic Field of Health Sciences, Okayama University Helicobacter pylori is a Gram-negative bacterium that inhabits the gastric mucosa, with a global prevalence in humans of approximately 40%. It is likely the cause of 90% of gastric cancer (GC) cases and thus considered the most prominent driver of GC development. However, during gastric mucosal atrophy, other bacteria such as nitrate-reducing bacteria (NRB) also proliferate. In this study, we isolated NRB from patients with gastritis and GC to examine their effects on the epithelial cell cycle and production of various cytokines in monocytic cell lines. Bacterial counts (excluding H. pylori and NRB) increased with the progression of gastric mucosal atrophy and were significantly higher in patients with GC. Gastric epithelial cell lines were stimulated with isolated NRB, and the proportion of cells in each cell cycle was measured. Strains from patients with open-type gastritis progressed more rapidly through cell cycles than those from patients with GC. NRB isolated from gastric cancer had high nitrate-reducing activity. Thus, NRB may contribute to GC progression during H. pylori-induced carcinogenesis. Therefore, evaluating gastric atrophy and microbiota may be important for managing the risk of GC. 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 2025 年度における「先進病院実習」の取り組み 49 57 EN Mizuki MORITA Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masaki MAGARI Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jin Wang Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toyohiko WATANABE Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masataka OITA Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Nahoko HARADA Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Keisuke SHISHIDO Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University 10.18926/interdisciplinary/70330 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.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 6 2025 Severe Anemia Caused by a Colorectal Lipoma With Central Erosions: A Case Report e85768 EN Yusuke Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuki Matsumi Department of Gastroenterological Surgery, Okayama University Hospital Ko Watanabe Department of Pathology, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Colorectal lipomas are benign tumors that are often asymptomatic and discovered incidentally. In most cases, they can be managed conservatively with observation. We report the case of a man in his 70s with a colorectal lipoma located in the cecum. An investigation into his severe anemia led to the suspicion that the cecal lipoma was the underlying cause. An ileocecal resection was performed. Erosions were observed at the center of the lipoma. Although small colorectal lipomas are generally asymptomatic and rarely cause anemia, periodic endoscopic examinations are recommended. These lesions should be considered in the differential diagnosis of lower gastrointestinal bleeding. No potential conflict of interest relevant to this article was reported.

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

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 1743-9159 112 2 2025 Total thymectomy is oncologically superior to partial thymectomy in patients with thymic carcinoma: insights from a multicenter real-world data analysis 2301 2310 EN Tatsuya Hayashi 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 Toshiharu Mitsuhashi Center of Innovative Clinical Medicine, Okayama University Hospital Hidetaka Yamamoto Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Habu Okayama University Thoracic Surgery Study Group (OUTSSG) 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 Hiromasa Yamamoto Okayama University Thoracic Surgery Study Group (OUTSSG) Tomoaki Otsuka Okayama University Thoracic Surgery Study Group (OUTSSG) Mototsugu Watanabe Okayama University Thoracic Surgery Study Group (OUTSSG) Takeshi Kurosaki Okayama University Thoracic Surgery Study Group (OUTSSG) Eiji Yamada Okayama University Thoracic Surgery Study Group (OUTSSG) Eisuke Matsuda Okayama University Thoracic Surgery Study Group (OUTSSG) Tatsurou Hayashi Okayama University Thoracic Surgery Study Group (OUTSSG) Toshiya Fujiwara Okayama University Thoracic Surgery Study Group (OUTSSG) Makio Hayama Okayama University Thoracic Surgery Study Group (OUTSSG) Hiroyuki Tao Okayama University Thoracic Surgery Study Group (OUTSSG) Masaomi Yamane Okayama University Thoracic Surgery Study Group (OUTSSG) Hidetoshi Inokawa Okayama University Thoracic Surgery Study Group (OUTSSG) Yuji Hirami Okayama University Thoracic Surgery Study Group (OUTSSG) Kazuhiro Washio Okayama University Thoracic Surgery Study Group (OUTSSG) Takahiko Misao Okayama University Thoracic Surgery Study Group (OUTSSG) Motohiro Yamashita Okayama University Thoracic Surgery Study Group (OUTSSG) Yoshifumi Sano Okayama University Thoracic Surgery Study Group (OUTSSG) Masao Nakata Okayama University Thoracic Surgery Study Group (OUTSSG) Osamu Kawamata Okayama University Thoracic Surgery Study Group (OUTSSG) Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Although total thymectomy has been the standard surgical approach for thymic epithelial tumors, an increasing number of recent reports suggest that partial thymectomy for early-stage thymomas may yield outcomes comparable to those of total thymectomy. However, whether partial thymectomy is a viable alternative for thymic carcinoma remains unclear.<br> Materials and methods: A total of 106 patients with thymic carcinoma underwent curative intended resection at 19 institutions between January 2010 and December 2021. Excluding 14 patients with incomplete resection, 92 patients with thymic carcinoma who underwent total (n = 73) or partial thymectomy (n = 19) were compared. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan–Meier curves and Cox proportional hazard models. Overlap weighting was applied to adjust for potential confounding factors.<br> Results: Among patients with clinical stage I disease, 79.3% were upstaged to stage II or higher postoperatively. Unadjusted analyses revealed no statistically significant differences in OS and RFS between the total and partial thymectomy groups, although a trend toward poorer outcomes in the partial thymectomy group was observed. After overlap weighting, partial thymectomy was associated with significantly poorer OS (P = 0.0027) and higher recurrence risk (P < 0.0001). Early postoperative recurrence occurred more frequently in the partial thymectomy group.<br> Conclusion: Partial thymectomy was associated with significantly worse survival and recurrence outcomes in thymic carcinoma. Given the limitations of preoperative diagnosis, total thymectomy should remain the preferred surgical approach for undiagnosed thymic epithelial tumors to achieve optimal oncologic control and minimize the risk of recurrence. No potential conflict of interest relevant to this article was reported.

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

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

Wiley Acta Medica Okayama 0001-690X 153 3 2026 Impact of Schizophrenia Spectrum Disorders on the Receipt of Invasive and Systemic Therapy for Colorectal Cancer: A Nationwide Multicenter Retrospective Cohort Study in Japan 191 199 EN Masaki Fujiwara Department of Neuropsychiatry, Medical Development Field, Okayama University Yuto Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Taisuke Ishii Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center Tomone Watanabe Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center Maiko Fujimori Division of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer Center Naoki Nakaya Tohoku Medical Megabank Organization, Tohoku University Toshihiko Kawamura Department of Medical Informatics, Shimane University Hospital Koji Otsuki Department of Psychiatry, Faculty of Medicine, Shimane University Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Medical Development Field, Okayama University Taichi Shimazu Division of Behavioral Sciences, National Cancer Center Institute for Cancer Control, National Cancer Center Shiro Hinotsu Department of Biostatistics and Data Management, Sapporo Medical University Yosuke Uchitomi Department of Cancer Survivorship and Digital Medicine, The Jikei University School of Medicine Masatoshi Inagaki Department of Psychiatry, Faculty of Medicine, Shimane University Introduction: This study examined treatment disparities for colorectal cancer among patients diagnosed with schizophrenia spectrum disorders (SSD), focusing on invasive treatments and stage-appropriate systemic therapy within a universal healthcare system.<br> Method: In this nationwide retrospective cohort study (2018–2021), we identified 248,966 colorectal cancer patients, including 2337 diagnosed with SSD, using linked cancer registry and insurance claims data in Japan. The presence of SSD was classified according to ICD-10 codes F20–29. We used multivariable logistic regression to compare the odds of receiving stage-appropriate adjuvant chemotherapy and systemic therapy, as well as the odds of receiving surgical or endoscopic treatments, between the two groups. The analysis adjusted for age, sex, clinical stage, and scores on the Charlson Comorbidity Index and Barthel Index.<br> Results: The clinical stage distribution at diagnosis for colorectal cancer differed significantly between patients with SSD and those without psychiatric disorders (p < 0.001). After adjusting for clinical stage and other covariates, patients with SSD demonstrated significantly lower odds of receiving surgical or endoscopic treatment (adjusted odds ratio [aOR], 0.83; 95% CI, 0.73–0.94). The disparities were more pronounced for systemic therapy; patients with SSD had substantially lower odds of receiving adjuvant chemotherapy for stage III disease (aOR, 0.33; 95% CI, 0.26–0.41) and systemic therapy for stage IV disease (aOR, 0.23; 95% CI, 0.17–0.31).<br> Conclusion: Patients with SSD encounter substantial disparities in accessing standard colorectal cancer care, particularly systemic therapies. These findings highlight the urgent need for interventions to ensure equitable cancer treatment for this vulnerable population. No potential conflict of interest relevant to this article was reported.

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

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

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

SAGE Publications Acta Medica Okayama 0963-6897 35 2026 Addition of human platelet lysate to islet culture medium suppresses islet loss and improves transplantation outcomes EN Hirofumi Noguchi Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus Chika Miyagi-Shiohira Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Issei Saitoh Department of Pediatric Dentistry, Asahi University School of Dentistry No potential conflict of interest relevant to this article was reported.

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

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

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

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

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

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

Wiley Acta Medica Okayama 2050-0904 13 2 2025 Maturity-Onset Diabetes of the Young (MODY) With HNF1B p.Glu105Lys Mutation Achieving Significant Insulin Reduction on Tirzepatide: A Case Report e70173 EN Mihiro Sue Department of Diabetology and Metabolism, NHO Okayama Medical Center Mayu Watanabe Department of Diabetology and Metabolism, NHO Okayama Medical Center Ayumi Inoue Department of Diabetology and Metabolism, NHO Okayama Medical Center Akihiro Katayama Department of Diabetology and Metabolism, NHO Okayama Medical Center Sanae Teshigawara Department of Internal Medicine, Diabetes Center, Okayama Saiseikai General Hospital Yuichi Matsushita Department of Diabetology and Metabolism, NHO Okayama Medical Center Masaya Takeda Department of Diabetology and Metabolism, NHO Okayama Medical Center Izumi Iseda Department of Diabetology and Metabolism, NHO Okayama Medical Center Jun Eguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kazuyuki Hida Department of Diabetology and Metabolism, NHO Okayama Medical Center This report describes the first case of maturity-onset diabetes in young (MODY) with HNF1B mutation started administration of the dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, tirzepatide. A 26-year-old female with a 15-year history of diabetes mellitus was diagnosed with MODY, which is characterized by decreased insulin secretion. She was treated with tirzepatide, which significantly improved her glycemic management; insulin secretion increased the fasting serum C-peptide immunoreactivity from 0.36 to 1.09 ng/mL. The patient discontinued glimepiride, and her total daily insulin dose was reduced from 88 to 4 units. This report highlights the glucose-lowering effects of tirzepatide in a patient with MODY who has the HNF1B p.Glu105Lys mutation. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0897-3806 38 2 2025 Ethical Use of Cadaveric Images in Anatomical Textbooks, Atlases, and Journals: A Consensus Response From Authors and Editors 222 225 EN Joe Iwanaga Department of Neurosurgery, Tulane University School of Medicine Hee‐Jin Kim Division in Anatomy & Development Biology, Department of Oral Biology, Yonsei University College of Dentistry Keiichi Akita Department of Clinical Anatomy, Tokyo Medical and Dental University (TMDU) Bari M. Logan UK Ralph T. Hutchings UK Nicolás Ottone Department of Integral Adult Dentistry, Center for Research in Dental Sciences (CICO), Dental School, Universidad de La Frontera Yoichi Nonaka Department of Neurosurgery, Tokai University School of Medicine Mahindra Anand Department of Anatomy, Rama Medical College & Research Centre Danny Burns Department of Anatomical Sciences, School of Medicine, St. George's University Vishram Singh Department of Anatomy, Kasturba Medical College Mangalore, Manipal Academy of Higher Education Maria Peris‐Celda Department of Neurologic Surgery, Mayo Clinic Francisco Martinez‐Soriano Department of Anatomy, University of Valencia Nihal Apaydin Department of Anatomy, Faculty of Medicine, Ankara University Amgad Hanna Department of Neurological Surgery, University of Wisconsin Nobutaka Yoshioka Department of Neuroplastic and Reconstructive Surgery Social Medical Corporation Kotobukikai Tominaga Hospital Juan Fernandez‐Miranda Department of Neurosurgery, Stanford University School of Medicine Mi‐Sun Hur Department of Anatomy, Daegu Catholic University School of Medicine Mohammadali M. Shoja Department of Medical Education, Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University (NSU) Farhood Saremi Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Ronald Reagan UCLA Medical Center Francisco Reina Medical Sciences Department, Faculty of Medicine, Clinical Anatomy, Embryology and Neuroscience Research Group, University of Girona Yoko Tabira Division of Gross and Clinical Anatomy, Department of Anatomy, Kurume University School of Medicine Anna Carrera Medical Sciences Department, Faculty of Medicine, Clinical Anatomy, Embryology and Neuroscience Research Group, University of Girona Jonathan D. Spratt University Hospital of North Durham S. Yen Ho Cardiac Morphology, Royal Brompton & Harefield Hospitals Shumpei Mori University of California Los Angeles (UCLA) Cardiac Arrhythmia Center, Cardiovascular and Interventional Programs, UCLA Health System, David Geffen School of Medicine at UCLA Noritaka Komune Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University Koichi Watanabe Division of Gross and Clinical Anatomy, Department of Anatomy, Kurume University School of Medicine Alberto Prats‐Galino Laboratory of Surgical NeuroAnatomy (LSNA), director of the Body Donation and Dissection Rooms Service, Faculty of Medicine and Health of Science, University of Barcelona Jose De Andrés Surgery Specialties Department, University of Valencia Miguel Angel Reina CEU‐San‐Pablo University School of Medicine Peter H. Abrahams Warwick Medical School Robert H. Anderson Biosciences Institute, Newcastle University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Marios Loukas Department of Anatomical Sciences, School of Medicine, St. George's University R. Shane Tubbs Department of Neurosurgery, Tulane University School of Medicine Nowadays, consent to use donor bodies for medical education and research is obtained from the body donors and their families before the donation. Recently, the International Federation of Associations of Anatomists (IFAA) published guidelines that could restrict the appearance of cadaveric images in commercial anatomical resources such as textbooks and other educational products. These guidelines state that the donor must expressly consent to using such images for this purpose. Cadaveric photos and drawings made from dissections of cadavers have been used in anatomy textbooks and atlases for hundreds of years. They are invaluable for anatomy students and clinical/surgical practitioners. The IFAA guidelines should not restrict the use of those older books; to do so would infringe the rights of those seeking knowledge from these resources. As the images in such textbooks and atlases are anonymized and are used for teaching and research, and the donors and their families are informed about this before the donation, we believe no additional consent is needed. It is impossible to separate educational from “commercial” usage entirely in any situation, e.g., publications from publishers and the use of cadavers in medical schools. Therefore, our best efforts to avoid unethical use of cadaveric images by following traditional consent processes are still needed so that more people will reap the benefits from them. As senior textbook/atlas authors/editors from over 10 countries, we believe that using cadaveric images in anatomy textbooks is appropriate, and no additional consent should be necessary. Such usage falls within the good faith of professionals using these invaluable gifts. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2399-3642 8 1 2025 A genome-wide association study identifies the GPM6A locus associated with age at onset in ALS 1720 EN Ryoichi Nakamura Department of Neurology, Aichi Medical University School of Medicine Genki Tohnai Division of ALS Research, Aichi Medical University School of Medicine Naoki Atsuta Department of Neurology, Aichi Medical University School of Medicine Yumi Matsuda Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine Satoru Morimoto Keio University Regenerative Medicine Research Center, Kawasaki Daisuke Ito Department of Neurology, Nagoya University Graduate School of Medicine Masahisa Katsuno Department of Neurology, Nagoya University Graduate School of Medicine Yuishin Izumi Department of Neurology, Tokushima University Graduate School of Biomedical Sciences Mitsuya Morita Division of Neurology, Department of Internal Medicine, Jichi Medical University Ikuko Iwata Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Ichiro Yabe Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Tomoko Nakazato Department of Neurology, Juntendo University School of Medicine Nobutaka Hattori Department of Neurology, Juntendo University School of Medicine Takehisa Hirayama Department of Neurology, Toho University Faculty of Medicine Osamu Kano Department of Neurology, Toho University Faculty of Medicine Asako Tamura Department of Neurology, Mie University Graduate School of Medicine Naoki Suzuki Department of Neurology, Tohoku University Graduate School of Medicine Masashi Aoki Department of Neurology, Tohoku University Graduate School of Medicine Kazumoto Shibuya Department of Neurology, Graduate School of Medicine, Chiba University Satoshi Kuwabara Department of Neurology, Graduate School of Medicine, Chiba University Masaya Oda Department of Neurology, Vihara Hananosato Hospital Rina Hashimoto Department of Neurology, NHO Higashinagoya National Hospital Ikuko Aiba Department of Neurology, NHO Higashinagoya National Hospital Tomohiko Ishihara Department of Neurology, Brain Research Institute, Niigata University Osamu Onodera Department of Neurology, Brain Research Institute, Niigata University Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kota Bokuda Department of Neurology, Tokyo Metropolitan Neurological Hospital Toshio Shimizu Department of Neurology, Tokyo Metropolitan Neurological Hospital Yoshio Ikeda Department of Neurology, Gunma University Graduate School of Medicine Kazuko Hasegawa Division of Neurology, NHO Sagamihara National Hospital Fumiaki Tanaka Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine Takanori Yokota Department of Neurology and Neurological Science, NucleoTIDE and PepTIDE Drug Discovery Center (TIDE), Institute of Science Tokyo Kazuaki Kanai Department of Neurology, Fukushima Medical University School of Medicine Yu-ichi Noto Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Ryuji Kaji Department of Neurology, Tokushima University Graduate School of Biomedical Sciences Hirohisa Watanabe Department of Neurology, Fujita Health University Tomoko Konishi Division of ALS Research, Aichi Medical University School of Medicine Mikiko Hasegawa Division of ALS Research, Aichi Medical University School of Medicine Hozuki Fukaya Division of ALS Research, Aichi Medical University School of Medicine Jun-ichi Niwa Department of Neurology, Aichi Medical University School of Medicine Manabu Doyu Department of Neurology, Aichi Medical University School of Medicine Yohei Okada Department of Neurology, Aichi Medical University School of Medicine Shiho Nakamura Keio University Regenerative Medicine Research Center, Kawasaki Fumiko Ozawa Keio University Regenerative Medicine Research Center, Kawasaki Hideyuki Okano Keio University Regenerative Medicine Research Center, Kawasaki Masahiro Nakatochi Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine Gen Sobue Division of ALS Research, Aichi Medical University School of Medicine Amyotrophic lateral sclerosis (ALS) exhibits considerable clinical variability, such as differences in age at onset (AAO). Multiple factors, including genetic factors, may underlie this variability; however, the specific determinants remain unclear. To identify genes affecting AAO, we have conducted a genome-wide association study in Japanese patients with ALS (discovery cohort: n = 1808; replication cohort: n = 207). Here, we show that the minor A allele of rs113161727 at the ADAM29-GPM6A locus is associated with a younger AAO in the discovery cohort (effect, -4.27 years; p = 4.60 × 10-8); this finding has been confirmed in the replication cohort (p = 0.0068) and meta-analysis (p = 1.08 × 10−9). Among 65 ALS patients with a SOD1 mutation, the AAO has been found to be 10.2 years younger in those with the A allele than in those without it (p = 0.002). This variant correlates with GPM6A upregulation in iPSC-derived motor neurons, suggesting GPM6A as a candidate AAO modifier. Overall, our study highlights the impact of genetic modifiers on ALS heterogeneity and provides a potential target for delaying disease onset. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 MRI Images of a Case of Adenocarcinoma, Human Papillomavirus-Independent, Mesonephric Type, of the Uterine Cervix 463 468 EN Yudai Asano Department of Radiology, Okayama University Hospital Chika Nishihara Department of Radiology, Okayama University Hospital Takahiro Kitayama Department of Radiology, Okayama University Hospital Nanako Okawa Department of Radiology, Okayama University Hospital Satoko Makimoto Department of Radiology, Okayama University Hospital Fumiyo Higaki Department of Radiology, Okayama University Hospital Katsuhide Kojima Department of Radiology, Okayama University Hospital Hanako Sugihara Department of Obstetrics and Gynecology, Okayama University Hospital Naoyuki Ida Department of Obstetrics and Gynecology, Okayama University Hospital Hiroyuki Yanai Department of Pathology, Okayama University Hospital Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Case Report 10.18926/AMO/69850 We present a case of a woman in her 70s who was diagnosed with mesonephric adenocarcinoma of the uterine cervix, following biopsy and surgery. Preoperative MRI revealed a 7-cm, well-defined circumferential cervical mass with left lateral wall predominance, bulging into the uterine cavity and vagina. The lesion showed intermediate signal intensity on T2-weighted images, diffusion restriction, and early contrast enhancement weaker than that of the myometrium, followed by washout on contrast-enhanced imaging. The circumferential growth pattern with the lateral wall predominance and its imaging characteristics may suggest this rare entity be routinely included in the differential diagnosis of cervical cancers. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1556-0864 20 5 2025 Amivantamab Plus Lazertinib in Patients With EGFR-Mutant NSCLC After Progression on Osimertinib and Platinum-Based Chemotherapy: Results From CHRYSALIS-2 Cohort A 651 664 EN Benjamin Besse Paris-Saclay University, Institut Gustave Roussy Koichi Goto National Cancer Center Hospital East Yongsheng Wang Institute of Clinical Trial Center and Cancer Center, West China Hospital, Sichuan University Se-Hoon Lee Samsung Medical Center, Sungkyunkwan University School of Medicine Melina E. Marmarelis University of Pennsylvania, Perelman School of Medicine Yuichiro Ohe National Cancer Center Hospital Reyes Bernabe Caro Hospital Universitario Virgen Del Rocio Dong-Wan Kim Seoul National University College of Medicine and Seoul National University Hospital Jong-Seok Lee Seoul National University College of Medicine and Seoul National University Hospital Sophie Cousin Institut Bergonié Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Yongsheng Li Chongqing University Cancer Hospital Luis Paz-Ares Hospital Universitario 12 de Octubre Akira Ono Shizuoka Cancer Center Rachel E. Sanborn Earle A. Chiles Research Institute, Providence Cancer Institute Naohiro Watanabe Department of Thoracic Oncology, Aichi Cancer Center Hospital Maria Jose de Miguel START Madrid-CIOCC, Hospital HM Sanchinarro Carole Helissey Clinical Research unit, Military Hospital Begin Catherine A. Shu Columbia University Medical Center Alexander I. Spira Virginia Cancer Specialists Pascale Tomasini Aix Marseille University - CNRS, INSERM, CRCM; CEPCM - AP-HM Hopital de La Timone James Chih-Hsin Yang National Taiwan University Cancer Center Yiping Zhang Zhejiang Cancer Hospital Enriqueta Felip Medical Oncology Service, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital Campus, Universitat Autonoma de Barcelona Frank Griesinger Pius-Hospital, University Medicine of Oldenburg Saiama N. Waqar Division of Oncology, Washington University School of Medicine Antonio Calles Hospital General Universitario Gregorio Marañón Joel W. Neal Stanford University Medical Center Christina S. Baik University of Washington, Fred Hutchinson Cancer Center Pasi A. Jänne Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute S. Martin Shreeve Johnson & Johnson Joshua C. Curtin Johnson & Johnson Bharvin Patel Johnson & Johnson Michael Gormley Johnson & Johnson Xuesong Lyu Johnson & Johnson Jun Chen Johnson & Johnson Pei-Ling Chu Johnson & Johnson Janine Mahoney Johnson & Johnson Leonardo Trani Johnson & Johnson Joshua M. Bauml Johnson & Johnson Meena Thayu Johnson & Johnson Roland E. Knoblauch Johnson & Johnson Byoung Chul Cho Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine Introduction: Treatment options for patients with EGFR-mutated NSCLC with disease progression on or after osimertinib and platinum-based chemotherapy are limited.<br> Methods: CHRYSALIS-2 cohort A evaluated amivantamab plus lazertinib in patients with EGFR exon 19 deletion- or L858R-mutated NSCLC with disease progression on or after osimertinib and platinum-based chemotherapy. Primary end point was investigator-assessed objective response rate (ORR). The patients received 1050 mg of intravenous amivantamab (1400 mg if ≥ 80 kg) plus 240 mg of oral lazertinib.<br> Results: In cohort A (N = 162), the investigator-assessed ORR was 28% (95% confidence interval [CI]: 22–36). The blinded independent central review–assessed ORR was 35% (95% CI: 27–42), with a median duration of response of 8.3 months (95% CI: 6.7–10.9) and a clinical benefit rate of 58% (95% CI: 50–66). At a median follow-up of 12 months, 32 of 56 responders (57%) achieved a duration of response of more than or equal to 6 months. Median progression-free survival by blinded independent central review was 4.5 months (95% CI: 4.1–5.8); median overall survival was 14.8 months (95% CI: 12.2–18.0). Preliminary evidence of central nervous system antitumor activity was reported in seven patients with baseline brain lesions and no previous brain radiation or surgery. Exploratory biomarker analyses using next-generation sequencing of circulating tumor DNA revealed responses in patients with and without EGFR- or MET-dependent resistance. The most frequent adverse events were rash (grouped term; 81%), infusion-related reaction (68%), and paronychia (52%). The most common grade greater than or equal to 3 treatment-related adverse events were rash (grouped term; 10%), infusion-related reaction (9%), and hypoalbuminemia (6%).<br> Conclusions: For patients with limited treatment options, amivantamab plus lazertinib demonstrated an antitumor activity with a safety profile characterized by EGFR- or MET-related adverse events, which were generally manageable. 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.<br> 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%.<br> 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).<br> 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 Vesicular Glutamate Transporter 3 Is Involved in Glutamatergic Signalling in Podocytes EN Naoko NISHII Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Somatic mutations in tumor-infiltrating lymphocytes impact on antitumor immunity  EN Fumiaki MUKOHARA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Role of galectin-9 in the development of gestational diabetes mellitus EN ALBUAYJAN HAYA HAMED H Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Hypoglycemia and hyperinsulinemia induced by phenolic uremic toxins in CKD and DKD patients 5762 EN Yoshiyasu Tongu Tohoku University School of Medicine Tomoko Kasahara Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Yasutoshi Akiyama Laboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical Sciences Takehiro Suzuki Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Hsin-Jung Ho Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Yotaro Matsumoto Laboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical Sciences Ryota Kujirai Laboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical Sciences Koichi Kikuchi Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Koji Nata Department of Medical Biochemistry, School of Pharmacy, Iwate Medical University Makoto Kanzaki Department of Biomedical Engineering, Tohoku University Kenshin Suzuki Tohoku University School of Medicine Shun Watanabe Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Chiharu Kawabe Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Yui Miyata Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Shun Itai Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Takafumi Toyohara Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Chitose Suzuki Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Tetsuhiro Tanaka Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Tomioka Laboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical Sciences Takaaki Abe Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine Patients with end-stage renal disease have lower fasting plasma glucose and HbA1c levels, with significantly higher insulin levels. For a long time, it has been believed that this higher insulin level in renal failure is due to decreased insulin clearance caused by reduced renal function. However, here we reported that accumulation of the gut microbiota-derived uremic toxin, phenyl sulfate (PS) in the renal failure, increased insulin secretion from the pancreas by enhanced glucose-stimulated insulin secretion. Other endogenous sulfides compounds which accumulated as in the renal failure also increased glucose-stimulated insulin secretion from β-cell. With RNA-seq analyses and gene knock down, we demonstrated that insulin secretion evoked by PS was mediated by Ddah2. In addition, we also found that PS increased insulin resistance through lncRNA expression and Erk phosphorylation in the adipocytes. To confirm the relationship between PS and glucose metabolism in human, we recruited 2 clinical cohort studies (DKD and CKD) including 462 patients, and found that there was a weak negative correlation between PS and HbA1c. Because these trials did not measure fasting insulin level, we alternatively used the urinary C-peptide/creatinine ratio (UCPCR) as an indicator of insulin resistance. We found that PS may induce insulin resistance in patients with eGFR < 60 mL/min/1.73 m2. These data suggest that the accumulation of uremic toxins modulates glucose metabolism and induced insulin resistance in CKD and DKD patients. Considering HbA1c as a reflection of chronic hyperglycemia and UCPCR as a reflection of chronic hyperinsulinemia, our findings indicate that PS is negatively associated with hyperglycemia independent of CKD, and positively associated with hyperinsulinemia in DKD patients. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 10 2025 Bladder Trigone as a Sensory Hub: A Narrative Review e94951 EN Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Maruyama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Mitsui Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takanori Sekito Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomofumi Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The bladder trigone is an anatomically and functionally distinct region within the lower urinary tract (LUT), characterized by a dense network of afferent sensory fibers, specialized urothelial interactions, and prominent mechanotransduction mechanisms. Its intricate neuroarchitecture enables precise detection of bladder filling and coordination of micturition, whereas dysregulation of these pathways contributes to lower urinary tract symptoms (LUTS), including urgency, frequency, and bladder pain. Despite its recognized clinical relevance, the structural and functional basis of trigonal sensory signaling - and its role - remain incompletely understood.<br> This review synthesizes current evidence on trigonal afferent organization, integrating data from anatomical mapping, receptor profiling, electrophysiological characterization, and translational research. Seminal anatomical observations are combined with recent advances in mechanotransduction and purinergic, peptidergic, and transient receptor potential (TRP) signaling to provide a comprehensive perspective. The trigone exhibits three principal afferent classes: (1) intraepithelial fibers penetrating umbrella cells, marked by P2X purinoceptor 3 (P2X3), transient receptor potential vanilloid 1 (TRPV1), calcitonin gene-related peptide (CGRP), and substance P (SP); (2) subepithelial plexuses surrounding microvasculature, enriched in vasoactive neuropeptides and exhibiting plastic hypertrophy in overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS); and (3) encapsulated corpuscular endings at the lamina propria-detrusor junction, expressing PIEZO1/2 and acid-sensing ion channels (ASICs) for rapid adaptation. In trigeminal dorsal root ganglion (DRG) neurons, high expression of PIEZO2, P2RX3, and voltage-gated sodium channel, type 1.8 (Nav1.8) was observed, revealing their role as the foundation for multisensory information processing. Functional assays highlight distinct mechanotransductive and chemosensory pathways, with aging, inflammation, and neurotrophic factors driving afferent plasticity underlying abnormal bladder sensation, such as urgency, frequency, and pain. Early clinical trials of P2X3 antagonists and intravesical TRPV1 inhibitors demonstrate promising symptomatic benefits. Collectively, evidence positions the bladder trigone as a critical sensory hub where neuronal, urothelial, and immune signals converge to regulate bladder sensation. Understanding its molecular and structural specialization may inform the development of region-specific neuromodulatory therapies targeting sensory urgency and afferent-driven bladder dysfunction. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0006-291X 786 2025 Hydrogen-rich gas enhances mitochondrial membrane potential and respiratory function recovery in Caco-2 cells post-ischemia-reperfusion injury 152753 EN Mizuki Seya Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Aokage Biological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology Ying Meng Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Hirayama Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takafumi Obara Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tsuyoshi Nojima Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosaki Yoshinori Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Yumoto Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Watanabe Department of Emergency, Disaster and Critical Care Medicine, Hyogo Medical University Taihei Yamada Department of Emergency, Disaster and Critical Care Medicine, Hyogo Medical University Hiromichi Naito Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsunori Nakao Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Ischemia-reperfusion (I/R) injury induces oxidative stress, leading to damage in highly susceptible intestinal tissues. Molecular hydrogen (H2) has shown therapeutic potential in I/R injuries, with our prior research showing its efficacy in improving outcomes in rat intestinal transplantation models. However, its impact on mitochondrial function remain insufficiently understood. This study aims to elucidate how H2 modulates mitochondrial function impaired by I/R injury.<br> Methods: To assess the effects of H2 on I/R injury, cells were divided into three groups: a control group, a hypoxic group (99 % N2, 1 % O2, without H2 for 3, 6, or 24 h), and a hypoxic-H2 group (99 % H2, 1 % O2, for the same durations). After treatment, cells were reoxygenated under normoxic conditions (21 % O2) for 1, 2, 4, or 6 h. Mitochondrial membrane potential, oxygen consumption, and ATP production were measured. Reactive oxygen species production and apoptotic and metabolic regulators were also assessed.<br> Results: H2 markedly promoting mitochondrial recovery following I/R injury, by enhancing ATP production, restoring mitochondrial membrane potential, and improving oxygen consumption. It also reduced ROS levels and suppressed pro-apoptotic signaling. Notably, H2 suppressed the expression of HIF1α and PDK1, suggesting that H2 may act upstream of hypoxia-driven signaling pathways. These changes promoted oxidative phosphorylation and overall cellular function during reperfusion.<br> Conclusions: Our findings reveal that H2 therapy supports mitochondrial function, suppresses ROS, and modulates hypoxia-driven pathways in I/R injury. These insights advance the understanding of H2's potential in addressing I/R injury and provide a foundation for its application in other hypoxia-related conditions. No potential conflict of interest relevant to this article was reported.

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

Frontiers Media SA Acta Medica Okayama 2673-6616 6 2025 Maternal circulating GPIHBP1 levels and neonatal outcomes in patients with gestational diabetes mellitus: a pilot study 1682012 EN Mayu Watanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Jun Eguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Naoko Kurooka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Eriko Eto Department of Obstetrics and Gynecology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, 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 Introduction: The prevalence of gestational diabetes mellitus (GDM) is significantly increasing. Hyperglycaemia and dyslipidaemia have been demonstrated to contribute to endothelial dysfunction linked to foetal–placental circulation. Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) is crucial for the lipolytic processing of TG-rich lipoproteins through the anchoring of lipoprotein lipase (LPL). In this study, circulating GPIHBP1 levels during pregnancy were evaluated, and their associations with hypertriglyceridaemia and the perinatal outcomes of GDM were evaluated.<br> Methods: This study included 12 pregnant women with GDM and 21 pregnant women with normal glucose tolerance (NGT).<br> Results: No significant differences in obstetrical outcomes were detected between the two groups. In participants with NGT, circulating GPIHBP1 levels were markedly lower in the 3rd trimester than in the 2nd trimester and at delivery. In women with GDM, circulating GPIHBP1 levels were unchanged during the 3rd trimester, and circulating GPIHBP1 levels throughout the 3rd trimester were negatively correlated with neonatal birth weight percentile and umbilical venous pO2 (ρ=-0.636, p=0.026; ρ=-0.657, p=0.020).<br> Discussion: Our findings suggest a possible association between circulating GPIHBP1 levels and perinatal outcomes in patients with GDM. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1096-4959 281 2026 N-terminal domains and site-specific glycosylation regulate the secretion of avian melanocortin inverse agonists, agouti signaling protein (ASIP) and agouti-related protein (AGRP) 111174 EN Hibiki Fukuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ryoya Watanabe Graduate School of Natural Science and Technology, Okayama University Yuna Iida Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Saya Nakano Graduate School of Natural Science and Technology, Okayama University Aya Mizutani Graduate School of Natural Science and Technology, Okayama University Tatsuhiko Abo Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sayaka Aizawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sakae Takeuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Agouti signaling protein (ASIP) and agouti-related protein (AGRP) are paralogous inverse agonists of melanocortin receptors with distinct physiological roles, but their structural and biochemical properties in birds remain poorly understood. Here, we characterized chicken ASIP and AGRP proteins. Analysis of available sequences revealed that a motif resembling the mammalian proprotein convertase 1/3 (PC1/3, also known as PCSK1) cleavage site is conserved across a broad range of avian orders, but Western blot analysis of transfected Chinese hamster ovary (CHO-K1) cells and chicken hypothalamus detected no cleavage, suggesting that avian AGRP may not be post-translationally processed at this site. Chicken ASIP mRNA contains an in-frame upstream ATG (uATG) and a putative N-linked glycosylation site at Asn-42, both conserved across multiple avian orders. Overexpression in CHO-K1 cells showed that ASIP translated from either ATG produces a mature protein of the same size that is N-glycosylated at Asn-42 and exhibits markedly lower secretion efficiency than AGRP. Domain-swapping experiments revealed that the N-terminal domain reduces secretion, whereas a naturally occurring ASIP-b variant with an additional N-glycan at Asn-47 shows enhanced secretion. Proteasome inhibition increased intracellular ASIP, and endoglycosidase H (Endo H) sensitivity indicated endoplasmic reticulum (ER) retention, suggesting that the N-terminal domain limits secretion via ER-associated proteasomal degradation. These findings reveal species-specific post-translational regulation of avian melanocortin inverse agonists, in which N-terminal features and site-specific N-glycosylation determine secretion efficiency, likely contributing to their distinct roles in pigmentation and hypothalamic energy balance. No potential conflict of interest relevant to this article was reported.

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

Springer Nature Switzerland Acta Medica Okayama 0302-9743 2025 Effects of Visual Stimuli on Perceived Sound Volume in Virtual Reality Spaces 286 299 EN Yuki Matsuda Okayama University Toma Kobayashi Nara Institute of Science and Technology Hiroki Watanabe Future University Hakodate Keiichi Yasumoto Nara Institute of Science and Technology With the proliferation of affordable and high-performance virtual reality (VR) devices, VR content such as games and the metaverse is becoming increasingly widespread. In VR environments, users experience various sensory stimuli, primarily through visual and auditory cues. However, subjective perception of these stimuli varies based on user context. Existing studies have shown that auditory perception can be influenced by visual stimuli, however, most of them have focused on congruent audiovisual stimuli, leaving the effects of non-congruent pairings unexplored. This study investigates how visual stimuli, specifically color and crowdedness, influence perceived sound volume in VR. In the experiment that participants experienced VR environments with different room colors while listening to test tones, the results showed that warm colors led to higher perceived volume at low sound levels. Also, in the experiment that participants viewed VR scenes with varying crowd densities while hearing announcements, less crowded environments resulted in higher perceived sound volume. These findings suggest that visual context impacts auditory perception, providing insights for optimizing hearable devices and enhancing VR auditory experiences. No potential conflict of interest relevant to this article was reported.

Japanese Society of Microbial Ecology Acta Medica Okayama 1342-6311 40 3 2025 Role of Formate Chemoreceptor in Pseudomonas syringae pv. tabaci 6605 in Tobacco Infection ME25019 EN Phuoc Quy Thang Nguyen The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuta Watanabe The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hidenori Matsui The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nanami Sakata The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiteru Noutoshi The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuhiro Toyoda The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuki Ichinose The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Chemotaxis is essential for infection by plant pathogenic bacteria. The causal agent of tobacco wildfire disease, Pseudomonas syringae pv. tabaci 6605 (Pta6605), is known to cause severe leaf disease and is highly motile. The requirement of chemotaxis for infection has been demonstrated through the inoculation of mutant strains lacking chemotaxis sensory component proteins. Pta6605 possesses 54 genes that encode chemoreceptors (known as methyl-accepting chemotaxis proteins, MCPs). Chemoreceptors are classified into several groups based on the type and localization of ligand-binding domains (LBD). Cache LBD-type chemoreceptors have been reported to recognize formate in several bacterial species. In the present study, we identified Cache_3 Cache_2 LBD-type Mcp26 encoded by Pta6605_RS00335 as a chemoreceptor for formate using a quantitative capillary assay, and named it McpF. Although the deletion mutant of mcpF (ΔmcpF) retained attraction to 1% yeast extract, its chemotactic response to formate was markedly reduced. Swimming and swarming motilities were also impaired in the mutant. To investigate the effects of McpF on bacterial virulence, we conducted inoculations on tobacco plants using several methods. The ΔmcpF mutant exhibited weaker virulence in flood and spray assays than wild-type and complemented strains, highlighting not only the involvement of McpF in formate recognition, but also its critical role in leaf entry during the early stages of infection. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1752-1947 19 1 2025 The safety and efficacy of finasteride for transgender men with androgenetic alopecia: a case series 468 EN Yusuke Tominaga Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tomoko Kobayashi Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuko Matsumoto Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tomoko Sako Department of Urology, Hiroshima City Hiroshima Citizens Hospital Takatoshi Moriwake Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Satoshi Horii Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takuya Sadahira Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Satoshi Katayama Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takehiro Iwata Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shingo Nishimura Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kensuke Bekku Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kohei Edamura Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masami Watanabe Center for Innovative Clinical Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Motoo Araki Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Background Testosterone replacement therapy is commonly used in transgender men for masculinization. One of the most common adverse effects of testosterone replacement therapy is androgenetic alopecia. In Japan, finasteride is approved exclusively for cisgender men and is not indicated for transgender men. The aim of this clinical trial was to evaluate the safety and efficacy of finasteride in transgender men with androgenetic alopecia.<br> Case presentation This study included three transgender men (assigned female at birth, identifying as male), aged 44, 43, and 29 years. All participants were of Asian ethnicity. A clinical trial was conducted from October 2021 to December 2023. Transgender men aged 20–60 years who had not undergone hysterectomy, were undergoing testosterone replacement therapy, and who had been diagnosed with stage ≥ II androgenetic alopecia on the basis of the Norwood–Hamilton scale were recruited. The participants initiated treatment with 0.2 mg of finasteride per day for 3 months (phase 1). If no adverse events above grade 2 occurred, the dose was increased to 1.0 mg per day for an additional 3 months (phase 2). The primary endpoints were the incidence of treatment-related adverse events at 1 week, 1 month, and 3 months, as well as the rate of participants continuing treatment at 3 months. None of the patients experienced serious adverse events at 3 months, and all the patients extended their treatment to a total of 6 months. Improvements of at least one stage on the N–H scale were observed, but two participants experienced resumption of menstruation.<br> Conclusion Finasteride appears to be a safe and effective treatment for androgenetic alopecia in transgender men undergoing testosterone replacement therapy. However, its potential for reducing some of the effects of testosterone replacement therapy warrants further investigation. Trial registration: jRCT, jRCTs061210040, registered 7 October 2021, https://jrct.mhlw.go.jp/latest-detail/jRCTs061210040. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Epstein-Barr Virus-Associated Early Gastric Carcinoma with Lymphoid Stroma Mimicking a Submucosal Tumor: A Typical Case Diagnosed by Endoscopic Resection and Treated by Local Resection with Sentinel Node Navigation 399 404 EN Hiroshi Isozaki Department of Surgery, Oomoto Hospital Sasau Matsumoto Department of Surgery, Oomoto Hospital Takehiro Takama Department of Surgery, Oomoto Hospital Yuka Isozaki Department of Surgery, Oomoto Hospital Shigeki Murakami Department of Surgery, Oomoto Hospital Case Report 10.18926/AMO/69442 Gastric cancer with lymphoid stroma (GCLS) accounts for 1%-7% of gastric cancers; ~80% are Epstein-Barr virus (EBV)-positive. The rate of lymph node metastasis is relatively low, even when an early GCLS has invaded the submucosa. We report an early GCLS with massive submucosal invasion mimicking a submucosal tumor (SMT), diagnosed by endoscopic submucosal resection (ESD) and treated with local resection and sentinel node navigation surgery (SNNS). The patient was a 40-year-old Japanese man. A protruding lesion on the greater curvature of the middle part of his stomach was detected by X-ray, and an endoscopic examination revealed a 2.5-cm protruding tumor covered with a normal mucosa and small ulcers at the apex. ESD was performed for a diagnosis. The pathological diagnosis was lymphoepithelioma-like gastric cancer (GCLS), pT1b(SM2), Ly0, V0, pHM1, pVM1. EBV infection in the cancer cells was confirmed pathologically by EBV-encoded RNA. The local resection was performed using SNNS. The patient has had no recurrence or post-gastrectomy syndrome 4 years postsurgery. EBV-associated early GCLS resembling an SMT is relatively rare, and clinicians need to be aware of this disease. Local resection using SNNS may be a surgical option for GCLS cases with a low rate of lymphatic metastasis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Gastroduodenal Artery-Preserving Pancreatoduodenectomy after Esophagectomy with Gastric Conduit Reconstruction 393 398 EN Akari Masunaga 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 Yasuo Nagai 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 Motohiko Yamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeyoshi Nishiyama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriyuki Kanehira Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yumi Sota Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/69441 Pancreatoduodenectomy (PD) after esophagectomy with gastric conduit reconstruction is technically challenging. Preserving the blood supply of the gastric conduit is crucial in performing PD after esophagectomy. We report the case of a 66-year-old man who underwent gastroduodenal artery-preserving PD after esophagectomy with gastric conduit reconstruction for intraductal papillary mucinous neoplasm. The patient developed pseudoaneurysm rupture postoperatively, but was successfully treated with interventional radiology. Precise assessment is important in developing a surgical strategy depending on the patient’s specific anatomy and tumor characteristics. Moreover, special attention should be paid to avoid accidental injuries of the gastric conduit and gastric vessels during surgery. 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.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Inhibition of Air-Exposure Stress–Induced Autolysis in Clostridium perfringens by Zn2+ 345 352 EN Nozomu Matsunaga Department of Life Science, Faculty of Science, Okayama University of Science Seira Egusa Department of Life Science, Faculty of Science, Okayama University of Science Riyo Aono Department of Medical Technology, Kagawa Prefectural University of Health Sciences Eiji Tamai Department of Infectious Disease, College of Pharmaceutical Science, Matsuyama University Yasuo Hitusmoto Department of Life Science, Faculty of Science, Okayama University of Science Seiichi Katayama Department of Life Science, Faculty of Science, Okayama University of Science Original Article 10.18926/AMO/69435 Clostridium perfringens is a pathogenic anaerobe that causes gas gangrene and food poisoning. Although autolysin-mediated reorganization of the bacterial cell wall is crucial for cell division, excessive autolysin activity induced by stressors can lead to cell lysis. In C. perfringens, air exposure is a significant stressor that causes cell lysis, and Acp (N-acetylglucosaminidase) is known to be a major autolysin. To further facilitate C. perfringens research, a technology to prevent air-induced cell lysis must be developed. This study investigated the role of Acp in air-induced autolysis and explored potential inhibitors that would prevent cell lysis during experimental procedures. Morphological analyses confirmed that Acp functions as an autolysin in C. perfringens, as acpdeficient strains exhibited filamentous growth. The mutants exhibited negligible autolysis under air-exposure stress, confirming the involvement of Acp in the autolytic process. We also evaluated the effects of various divalent cations on Acp activity in vitro and identified Zn2+ as a potent inhibitor. Brief treatment with a Zn2+- containing buffer induced dose-dependent cell elongation and autolysis inhibition in C. perfringens. These findings demonstrate that simple Zn2+ treatment before experiments stabilizes C. perfringens cells, reducing autolysis under aerobic conditions and facilitating various biological studies, except morphological analyses. No potential conflict of interest relevant to this article was reported.

American Association for the Advancement of Science (AAAS) Acta Medica Okayama 2375-2548 11 38 2025 Polymeric microwave rectifiers enabled by monolayer-thick ionized donors eadv9952 EN Nobutaka Osakabe Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Jeongeun Her Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Takahiro Kaneta Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Akiko Tajima Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Elena Longhi School of Chemistry and Biochemistry and Center for Organic Photonics and Electronics, Georgia Institute of Technology Kan Tang Renewable and Sustainable Energy Institute, University of Colorado Boulder Kazuhiro Fujimori Faculty of Environmental, Life, Natural Science and Technology, Okayama University Stephen Barlow School of Chemistry and Biochemistry and Center for Organic Photonics and Electronics, Georgia Institute of Technology Seth R. Marder School of Chemistry and Biochemistry and Center for Organic Photonics and Electronics, Georgia Institute of Technology Shun Watanabe Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Jun Takeya Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Yu Yamashita Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Solution processing of polymeric semiconductors provides a facile way to fabricate functional diodes. However, energy barriers at metal-semiconductor interfaces often limit their performance. Here, we report rectifying polymer diodes with markedly modified energy-level alignments. The gold electrode surface was treated with a dimeric metal complex, which resulted in a shallow work function of 3.7 eV by forming a monolayer-thick ionized donor layer. When a polymeric semiconductor was coated on the treated electrode, most of the ionized donors remained at the metal-semiconductor interface. The confined ionized donors with the ideal thickness enabled fabrication of a polymer diode with a forward current density of over 100 A cm−2. Furthermore, a power conversion efficiency of 7.9% was observed for rectification at a microwave frequency of 920 MHz, which is orders of magnitude higher than that reported for organic diodes. Our findings will pave a way to solution-processed high-frequency and high-power devices. No potential conflict of interest relevant to this article was reported.

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

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

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

American Physiological Society Acta Medica Okayama 1040-0605 329 1 2025 Activated factor X inhibition ameliorates NF-κB-IL-6-mediated perivascular inflammation and pulmonary hypertension L183 L196 EN Satomi Imakiire Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Keiji Kimuro Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Keimei Yoshida Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Kohei Masaki Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Ryo Izumi Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Misaki Imabayashi Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Takanori Watanabe Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Tomohito Ishikawa Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Kazuya Hosokawa Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Shouji Matsushima Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Toru Hashimoto Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Keisuke Shinohara Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Shunsuke Katsuki Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Tetsuya Matoba Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Katsuya Hirano Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University Hiroyuki Tsutsui Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Kohtaro Abe Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Activated factor X (FXa) induces inflammatory response and cell proliferation in various cell types via activation of proteinase-activated receptor-1 (PAR1) and/or PAR2. We thus aimed to investigate the impact of FXa on the development of pulmonary arterial hypertension (PAH) and the mechanisms involved. The effects of edoxaban, a selective FXa inhibitor, on hemodynamic, right ventricular (RV) hypertrophy, and vascular remodeling were evaluated in a monocrotaline (MCT)-exposed pulmonary hypertension (PH) rat model. At 21 days after a single subcutaneous injection of MCT of 60 mg/kg, right ventricular systolic pressure (RVSP) and total pulmonary vascular resistance index (TPRI) were elevated concomitant with the increased plasma FXa and lung interleukin-6 (IL-6) mRNA. Daily administration of edoxaban (10 mg/kg/day, by gavage) starting from the day of MCT injection for 21 days ameliorated RVSP, TPRI, RV hypertrophy, pulmonary vascular remodeling, and macrophage accumulation. Edoxaban reduced nuclear factor-kappa B (NF-κB) activity and IL-6 mRNA level in the lungs of MCT-exposed rats. mRNA levels of FXa, PAR1, and PAR2 in cultured pulmonary arterial smooth muscle cells (PASMCs) isolated from patients with PAH were higher than those seen in normal PASMCs. FXa stimulation increased cell proliferation and mRNA level of IL-6 in normal PASMCs, both of which were blunted by edoxaban and PAR1 antagonist. Moreover, FXa stimulation activated extracellularly regulated kinases 1/2 in a PAR1-dependent manner. Inhibition of FXa ameliorates NF-κB-IL-6-mediated perivascular inflammation, pulmonary vascular remodeling, and the development of PH in MCT-exposed rats, suggesting that FXa may be a potential target for the treatment of PAH.<br> NEW & NOTEWORTHY This study demonstrated that chronic treatment with activated factor X (FXa) inhibitor ameliorated NF-κB-IL-6-mediated perivascular inflammation in a rat model with pulmonary arterial hypertension, which is associated with elevated FXa activity. FXa may act on pulmonary arterial smooth muscle cells, inducing cell proliferation and inflammatory response via upregulated PAR1, thereby contributing to pulmonary vascular remodeling. Understanding the patient-specific pathophysiology is a prerequisite for applying FXa-targeted therapy to the treatment of pulmonary arterial hypertension. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0007-0920 2025 Primary tumour resection plus systemic therapy versus systemic therapy alone in metastatic breast cancer (JCOG1017, PRIM-BC): a randomised clinical trial EN Tadahiko Shien Okayama University Hospital Fumikata Hara Cancer Institute Hospital Kenjiro Aogi National Hospital Organization Shikoku Cancer Center Yasuhiro Yanagida Shizuoka General Hospital Michiko Tsuneizumi Gunma Prefectural Cancer Center Naohito Yamamoto Chiba Prefectural Cancer Center Hiroshi Matsumoto Saitama Prefectural Cancer Center Akihiko Suto National Cancer Center Hospital Kenichi Watanabe Hokkaido Cancer Center Michiko Harao Jichi Medical University Hospital Chizuko Kanbayashi Niigata Prefectural Cancer Center Mitsuya Itoh Hiroshima City Hiroshima Citizen’s Hospital Takayuki Kadoya Hiroshima University Hospital Keisei Anan Kitakyushu Municipal Medical Center Shigeto Maeda Nagasaki Municipal Medical Center Keita Sasaki National Cancer Center Hospital Gakuto Ogawa National Cancer Center Hospital Shigehira Saji Fukushima Medical University Haruhiko Fukuda National Cancer Center Hospital Hiroji Iwata Aichi Cancer Center Hospital Background: Several prospective studies have evaluated the benefit of primary tumour resection (PTR) in de novo Stage IV breast cancer (BC) patients, but it remains controversial. We aimed to investigate whether PTR improves the survival of de novo stage IV BC patients.<br> Methods: De novo stage IV BC patients were enrolled in the first registration and received systemic therapies according to clinical subtypes. Patients without progression after primary systemic therapy for 3 months were randomly assigned 1:1 to systemic therapy alone (arm A) or PTR plus systemic therapy (arm B). The primary endpoint was overall survival (OS), and the secondary endpoints included local relapse-free survival (LRFS).<br> Results: Five hundred seventy patients were enrolled between May 5, 2011, and May 31, 2018. Of these, 407 were randomised to arm A (N = 205) or arm B (N = 202). The median follow-up time of all randomised patients was 60 months. The difference in OS was not statistically significant (HR 0.86 90% CI 0.69–1.07, one-sided p = 0.13). Median OS was 69 months (arm A) and 75 months (arm B). In the subgroup analysis, PTR was associated with improved OS in pre-menopausal patients, or those with single-organ metastasis. LRFS in arm B was significantly longer than that in arm A (median LRFS 20 vs. 63 months: HR 0.42, 95% CI 0.33–0.53, p < 0.0001). There were no treatment-related deaths.<br> Conclusions: PTR did not prolong OS. However, it improved local control and might benefit a subset of patients, such as those with premenopausal status or with single-organ metastasis. It also improved local relapse-free survival (LRFS), which is a clinically meaningful outcome in trials of systemic therapy.<br> Clinical trial registration: UMIN Clinical Trials Registry (UMIN000005586); Japan Registry of Clinical Trials (jRCTs031180151). No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2691-3704 5 2 2025 Mechanistic Insights Into Oxidative Response of Heat Shock Factor 1 Condensates 606 617 EN Soichiro Kawagoe Institute of Advanced Medical Sciences, Tokushima University Motonori Matsusaki Institute of Advanced Medical Sciences, Tokushima University Takuya Mabuchi Frontier Research Institute for Interdisciplinary Sciences, Tohoku University Yuto Ogasawara Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kazunori Watanabe Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Koichiro Ishimori Department of Chemistry, Faculty of Science, Hokkaido University Tomohide Saio Institute of Advanced Medical Sciences, Tokushima University Heat shock factor 1 (Hsf1), a hub protein in the stress response and cell fate decisions, senses the strength, type, and duration of stress to balance cell survival and death through an unknown mechanism. Recently, changes in the physical property of Hsf1 condensates due to persistent stress have been suggested to trigger apoptosis, highlighting the importance of biological phase separation and transition in cell fate decisions. In this study, the mechanism underlying Hsf1 droplet formation and oxidative response was investigated through 3D refractive index imaging of the internal architecture, corroborated by molecular dynamics simulations and biophysical/biochemical experiments. We found that, in response to oxidative conditions, Hsf1 formed liquid condensates that suppressed its internal mobility. Furthermore, these conditions triggered the hyper-oligomerization of Hsf1, mediated by disulfide bonds and secondary structure stabilization, leading to the formation of dense core particles in the Hsf1 droplet. Collectively, these data demonstrate how the physical property of Hsf1 condensates undergoes an oxidative transition by sensing redox conditions to potentially drive cell fate decisions. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 Outcome of Decompression Surgery Following Rapid Neurological Deterioration in Patients with Spinal Cord Injury Without Radiographic Evidence of Trauma (SCIWORET) 261 267 EN Yuichi Hirata Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiaki Sugahara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Sasada Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hayato Miyake Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Nagase Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takao Yasuhara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/69151 Cervical spondylotic myelopathy (CSM) and ossification of the posterior longitudinal ligament (OPLL) increase the likelihood of spinal cord injury without radiographic evidence of trauma (SCIWORET). Opinions regarding the optimal timing for surgery in such cases vary, however. We retrospectively investigated the demographics and outcomes of patients with SCIWORET who underwent surgery shortly after experiencing rapid neurological deterioration, and we matched patients who underwent standby surgery for CSM or OPLL. Although the optimal timing of surgery for SCIWORET remains unclear, our findings suggest that early stage surgery for SCIWORET may yield favorable neurological improvements. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 A Study of Periprosthetic Femoral Stem Fractures in Hip Arthroplasty for Femoral Neck Fracture 253 259 EN Yoshiaki Miyake Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Toru Takagi Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Taizo Konishiike Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Original Article 10.18926/AMO/69150 This study investigated the risk factors for bone fragility and perioperative periprosthetic femoral stem fractures in patients undergoing hip arthroplasty for femoral neck fractures. The records of 215 patients (42 male, 173 female; mean age, 84.4 years) were analyzed to assess correlations among periprosthetic fracture rates and sex, age, body mass index (BMI), Dorr classification, femoral stem fixation type (cemented/cementless), and bone mineral density (BMD) of the contralateral proximal femur. The overall prevalence of perioperative periprosthetic fractures was 4.7%. All patients with periprosthetic fractures were female, and all but one were ≥ 80 years of age. Fracture rates were higher in patients with lower BMI, although this difference was not significant. The fracture rates were 0%, 4.7%, and 7.9% for Dorr types A, B, and C, respectively, and 0% and 5.3% for patients who received cemented and cementless stems, respectively. The findings indicated that female patients, those of advanced age, those with lower BMI, and those with Dorr type C had lower BMDs. Although BMD was significantly lower in patients who received cemented stems compared to those who received cementless stems, no fractures were observed in the former group, suggesting that the use of cemented stems is safe for this high-risk population. No potential conflict of interest relevant to this article was reported.

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

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

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

Elsevier BV Acta Medica Okayama 0003-4975 120 1 2025 Comparable Clinical Outcomes Between Segmentectomy and Lobectomy for NSCLC With Unsuspected N1/N2: A Multicenter Real-World Data Study 87 98 EN Tsuyoshi Ryuko 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 Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Ken Suzawa 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 Tsuyoshi Ueno Okayama University Thoracic Surgery Study Group Toshiya Fujiwara Okayama University Thoracic Surgery Study Group Mototsugu Watanabe Okayama University Thoracic Surgery Study Group Hidetoshi Inokawa Okayama University Thoracic Surgery Study Group Takahiko Misao Okayama University Thoracic Surgery Study Group Hidejiro Torigoe Okayama University Thoracic Surgery Study Group Kazuhiro Washio Okayama University Thoracic Surgery Study Group Hiroyuki Tao Okayama University Thoracic Surgery Study Group Daisuke Okutani Okayama University Thoracic Surgery Study Group Makio Hayama Okayama University Thoracic Surgery Study Group Masashi Uomoto Okayama University Thoracic Surgery Study Group Eiji Yamada Okayama University Thoracic Surgery Study Group Shinji Otani Okayama University Thoracic Surgery Study Group Takeshi Kurosaki Okayama University Thoracic Surgery Study Group Yuji Yaginuma Okayama University Thoracic Surgery Study Group Eito Niman Okayama University Thoracic Surgery Study Group Osamu Kawamata Okayama University Thoracic Surgery Study Group Hitoshi Nishikawa Okayama University Thoracic Surgery Study Group Tomoaki Otsuka Okayama University Thoracic Surgery Study Group Takeshi Yoshikawa Okayama University Thoracic Surgery Study Group Tatsuro Hayashi Okayama University Thoracic Surgery Study Group Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Segmentectomy for lung cancer has been increasingly performed. However, evidence regarding the necessity of additional surgical resection after the diagnosis of unsuspected N1 or N2 lymph node metastasis is limited.<br> Methods We conducted a multicenter, real-world data study of patients with any clinical T and N0 non-small cell lung cancer (NSCLC) who underwent lobectomy or segmentectomy between 2012 and 2021 and who subsequently received a diagnosis of pathologic N1 or N2 lymph node metastasis. Patients were categorized into lobectomy and segmentectomy groups. We analyzed overall survival (OS), recurrence-free survival (RFS), cumulative recurrence rates, and recurrence patterns using both unadjusted and propensity score–adjusted cohorts.<br> Results A total of 736 patients were in the lobectomy group, and 70 were in the segmentectomy group. In the unadjusted cohort, segmentectomy-treated patients were older, had a lower preoperative percentage of vital capacity, had smaller tumors, and received less postoperative adjuvant chemotherapy. The 5-year OS was significantly worse in the segmentectomy group (P = .011), with no significant differences in 5-year RFS or cumulative recurrence rates. In the propensity score–adjusted cohort, there were no significant differences in OS, RFS, or recurrence rates; however, the segmentectomy group had a higher rate of local recurrence.<br> Conclusions In patients with unsuspected N1 or N2 NSCLC, analysis using a cohort adjusted for patient background with propensity scores revealed no differences in OS, RFS, or cumulative recurrence rates between segmentectomy and lobectomy. This finding suggests that additional resection of the remaining segments may not be necessary for these patients. However, the higher rate of local recurrence in the segmentectomy group warrants careful consideration. No potential conflict of interest relevant to this article was reported.

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

American Chemical Society (ACS) Acta Medica Okayama 2637-6105 2025 Tailoring Mechanical Properties and Ionic Conductivity of Poly(ionic liquid)-Based Ion Gels by Tuning Anion Compositions EN Takaichi Watanabe Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Yuna Mizutani Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Carlos G. Lopez Material Science and Engineering Department, The Pennsylvania State University, 80 Pollock Road, State College Tsutomu Ono Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Poly(ionic liquid) (PIL)-based ion gels have emerged as promising materials for advanced electrochemical applications because of their excellent miscibility with ionic liquids (IL), tunable mechanical properties, and high ionic conductivity. Despite extensive studies on PIL-based ion gels, a comprehensive understanding of how different anion combinations in the system affect physicochemical properties is lacking. In this study, we systematically investigate the effect of different anion species, such as bis(trifluoromethanesulfonyl)imide (TFSI) and hexafluorophosphate (PF6), on the mechanical, viscoelastic, and ion conductive behaviors of PIL-based ion gels. We investigate the interplay between anion size, packing density, and polymer segmental dynamics by varying the anion composition in both the PIL network and IL component. Rheological analysis and uniaxial tensile testing results indicate that PF6-containing ion gels exhibit enhanced higher Young’s modulus because of their restricted chain mobility resulting in higher glass transition temperature (Tg). In addition, we confirm the anion exchange between PIL and IL during gel preparation and find that the mechanical and ion conductive properties of the gels are governed by the total molar ratio of anions in the gels. Our findings highlight that tuning the anion composition in PIL-based ion gels provides an effective strategy to tailor their performance, with potential applications for flexible electronics and solid-state electrochemical devices. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2642-4150 2025 Electrostatically‐Driven Collapse of Polyelectrolytes: The Role of the Solvent's Dielectric Constant EN Anish Gulati Institute of Physical Chemistry, RWTH Aachen University Lingzi Meng Materials Science and Engineering Department, The Pennsylvania State University, State College Takaichi Watanabe Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Carlos G. Lopez Materials Science and Engineering Department, The Pennsylvania State University, State College We experimentally confirm a longstanding theoretical prediction of counterion-induced polyelectrolyte collapse in low dielectric media. The scattering behavior of polystyrene sulfonate in different solvents with dielectric permittivities in the range of ε ≃ 12 − 180 is investigated. For high and intermediate ε media, typical polyelectrolyte behavior is observed: the correlation length (ξ) scales with concentration (c) as ξ ∼ c−1∕2, as predicted by various theories. When the dielectric constant of the solvent decreases below ≃ 22, a scaling of ξ ∼ c−1∕3, characteristic of partially collapsed polyelectrolytes, is observed. For these solvents, the correlation peak disappears at high concentrations. Interestingly, polyelectrolyte collapse is observed under both solvophilic and solvophobic conditions, supporting the existence of attractive electrostatic interactions. These results are in qualitative agreement with theoretical predictions which expect chain collapse in low dielectric media due to the influence of condensed counterions, either via dipolar attraction and/or charge-correlation-induced attractions. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Survival days of patients with metastatic spinal tumors of lung cancer requiring surgery: a prospective multicenter study 24117 EN Takuya Takahashi Department of Orthopedic Surgery, Institute of Science Tokyo Takashi Hirai Department of Orthopedic Surgery, Institute of Science Tokyo Yuki Shiratani Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University Akinobu Suzuki Department of Orthopaedic Surgery, Osaka Metropolitan University Kenichiro Kakutani Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine Satoshi Kato Department of Orthopaedic Surgery Graduate School of Medical Sciences, Kanazawa University Hiroyuki Tominaga Department of Orthopedic Surgery Graduate School of Medical and Dental Sciences, Kagoshima University Hirokazu Inoue Rehabilitation Center, Jichi Medical University Hospital Hirokatsu Sawada Department of Orthopaedic Surgery, Nihon University School of Medicine Norihiko Takegami Department of Orthopaedic Surgery, Mie University Graduate School of Medicine Kazuo Nakanishi Department of Orthopaedic Surgery, Kawasaki Medical School Hideaki Nakajima Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui Masayuki Ishihara Department of Orthopaedic surgery, Kansai Medical University Hospital Tsutomu Oshigiri Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine Toru Funayama Department of Orthopaedic Surgery Institute of Medicine, University of Tsukuba Takuya Iimura Department of Orthopaedic Surgery, Dokkyo Medical University Shinji Tanishima Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University Hiroaki Nakashima Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Daisuke Yamabe Department of Orthopaedic Surgery, Iwate Medical University Ko Hashimoto Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine Koji Uotani Department of Orthopaedic Surgery, Okayama University Hospital Masahiro Funaba Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine Narihito Nagoshi Department of Orthopaedic Surgery, Keio University Kazu Kobayakawa Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University Toshitaka Yoshii Department of Orthopedic Surgery, Institute of Science Tokyo Kazuyuki Watanabe Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine Toshio Nakamae Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Takashi Kaito Department of Orthopedic Surgery, Osaka University Graduate School of Medicine Gen Inoue Department of Orthopaedic Surgery, Kitasato University School of Medicine Shiro Imagama Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Kota Watanabe Department of Orthopaedic Surgery, Keio University Takeo Furuya Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University Surgery for metastatic spinal tumors has improved postoperative activities of daily living. A few studies reported on prognostic factors assessed in large multicenter prospective studies for metastatic spinal tumors of lung cancer origin. This study aimed to determine preoperative prognostic factors in patients undergoing surgery for metastatic spinal tumors associated with lung cancer. This prospective registry study included 74 patients diagnosed and operated with metastatic spine tumors derived from lung cancer in 39 high-volume cancer centers. We examined the postoperative survival period and the preoperative factors related to postoperative survival time. We conducted univariate and multivariate Cox regression analyses to determine preoperative prognostic factors. The mean postoperative survival period was 343 days. Multivariate Cox regression analysis revealed a higher feeding score of vitality index, indications for molecularly targeted therapy, and a higher mobility score of Barthel index as independent factors associated with postoperative survival time in metastatic spinal tumors derived from lung cancer. Patients with indications for molecular-targeted therapy and good vitality exhibited longer survival. These results may help in surgical selection for patients with metastatic spinal tumors derived from lung cancer. No potential conflict of interest relevant to this article was reported.

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

MDPI AG Acta Medica Okayama 2076-2615 15 10 2025 A Canine c-kit Novel Mutation Isolated from a Gastrointestinal Stromal Tumor (GIST) Retains the Ability to Form Dimers but Lacks Autophosphorylation 1444 EN Kei Shimakawa Laboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science University So Doge Laboratory of Veterinary Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University Masaki Michishita Laboratory of Veterinary Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University Eri Tanabe Laboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science University Tsuyoshi Tajima Laboratory of Veterinary Pharmacology, School of Veterinary Science, Nippon Veterinary and Life Science University Masato Kobayashi Laboratory of Veterinary Reproduction, School of Veterinary Science, Nippon Veterinary and Life Science University Makoto Bonkobara Laboratory of Veterinary Clinical Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University Masami Watanabe Laboratory of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiko Ochiai Laboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science University Yoshikazu Tanaka Laboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science University Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that develop in the gastrointestinal tract; KIT mutations are present in both canine and human GISTs. In this study, genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) sections of 55 canine GIST cases, and mutation searches were performed for exons 8, 9, and 11. The results revealed novel mutations, A434T and F436S, in exon 8. In contrast to the A434T mutation without functional changes, the F436S mutant retained its dimerization ability, but lost its phosphorylation function and attenuated downstream Akt signaling, which is reflected in wound healing and migration activities. A comparison of the subcellular localization of WT KIT and the F436S mutant revealed no differences. In silico simulations indicated that the F436S mutation alters the structure of the near-membrane region and that its effects may extend to the transmembrane and intracellular domains compared to the WT. F436S is a point mutation that affects the entire molecule because co-mutation with the F436S mutation and the known autophosphorylation mutation reduces the autophosphorylation abilities. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0969-8051 144-145 2025 Investigating the fate of Zirconium-89 labelled antibody in cynomolgus macaques 109001 EN Takanori Sasaki Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Sadaaki Kimura Astellas Pharma Inc. Akihiro Noda Astellas Pharma Inc. Yoshihiro Murakami Astellas Pharma Inc. Sosuke Miyoshi Astellas Pharma Inc. Masaru Akehi Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kazuhiko Ochiai School of Veterinary Nursing and Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University Masami Watanabe Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takahiro Higuchi Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Eiji Matsuura Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background: Preclinical pharmacokinetic studies of therapeutic antibodies in non-human primates are desired because of the difficulty in extrapolating ADME data from animal models to humans. We evaluated the pharmacokinetics of 89Zr (Zirconium-89) -labelled anti-KLH human IgG and its metabolites to confirm their non-specific/physiological accumulation in healthy cynomolgus macaques. The anti-KLH antibody was used as a negative control, ensuring that the observed distribution reflected general IgG behavior rather than antigen-specific accumulation. This provides a valuable reference for comparing the biodistribution of targeted antibodies.<br> Methods: Selected IgG was conjugated to desferrioxamine (DFO), labelled with 89Zr, and injected into healthy cynomolgus macaques. PET/CT images at the whole-body level were acquired at different time points, and standard uptake values (SUV) in regions of interest, such as the heart, liver, spleen, kidneys, bone, and muscles, were calculated. The distribution of a shortened antibody variant, 89Zr-labelled Fab, as well as that of [89Zr]Zr-DFO and [89Zr]Zr-oxalate, the expected metabolites of 89Zr- labelled IgG, was also assessed.<br> Results: After 89Zr-labelled IgG injection, the SUV in the heart, vertebral body, and muscle decreased, in line with the 89Zr concentration decrease in the circulation, whereas radioactivity increased over time in the kidneys and liver. Autoradiography of the renal sections indicated that most of the 89Zr- labelled IgG radioactivity accumulated in the renal cortex. Relatively high accumulation in the kidneys was also observed in 89Zr- labelled Fab-injected macaques, and renal autoradiographs of these animals showed that the renal cortex was the preferred accumulation site. However, [89Zr]Zr-DFO was rapidly excreted into the urine, whereas [89Zr]Zr-oxalate was highly accumulated in the epiphysis of the long bones and vertebral body.<br> Conclusion: In the non-human primate cynomolgus macaque, 89Zr- labelled IgG accumulated in the kidneys and the liver. However, [89Zr]Zr-DFO and 89Zr did not accumulate in these organs. This preclinical pharmacokinetic study performed with human IgG in a non-human primate model using PET is of great significance as it sheds light on the basic fate and distribution of 89Zr- labelled IgG. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2468-0249 10 6 2025 Dotinurad Treatment for Patients With Hyperuricemia Complicating CKD 1711 1720 EN Katsuyuki Tanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Nunoue Nunoue Clinic Naoki Itabashi Itabashi Diabetes and Dermatology Medical Clinic Akihiro Katayama NHO Okayama Medical Center Akihiko Nakamura Osafune Clinic Hiroyuki Ohbayashi Tohno Chuo Clinic Yasuhiro Onishi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kyoko Watanabe Japanese Red Cross Okayama Hospital Keisuke Maruyama Okayama Saiseikai Outpatient Center Hospital Takeshi Hosoya Hosoya Clinic Shinichi Okada Okada Medical Clinic Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Introduction: The management of hyperuricemia is important to reduce cardiovascular risk and the progression of renal injury in chronic kidney disease (CKD). This study aimed to assess the efficacy and safety of dotinurad, a novel urate transporter-1 inhibitor, in patients with hyperuricemia and CKD.<br> Methods: In a nonrandomized, parallel interventional study, patients were grouped based on their estimated glomerular filtration rate (eGFR) at baseline. The starting dotinurad dose was 0.5 mg/d and titrated to a final dose of 2 mg/d to 4 mg/d. The primary end point was the noninferiority of the change in serum uric acid (UA) levels between the G1/G2 and G3/G4 groups at week 24. The main secondary end points were changes in eGFR and UA clearance-to-creatinine clearance ratio (CUA/CCr). Reported adverse events were also investigated.<br> Results: Ninety-eight patients continued the dose titration. The mean percentage reduction in serum UA level at week 24 were 47.2% and 42.8% for the G1/G2 and G3/G4 groups, respectively; the between-group difference was −4.3% (95% confidence interval [CI], −9.5% to 0.9%, noninferiority P = 0.0321), validating the noninferiority of treatment in the G3/G4 group to the G1/G2 group. eGFR tended to increase slightly through to week 24, suggesting that spontaneous eGFR decline was counteracted. Mean CUA/CCr generally increased over time from week 4 to week 24. No new safety issues of particular concern were identified; and there were no marked changes in urinary pH.<br> Conclusion: Dotinurad therapy may be well-tolerated in patients with hyperuricemia and may have efficacy comparable with existing standard treatment in patients with CKD stages G3/G4. Randomized controlled trials in larger patient groups are needed. 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 2772-4174 13 2025 Photochemical internalization of mRNA using a photosensitizer and nucleic acid carriers 100242 EN Hayaki Maemoto Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ryohei Suzaki Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kazunori Watanabe Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Keiji Itaka Department of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University Takashi Ohtsuki Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University mRNA has great potential for therapeutic applications because it can encode a variety of proteins and antigens, in addition to advantages over DNA in terms of gene expression without genomic integration, nuclear localization, or transcription. However, therapeutic applications of mRNA require safe and effective delivery into target cells. Therefore, we aimed to investigate photochemical internalization (PCI) as a promising strategy for delivering mRNA to target cells. In this strategy, mRNA is taken up into cells by endocytosis, accumulates in endosomes, and is released in a light-dependent manner from the endosomes using an endosome-accumulating photosensitizer, aluminum phthalocyanine disulfonate (AlPcS2a), in combination with nucleic acid carrier molecules. We compared the efficacy of various nucleic acid carriers, including branched polyethyleneimine (bPEI) and poly{N'-[N-(2-aminoethyl)-2-aminoethyl] aspartamide} (PAsp(DET)) under the same conditions for PCI-based mRNA delivery. Our results indicated that bPEI and PAsp(DET) at low N/P ratios exhibited efficient light-enhancement of mRNA expression by PCI with AlPcS2a. Notably, bPEI exhibited the highest light-dependent mRNA delivery among the carriers evaluated (including cationic polymers, cationic peptides, and lipids), whereas PAsp(DET) showed promise for clinical use because of its lower toxicity compared with bPEI. This PCI strategy allows effective cytosolic mRNA delivery at low N/P ratios, thereby reducing cationic carrier molecule-induced cytotoxicity. This method allows spatiotemporal control of protein expression and holds potential for novel light-dependent mRNA therapies. Overall, this study provided valuable insights into optimizing mRNA delivery systems for therapeutic applications. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Role of galectin-9 in the development of gestational diabetes mellitus 18981 EN Haya Hamed Hassan Albuayjan Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mayu Watanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryosuke Sugawara Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eri Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koki Mise Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yukiko Oi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ayaka Kanno Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University BoXuan Yang Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshihisa Tahara Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ichiro Nojima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsuko Nakatsuka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Eguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jota Maki Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eriko Eto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kei Hayata Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Galectin-9 (Gal-9) is highly expressed in trophoblasts in placenta. Interaction between Gal-9 and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) is important for the differentiation of tissue resident natural killer (trNK) cells in placenta and maintenance of normal pregnancy. Furthermore, the enhanced maternal systemic inflammation associated with increased proinflammatory cytokines in preeclampsia is mediated by enhanced interaction between Gal-9 and Tim-3. However, the role of Gal-9 in gestational diabetes (GDM) remains unexplored. Plasma Gal-9 levels were elevated at 3rd trimester in pregnant women with GDM and positively correlated with placenta and newborn weight. Lgals9 knockout pregnant mice fed with high fat diet (HFD KO) demonstrated maternal glucose intolerance and fetus macrosomia compared with controls (HFD WT). In HFD KO, increased proliferating cells, reduced apoptosis, and autophagy impairment were observed in junctional zones. The number of trNK cells and percentage of Tim-3 + trNK increased, while early apoptosis percentage in Tim-3 + trNK was reduced in placenta of HFD KO. The elevation of plasma Gal-9 may be a biomarker for prediction of maternal glucose intolerance and fetal macrosomia in pregnant women with GDM and Gal-9 functions as a compensation factor for GDM by inducing apoptosis in Tim-3 + trNK cells. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Activated CTLA-4-independent immunosuppression of Treg cells disturbs CTLA-4 blockade-mediated antitumor immunity EN Tomofumi WATANABE Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 3 2025 A Case of Chromophobe Renal Cell Carcinoma Metastasizing to the Cervical Lymph Nodes after Long-term Follow-up 213 219 EN Makoto Watanabe Department of Otolaryngology, Chugoku Rosai Hospital Tomoyuki Ogawa Department of Otolaryngology, Chugoku Rosai Hospital Kanao Kobayashi Department of Nephrology and Urological Surgery, Chugoku Rosai Hospital Narutaka Katsuya Department of Molecular Pathology, Graduate School of Medical Sciences, Hiroshima University Akira Ishikawa Department of Molecular Pathology, Graduate School of Medical Sciences, Hiroshima University Takao Hamamoto Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital Hiroaki Tahara Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital Tsutomu Ueda Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital Sachio Takeno Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital Case Report 10.18926/AMO/68730 Renal cell carcinoma (RCC) can metastasize hematogenously and recur after a long dormancy. Chromophobe RCC metastasized to the cervical lymph nodes 10 years after the primary resection in a woman who underwent nephrectomy for RCC (T1aN0M0 stage I). Metastatic RCC diagnosis was confirmed by aspiration. The lymph node mass was resected, and the tumor cells matched chromophobe RCC metastasis. No adjuvant therapy was administered due to the lack of evidence regarding adjuvant therapy for chromophobe RCC. Long-term surveillance is crucial in RCC because of the possibility of late metastasis. We reviewed the clinical aspects and literature on metastatic cervical RCC. No potential conflict of interest relevant to this article was reported.

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

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

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

Okayama University Medical School Acta Medica Okayama 0386-300X 79 3 2025 Immunometabolic Regulation of Innate Immunity in Systemic Lupus Erythematosus 147 155 EN Haruki Watanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Matsumoto 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 Review 10.18926/AMO/68722 Pathogens or their components can induce long-lasting changes in the behavior of innate immune cells, a process analogous to “training” for future threats or environmental adaptation. However, such training can sometimes have unintended consequences, such as the development of autoimmunity. Systemic lupus erythematosus (SLE) is a chronic and heterogeneous autoimmune disease characterized by the production of autoantibodies and progressive organ damage. Innate immunity plays a central role in its pathogenesis, contributing through impaired clearance of apoptotic cells, excessive type I interferon production, and dysregulated formation of neutrophil extracellular traps. Recent studies have revealed that metabolites and nucleic acids derived from mitochondria, a crucial energy production site, directly regulate type I interferon and anti-inflammatory cytokine production. These insights have fueled interest in targeting metabolic pathways as a novel therapeutic approach for SLE, offering promise for improving long-term patient outcomes. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1464-6722 26 5 2025 Genomic Islands of Pseudomonas syringae pv. tabaci 6605: Identification of PtaGI-1 as a Pathogenicity Island With Effector Genes and a Tabtoxin Cluster e70087 EN Yuta Watanabe The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kotomi Kunishi Faculty of Agriculture,Okayama University Hidenori Matsui The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nanami Sakata The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiteru Noutoshi The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuhiro Toyoda The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuki Ichinose The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Genomic islands (GIs) are 20-500 kb DNA regions that are thought to be acquired by horizontal gene transfer. GIs that confer pathogenicity and environmental adaptation have been reported in Pseudomonas species; however, GIs that enhance bacterial virulence have not. Here, we identified 110 kb and 103 kb GIs in P. syringae pv. tabaci 6605 (Pta6605), the causative agent of tobacco wildfire disease, which has the ability to produce tabtoxin as a phytotoxin. These GIs are partially homologous to known genomic islands in Pseudomonas aeruginosa and P. syringae pv. phaseolicola and were designated PtaGI-1 and PtaGI-2. Both PtaGIs conserve core genes, whereas each GI possesses different accessory genes. PtaGI-1 contains a tabtoxin biosynthetic gene cluster and three type III effector genes among its accessory genes, whereas PtaGI-2 also contains homologous genes to hsvABC, pathogenicity-related genes in Erwinia amylovora. Inoculation revealed that the PtaGI-1 mutant, but not the PtaGI-2 mutant, lost the ability to biosynthesise tabtoxin and to cause disease. Therefore, PtaGI-1 is thought to be a pathogenicity island. Both PtaGI-1 and PtaGI-2 have a pseudogene of tRNALys on the left border and an intact tRNALys gene on the right border. In a colony of Pta6605, both GIs can be excised at tRNALys, and PtaGI-1 and PtaGI-2 exist in a circular form. These results indicate that tabtoxin biosynthesis genes in PtaGI-1 are required for disease development, and PtaGI-1 is necessary for Pta6605 virulence. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2470-1343 2025 High-Resolution HPLC for Separating Peptide-Oligonucleotide Conjugates EN Miyako Naganuma Division of Organic Chemistry, National Institute of Health Sciences Genichiro Tsuji Division of Organic Chemistry, National Institute of Health Sciences Misato Amiya YMC CO., LTD. Reira Hirai YMC CO., LTD. Yuki Higuchi YMC CO., LTD. Naoko Hata YMC CO., LTD. Saoko Nozawa YMC CO., LTD. Daishi Watanabe Division of Organic Chemistry, National Institute of Health Sciences Taeko Nakajima YMC CO., LTD. Yosuke Demizu Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Division of Pharmaceutical Science, Okayama University Peptide-oligonucleotide conjugates (POCs) are chimeric molecules that combine the specificity of oligonucleotides with the functionality of peptides, improving the delivery and therapeutic potential of nucleic acid-based drugs. However, the analysis of POCs, particularly those containing arginine-rich sequences, poses major challenges because of aggregation caused by electrostatic interactions. In this study, we developed an optimized high-performance liquid chromatography (HPLC) method for analyzing POCs. Using a conjugate of DNA and nona-arginine as a model compound, we systematically investigated the effects of various analytical parameters, including column type, column temperature, mobile-phase composition, and pH. A column packed with C18 resin with wide pores combined with butylammonium acetate as the ion-pairing reagent and an optimal column temperature of 80 degrees C provided superior peak resolution and sensitivity. The optimized conditions gave clear separation of POCs from unlinked oligonucleotides and enabled the detection of nucleic acid fragments lacking an alkyne moiety as a linkage part, which is critical for quality control. Our HPLC method is robust and reproducible and substantially reduces the complexity, time, and cost associated with the POC analysis. The method may improve the efficiency of quality control in the production of POCs, thereby supporting their development as promising therapeutic agents for clinical applications. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 137 1 2025 泌尿器科領域におけるロボット手術の進化と未来 25 29 EN Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoya Nagasaki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Okamoto Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Shiraishi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aya Taira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shota Inoue Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuya Kawago Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomofumi Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masao Mitsui Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Horii Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takatoshi Moriwake Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kasumi Yoshinaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Mitsui Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoaki Yamanoi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsushi Kawada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Tominaga 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 Satoshi Katayama 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 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 Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 2 2025 Safe Resection of Esophageal Cancer with a Non-Recurrent Inferior Laryngeal Nerve Associated with an Aberrant Right Subclavian Artery Using Intraoperative Nerve Monitoring 139 144 EN Yasushige Takeda Department of Gastroenterological Surgery, Okayama University Hospital Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Hospital Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Hospital Yohei Mizusawa Department of Gastroenterological Surgery, Okayama University Hospital Hijiri Matsumoto Department of Gastroenterological Surgery, Okayama University Hospital Yuhei Kondo Department of Gastroenterological Surgery, Okayama University Hospital Tomoyoshi Kunitomo Department of Gastroenterological Surgery, Okayama University Hospital Yukinori Tanoue Department of Gastroenterological Surgery, Okayama University Hospital Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Hospital Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Hospital Case Report 10.18926/AMO/68654 In thoracic esophageal cancer, lymph node dissection around the recurrent laryngeal nerve is crucial but poses a risk of nerve palsy, affecting postoperative quality of life. In cases with an aberrant right subclavian artery (ARSA), the right recurrent laryngeal nerve is absent, and the non-recurrent inferior laryngeal nerve (NRILN) enters the larynx directly from the vagus nerve in the cervical region. Identifying the course of the NRILN is vital to avoid injury. A case of esophageal cancer with an ARSA, in which the course of the NRILN was preserved using the Nerve Integrity Monitoring (NIM) system during surgery, is described. 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.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 2 2025 Clinical Outcomes of Neoadjuvant Paclitaxel/Cisplatin/Gemcitabine Compared with Gemcitabine/Cisplatin for Muscle-Invasive Bladder Cancer 81 92 EN Tatsushi Kawada 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 Takuji Tsugawa Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuma Tsuboi Department of Urology, Hiroshima City Hiroshima Citizens Hospital 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 Kensuke Bekku 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 Kohei Edamura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Ebara Department of Urology, Hiroshima City Hiroshima Citizens Hospital Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/68646 We retrospectively evaluated the oncologic outcomes of paclitaxel, cisplatin, and gemcitabine (PCG) with those of gemcitabine and cisplatin (GC) as neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) patients. The primary outcome was efficacy: pathological complete response (pCR), ypT0N0; and pathological objective response (pOR), ypT0N0, ≤ ypT1N0, or ypT0N1. Secondary outcomes included overall survival (OS), recurrence-free survival (RFS), predictive factors for pOR, OS, and RFS, and hematologic adverse events (AEs). Among 113 patients treated (PCG, n=28; GC, n=85), similar pOR and pCR rates were achieved by the groups (pOR: PCG, 57.1% vs. GC, 49. 4%; p=0.52; pCR: PCG, 39.3% vs. GC, 29.4%; p=0.36). No significant differences were observed in OS (p=1.0) or RFS (p=0.20). Multivariate logistic regression analysis showed that hydronephrosis (odds ratio [OR] 0.32, 95%CI: 0.11-0.92) and clinical node-positive status (cN+) (OR 0.22, 95%CI: 0.050-0.99) were significantly associated with a decreased probability of pOR. On multivariate Cox regression analyses, pOR achievement was associated with improved OS (hazard ratio [HR] 0.23, 95%CI: 0.10-0.56) and RFS (HR 0.30, 95%CI: 0.13-0.67). There were no significant between-group differences in the incidence of grade ≥ 3 hematologic AEs or dose-reduction required, but the PCG group had a higher incidence of grade 4 neutropenia. 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 5 2025 イノベーションループの実践：2024年度先進病院実習報告と未来課題 39 45 EN Nahoko HARADA Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university Satoshi TAKAHASHI Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university Tomoaki MORI Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university Haruka HIKASA Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university Keisuke SHISHIDO Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university Masaki MAGARI Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university Toyohiko WATANABE Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university Jin Wang Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university Mizuki MORITA Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university 10.18926/interdisciplinary/68625 No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 26 6 2025 Vesicular Glutamate Transporter 3 Is Involved in Glutamatergic Signalling in Podocytes 2485 EN Naoko Nishii Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Kawai Department of Cell Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Yasuoka Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Abe Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nanami Tatsumi Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuika Harada Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University Takaaki Miyaji Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University Shunai Li Center for Innovative Clinical Medicine, Okayama University Hospital Moemi Tsukano Central Research Laboratory, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Center for Innovative Clinical Medicine, Okayama University Hospital Daisuke Ogawa Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohji Takei Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Yamada Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Glomerular podocytes act as a part of the filtration barrier in the kidney. The activity of this filter is regulated by ionotropic and metabotropic glutamate receptors. Adjacent podocytes can potentially release glutamate into the intercellular space; however, little is known about how podocytes release glutamate. Here, we demonstrated vesicular glutamate transporter 3 (VGLUT3)-dependent glutamate release from podocytes. Immunofluorescence analysis revealed that rat glomerular podocytes and an immortal mouse podocyte cell line (MPC) express VGLUT1 and VGLUT3. Consistent with this finding, quantitative RT-PCR revealed the expression of VGLUT1 and VGLUT3 mRNA in undifferentiated and differentiated MPCs. In addition, the exocytotic proteins vesicle-associated membrane protein 2, synapsin 1, and synaptophysin 1 were present in punctate patterns and colocalized with VGLUT3 in MPCs. Interestingly, approximately 30% of VGLUT3 colocalized with VGLUT1. By immunoelectron microscopy, VGLUT3 was often observed around clear vesicle-like structures in differentiated MPCs. Differentiated MPCs released glutamate following depolarization with high potassium levels and after stimulation with the muscarinic agonist pilocarpine. The depletion of VGLUT3 in MPCs by RNA interference reduced depolarization-dependent glutamate release. These results strongly suggest that VGLUT3 is involved in glutamatergic signalling in podocytes and may be a new drug target for various kidney diseases. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 15 1 2025 Microfluidic fabrication of rattle shaped biopolymer microcapsules via sequential phase separation in oil droplets 6666 EN Takaichi Watanabe Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology Yuko Sakai Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology Kurumi Mori Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology Tsutomu Ono Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology Multilayer microcapsules containing a small particle within a larger capsule have recently attracted considerable attention owing to their potential applications in diverse fields, including drug delivery, active ingredient storage, and chemical reactions. These complex capsules have been fabricated using interfacial polymerization or seeded emulsion polymerization. However, these methods often require complex and lengthy polymerization processes, limiting their utility, particularly in biopolymer systems. This study introduces a simple and efficient approach for preparing rattle-shaped cellulose acetate (CA) microcapsules through sequential phase separation in droplets. We systematically examine the effects of various preparation parameters, including the amount of co-solvent, initial droplet size, and flow rates, and reveal that the incorporation of a co-solvent-ethyl acetate (EA)- in the dispersed phase significantly impacts the microcapsule morphology. Our findings demonstrate a transition from a core-shell to a rattle-shaped structure as the EA concentration increases. Furthermore, the initial droplet diameter and flow rates influence microcapsule formation-larger droplets and reduced continuous-phase flow rates favor the development of multi-layered structures. These results indicate that the formation mechanism of these rattle-shaped microcapsules arises from the establishment of a radial solvent concentration gradient and subsequent phase separation within the droplets, driven by kinetic rather than thermodynamic factors. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-1729 15 2 2025 Distinct Infection Mechanisms of Rhizoctonia solani AG-1 IA and AG-4 HG-I+II in Brachypodium distachyon and Barley 235 EN Niranjan Mahadevan Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Rozi Fernanda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yusuke Kouzai Crop Stress Management Group, Division of Plant Molecular Regulation Research, Institute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO) Natsuka Kohno Faculty of Agriculture, Okayama University Reiko Nagao Faculty of Agriculture, Okayama University Khin Thida Nyein Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Megumi Watanabe Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nanami Sakata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hidenori Matsui Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuhiro Toyoda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuki Ichinose Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Keiichi Mochida RIKEN Center for Sustainable Resource Science Hiroshi Hisano Institute of Plant Science and Resources, Okayama University Yoshiteru Noutoshi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Rhizoctonia solani is a basidiomycete phytopathogenic fungus that causes rapid necrosis in a wide range of crop species, leading to substantial agricultural losses worldwide. The species complex is divided into 13 anastomosis groups (AGs) based on hyphal fusion compatibility and further subdivided by culture morphology. While R. solani classifications were shown to be independent of host specificity, it remains unclear whether different R. solani isolates share similar virulence mechanisms. Here, we investigated the infectivity of Japanese R. solani isolates on Brachypodium distachyon and barley. Two isolates, AG-1 IA (from rice) and AG-4 HG-I+II (from cauliflower), infected leaves of both plants, but only AG-4 HG-I+II infected roots. B. distachyon accessions Bd3-1 and Gaz-4 and barley cultivar 'Morex' exhibited enhanced resistance to both isolates compared to B. distachyon Bd21 and barley cultivars 'Haruna Nijo' and 'Golden Promise'. During AG-1 IA infection, but not AG-4 HG-I+II infection, resistant Bd3-1 and Morex induced genes for salicylic acid (SA) and N-hydroxypipecolic acid (NHP) biosynthesis. Pretreatment with SA or NHP conferred resistance to AG-1 IA, but not AG-4 HG-I+II, in susceptible B. distachyon Bd21 and barley Haruna Nijo. On the leaves of susceptible Bd21 and Haruna Nijo, AG-1 IA developed extensive mycelial networks with numerous infection cushions, which are specialized infection structures well-characterized in rice sheath blight. In contrast, AG-4 HG-I+II formed dispersed mycelial masses associated with underlying necrosis. We propose that the R. solani species complex encompasses at least two distinct infection strategies: AG-1 IA exhibits a hemibiotrophic lifestyle, while AG-4 HG-I+II follows a predominantly necrotrophic strategy. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 79 1 2025 Immediate Effects of a Single Home-based Rehabilitation Treatment on Balance Performance and Toe-Grip Strength in Elderly Subjects Continuing the Same Rehabilitation Program 47 50 EN Kazunori Kojima Department of Physical Therapy, Faculty of Health Sciences, Okayama Healthcare Professional University Takuya Ujikawa Department of Physical Therapy, Faculty of Rehabilitation, Kawasaki University of Medical Welfare Toshiro Ono Department of Occupational Therapy, Faculty of Health Sciences, Okayama Healthcare Professional University Original Article 10.18926/AMO/68361 We assessed the immediate effects of a home-based rehabilitation (HBR) program on the balance performance and toe-grip strength of 29 older adults (mean±SD age of 75.1±9.9; 16 males, 13 females) who were participating in HBR services provided by Japan’s nursing care insurance system. Their toe-grip strength and balance performance were measured before and after the HBR program. The subjects’ toe-grip strength was significantly improved after the treatment. The subjects who had had a stroke showed a significant improvement after HBR. Contrarily, no significant difference was observed in the subjects’ functional reach results or their one-leg standing time. These results indicate that the exercise regimen provided in the HBR program led to increased excitability of motor units and immediately enhanced the subjects’ toe-grip strength. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 1 2025 Retrospective Analysis of the Safety of High-Volume Dental Articaine Preparations for Japanese Patients 31 37 EN Shigeru Maeda Department of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Atiphan Pimkhaokham Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chulalongkorn University Michihiro Yoshida Data Science Division, Center for Innovative Clinical Medicine, Okayama University Hospital Hiroki Hosoi Data Science Division, Center for Innovative Clinical Medicine, Okayama University Hospital Ayako Ohshima Data Science Division, Center for Innovative Clinical Medicine, Okayama University Hospital Ryoko Kurisu Department of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Nozomi Utsumi Department of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Hitoshi Higuchi Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Hospital Takuya Miyawaki Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/68356 We retrospectively analyzed the safety of the use of articaine, an amide-type local anesthetic, in Japanese dental patients (n=300) treated in Thailand in 2015-2017. The dosage, adverse events (AEs) caused by local anesthesia, and treatment efficacy were examined. Articaine, which is safe for patients with liver impairments due to its unique metabolism, has not been thoroughly tested in Japan for doses above 5.1 mL. Eighty of the present patients had undergone root canal treatment (RCT), 71 underwent tooth extraction, and 149 underwent implant-related surgery. More than three articaine cartridges were used in 41 patients, and no AEs occurred in these cases. The only AE occurred in a 52-year-old woman who was treated with three cartridges and presented with what appeared to be hyperventilation syndrome; she later recovered and received her dental treatment as scheduled. Most treatments were completed with three or fewer cartridges, suggesting that this number is generally sufficient. Our findings, particularly the low AE risk even with doses exceeding three cartridges, support the potential applicability of the overseas recommended maximum dose of articaine (7 mg/kg) in Japanese patients. This conclusion is significant for advancing dental anesthetic practices and ensuring patient safety and treatment efficacy in Japan. No potential conflict of interest relevant to this article was reported.

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

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

University of South Bohemia in Ceske Budejovice Acta Medica Okayama 1214-021X 21 2 2023 Antioxidant action of xanthine oxidase inhibitor febuxostat protects the liver and blood vasculature in SHRSP5/Dmcr rats 80 90 EN Mai Kakimoto Okayama University, Graduate School of Health Sciences, Department of Medical Technology Moe Fujii Okayama University, Graduate School of Health Sciences, Department of Medical Technology Ikumi Sato Okayama University, Graduate School of Health Sciences, Department of Medical Technology Koki Honma Okayama University, Graduate School of Health Sciences, Department of Medical Technology Hinako Nakayama Okayama University, Graduate School of Health Sciences, Department of Medical Technology Sora Kirihara Okayama University, Graduate School of Health Sciences, Department of Medical Technology Taketo Fukuoka Okayama University, Faculty of Health Sciences, Department of Medical Technology Shang Ran Okayama University, Graduate School of Health Sciences, Department of Medical Technology Satoshi Hirohata Okayama University, Academic Field of Health Science Kazuya Kitamori Kinjo Gakuin University, College of Human Life and Environment Shusei Yamamoto Okayama University, Graduate School of Health Sciences, Department of Medical Technology Shogo Watanabe Okayama University, Academic Field of Health Science Background: Xanthine oxidase (XO) generates reactive oxygen species during uric acid production. Therefore, XO inhibitors, which suppress oxidative stress, may effectively treat non-alcoholic steatohepatitis (NASH) and atherosclerosis via uric acid reduction. In this study, we examined the antioxidant effect of the XO inhibitor febuxostat on NASH and atherosclerosis in stroke-prone spontaneously hypertensive 5 (SHRSP5/Dmcr) rats.<br> Methods: SHRSP5/Dmcr rats were divided into three groups: SHRSP5/Dmcr + high-fat and high-cholesterol (HFC) diet [control group, n = 5], SHRSP5/Dmcr + HFC diet + 10% fructose (40 ml/day) [fructose group, n = 5], and SHRSP5/Dmcr + HFC diet + 10% fructose (40 ml/day) + febuxostat (1.0 mg/kg/day) [febuxostat group, n = 5]. Glucose and insulin resistance, blood biochemistry, histopathological staining, endothelial function, and oxidative stress markers were evaluated.<br> Results: Febuxostat reduced the plasma uric acid levels. Oxidative stress-related genes were downregulated, whereas antioxidant factor-related genes were upregulated in the febuxostat group compared with those in the fructose group. Febuxostat also ameliorated inflammation, fibrosis, and lipid accumulation in the liver. Mesenteric lipid deposition decreased in the arteries, and aortic endothelial function improved in the febuxostat group.<br> Conclusions: Overall, the XO inhibitor febuxostat exerted protective effects against NASH and atherosclerosis in SHRSP5/Dmcr rats. No potential conflict of interest relevant to this article was reported.

Japan Society of Plastic and Reconstructive Surgery Acta Medica Okayama 2436-259X 2 3 2023 A Case of a Transwoman with Colorectal Cancer after Flap Vaginoplasty 98 101 EN Shiho Watanabe Department of Plastic and Reconstructive Surgery, Okayama University Hospital Fuminori Teraishi Department of Minimally Invasive Therapy Center, Okayama University Hospital Sari Fujimoto Department of Plastic and Reconstructive Surgery, Okayama University Hospital Toshiyuki Watanabe Department of Plastic and Reconstructive Surgery, Okayama University Hospital Sho Takeda Department of Gastroenterological Surgery, Okayama University Hospital Shuhei Narita Department of Gastroenterological Surgery, Okayama University Hospital Koya Yamashita Department of Gastroenterological Surgery, Okayama University Hospital Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Hospital Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Hospital Yuzaburo Namba Department of Gender Center, Okayama University Hospital Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Okayama University Hospital Vaginoplasty is a gender-affirming surgery (GAS) for transwomen that laid its foundation in the 1950s and continues to be widely practiced worldwide. We present here a case of a 70-year-old transwoman who underwent lower anterior resection for rectal cancer 12 years after vaginoplasty. The preoperative diagnosis was rectal cancer (Rb-Ra, type 2, cT2N0M0, stage 1). All imaging studies showed a cord-like structure between the prostate and the anterior wall of the rectum, which was thought to be the neovagina. Careful dissection of the anterior rectal wall was required because the distance between the neovagina and the rectum was only 1.5 mm. The role of hormonal therapy and GAS in cancer development in transwomen is unclear. It is important to have regular check-ups for malignancies in patients who have undergone GAS, and if surgical procedures are needed, they should be treated by physicians who are familiar with the procedure. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0300-7839 51 4 2023 Does International Environmental Certification Change Local Production and Trade Practices? A Case Study of Shrimp Farming in Southern Vietnam 781 794 EN Hiroki Watanabe Graduate School of Environmental and Life Science, Okayama University Fumikazu Ubukata Institute of Academic and Research, Okayama University Studies on international environmental certification (IEC) have primarily focused on how certification can sustainably “upgrade” local production and trading practices. However, not many studies view this market-based governance process from the perspective of local practices and location-specific factors. This study therefore examines how the upstream of the local supply chain influenced global interventions through the case of certification for shrimp farming in the mangroves of southern Vietnam. To clarify various aspects of these interactions, semi-structured interviews were conducted with the provincial government, NGOs, a trading company, shrimp farmers, and middlemen. The results revealed that IEC did not affect local production practices and only partially influenced trade practices. The implementation of IEC was thus at the mercy of the robustness of local society, which was attributed to unique agroecology, production systems, and upstream customary economic practices. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1472-6920 25 1 2025 Effectiveness of professional-identity-formation and clinical communication-skills programs on medical students' empathy in the COVID-19 context: comparison between pre-pandemic in-person classes and during-pandemic online classes 39 EN Hitomi 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 Enhancing students' empathy is critical in medical school education. The COVID-19 pandemic necessitated a shift from in-person to online classes. However, the effectiveness of online classes for enhancing medical students' empathy has not been investigated sufficiently and the evidence is limited. This study compared the effectiveness of enhancing empathy between pre-pandemic in-person classes and during-pandemic online classes among medical students in Japan using pre-pandemic and during-pandemic data.<br> Methods This is a retrospective observational study. This study measured students' empathy using the Japanese translation of the Jefferson Scale of Empathy-Student Version (JSE-S) before and after the special programs for professional identity formation and clinical communication among first- and second-year students who matriculated from 2015-2021. This study categorized the matriculation year groups as "pre-pandemic" and "during-pandemic" groups for the first- and second-year students. This study estimated the adjusted mean score differences of the JSE-S and 95% confidence intervals (CIs) from the pre- to post-program between the pre-pandemic and during-pandemic groups in the first and second years using linear regression analysis.<br> Results This study's participants included 653 first-year students and 562 second-year students. In the first year, the during-pandemic group had a significantly higher mean score difference from the pre- to post-program compared to the pre-pandemic group. The adjusted regression coefficient (95% CI) was 7.6 (5.7 - 9.5), with the pre-pandemic group as the reference. In the second year, there were no significant differences between the two groups.<br> Conclusions The results suggest that online classes are not inferior to in-person classes or even slightly better in enhancing medical students' empathy, which should be clarified by further studies. This study's findings have important implications for medical education and implementing hybrid class formats to enhance students' empathy. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 1664-2392 15 2024 HOMA-beta independently predicts survival in patients with advanced cancer on treatment with immune checkpoint inhibitors 1439705 EN Mayu Watanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Eguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Takamoto Department of Urology, Fukuyama City Hospital Hiromitsu Kanzaki Department of Internal Medicine, Tsuyama Chuo Hospital Yohei Noda Department of Urology, Fukuyama City Hospital Syunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Although immune checkpoint inhibitors (ICIs) are effective cancer drugs, ICI-induced diabetes is a rare but a life-threatening adverse event for patients. The deleterious action of ICI on pancreatic beta-cell function is a concern. However, the influence of ICI on insulin synthesis and secretion in patients with cancer without diabetes remains unknown. <br> Methods: This study included 87 patients diagnosed with advanced cancer. Glucose metabolism markers (HbA1c, HOMA-IR) and indicators of insulin secretory capacity (HOMA-beta, C-peptide) were prospectively evaluated in patients with ICI-treated cancers to determine their association with cancer prognosis. <br> Results: Patients with overall survival (OS) >= 7 months had substantially higher HOMA-beta levels at baseline (p=0.008) and 1 month after ICI administration (p=0.006) compared to those with OS <7 months. The median OS was significantly longer in patients with HOMA-beta >= 64.24 (13 months, 95%CI: 5.849-20.151, 37 events) than in those with HOMA-beta < 64.24 (5 months, 95%CI: 3.280-6.720, 50 events) (p=0.013). Further, the median progression-free survival (PFS) was significantly longer in patients with HOMA-beta >= 66.43 (4 months, 95%CI: 3.073-4.927, 33 events) than in those with HOMA-beta < 66.43 (2 months, 95%CI: 1.410-2.590, 54 events) (p=0.025). Additionally, multivariable logistic regression analysis revealed that a HOMA-beta value >= 64.24 independently predicted longer OS in ICI-treated patients. <br> Conclusions: Pre-ICI HOMA-beta level is linked to longer OS in ICI-treated patients. This connection is significant and shows that insulin secretory capacity may predict ICI efficacy. No potential conflict of interest relevant to this article was reported.

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

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 4 2025 古代越前国足羽郡の「郡的世界」寸考 80 90 EN Atsunori WATANABE Chigasaki City Museum 研究ノート (Research note) 10.18926/67957 　Often discussed in recent years, the term gun-teki sekai refers to the social conditions of a district. In ancient Japanese local communities, there existed complex webs of historical rule and intertwined relationships between local clans that date back to before the establishment of the Ritsuryō system. Gun-teki sekai is a term that refers to the reality of the control of the provincial and district systems, in which multiple powerful clans served as gunji , district governors under the Ritsuryō system. Each gunji organized smaller clans below them to carry out administrative duties based on such relationships. Recent research is beginning to reveal the multipolar structure of the gun-teki sekai .<br> 　In this study, the author examines the gun-teki sekai through an analysis of the Asuwa district in Echizen province, which is rich in historical materials. As a result, the following four points became clear. First, it is highly likely that the powerful clans who served as district governors in the mid-Nara period were traditional clans with roots in the eastern part of the district. Second, the powerful clans who served as district deputy governors may have been an emerging power. Third, from an archaeological perspective, the eastern part of the district is the traditional area, while the dominance of the western part of the district developed after the establishment of the Ritsuryō system. Fourth, in terms of clan distribution, the clans who served as district governors were distributed over the widest area, followed by those who served as district deputy governors. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 136 3 2024 令和５年度岡山医学会賞　総合研究奨励賞（結城賞） 91 93 EN Haruki Watanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 6 2024 Case of Radiation-Induced Angiosarcoma after Breast-Conserving Surgery with Hypofractionated Radiotherapy in a Japanese Patient 453 458 EN Yujiro Kawata Department of Radiology, Kawasaki Medical School Kenta Watanabe Department of Radiology, Kawasaki Medical School Ryoji Tokiya Department of Radiology, Kawasaki Medical School Takeshi Matsuno Department of Pathology, Kawasaki Medical School Ryo Tanaka Department of Dermatology, Kawasaki Medical School Naruto Taira Department of Breast and Thyroid Surgery, Kawasaki Medical School Kuniaki Katsui Department of Radiology, Kawasaki Medical School Case Report 10.18926/AMO/67871 Radiation-induced angiosarcoma (RIAS) is a rare, late adverse event of radiotherapy comprising approximately half of all radiation-induced sarcomas. It has a relatively short latency period and generally unfavorable prognosis. This study presents a case of RIAS that developed 5 years and 11 months after the completion of hypofractionated radiotherapy (42.56 Gy/16 fractions) following partial mastectomy. The patient was diagnosed with RIAS 10 months after the onset of skin redness. She underwent skin tumor resection, followed by paclitaxel, then pazopanib administration, but no radiotherapy. At 6 years and 2 months after surgery, no RIAS recurrence has been detected. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 6 2024 Closure of Ventricular Septal Rupture through a Left Thoracotomy in a Patient with a History of Esophageal Reconstruction 449 452 EN Gentaro Kato Department of Cardiovascular Surgery, Kagawa Prefectural Central Hospital Tatsuya Ogawa Department of Cardiovascular Surgery, Kagawa Prefectural Central Hospital Tomohiro Hayashida Department of Cardiovascular Surgery, Kagawa Prefectural Central Hospital Shuji Shimizu Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Shu Yamamoto Department of Cardiovascular Surgery, Kagawa Prefectural Central Hospital Takeshi Shichijo Department of Cardiovascular Surgery, Kagawa Prefectural Central Hospital Case Report 10.18926/AMO/67870 A 73-year-old man who had undergone esophagectomy and retrosternal gastric tube reconstruction for esophageal cancer 8 years prior was transferred to our hospital for the treatment of an acute myocardial infarction. Emergent percutaneous coronary intervention for the left anterior descending artery (#7) was successfully performed. However, echocardiography revealed a ventricular septal rupture (25×27 mm). Seventeen days after admission, the rupture was successfully treated with a double-patch closure via a left anterolateral thoracotomy to avoid a surgical injury to his retrosternal gastric tube. Determining the best surgical approach to the heart is important for safe cardiac surgery in patients after esophageal reconstruction. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 6 2024 Partial versus Radical Nephrectomy for Small Renal Cancer: Comparative Propensity Score-Matching Analysis of Cardiovascular Event Risk 429 437 EN Risa Kubota 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 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 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 Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/67868 Although partial nephrectomy (PN) is preferred over radical nephrectomy (RN) for preserving renal function in patients with cT1 renal cancer, its impact on cardiovascular events (CVe) remains controversial. This study aimed to compare PN and RN in regard to the occurrence of CVe, including cerebrovascular events and exacerbation of hypertension (HT). We retrospectively analyzed 418 consecutive patients who underwent PN or RN for cT1 renal cancer. Propensity score-matching analysis was used to adjust for imbalances between patients who underwent PN and RN, leaving 102 patients in each group. The 5-year probability of cumulative CVe incidence was 6% in the PN group and 12% in the RN group (p=0.03), with a median follow-up of 73.5 months. The statistical significance was retained after propensity score matching for patients without preoperative proteinuria (p=0.03). For all CVe including cerebrovascular events and exacerbation of HT analyzed, PN provided a lower probability of occurrence than RN in patients with small renal cancers. No potential conflict of interest relevant to this article was reported.

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

American Chemical Society (ACS) Acta Medica Okayama 0743-7463 40 43 2024 Nanoscale Structures of Tough Microparticle-Based Films Investigated by Synchrotron X-Ray Scattering and All-Atom Molecular-Dynamics Simulation 22614 22626 EN Keita Namba Department of Frontier Materials Chemistry, Graduate School of Science and Technology, Hirosaki University Yuma Sasaki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuto Kawamura Graduate School of Textile Science &Technology, Shinshu University Shotaro Yoshida Department of Materials Chemistry, Nagoya University Yoshiki Hieda Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials and Bioengineering, Kansai University Kazushi Fujimoto Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials and Bioengineering, Kansai University Natsuki Watanabe Department of Physics, Nagoya University Yuichiro Nishizawa Department of Physics, Nagoya University Takayuki Uchihashi Department of Physics, Nagoya University Daisuke Suzuki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takuma Kureha Department of Frontier Materials Chemistry, Graduate School of Science and Technology, Hirosaki University In this study, the nanoscale structures of microparticle-based films are revealed by synchrotron small-angle X-ray scattering (SAXS) and all-atom molecular-dynamics (AA-MD) simulations. The microparticle-based films consisting of the simplest acrylate polymer microparticles are applied as a model because the films are formed without additives and organic solvents and exhibit high toughness properties. The characteristic interfacial thickness (tinter) obtained from the SAXS analysis reflects the mixing degree of polymer chains on the microparticle surface in the film. The cross-linking density of inner microparticles is found to be strongly correlated to not only several properties of individual microparticles, such as swelling ratio and radius of gyration, but also the tinter and toughness of the corresponding films. Therefore, the tinter and toughness values follow a linear relationship because the cross-linking restricts the mixing of polymer chains between their surfaces in the film, which is a unique feature of microparticle-based films. This characteristic also affects their deformation behavior observed by in situ SAXS during tensile testing and their density profiles calculated by AA-MD simulations. This work provides a general strategy for material design to control the physical properties and structures of their films for advanced applications, including volatile organic compound-free sustainable coatings and adhesives. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 1022-1336 46 1 2024 Elastomer Particle Monolayers Formed by the Compression of Poly(methyl acrylate) Microparticles at an Air/Water Interface 2400604 EN Yuma Sasaki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuichiro Nishizawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Natsuki Watanabe Department of Physics, Nagoya University Takayuki Uchihashi Department of Physics, Nagoya University Daisuke Suzuki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University In the previous study (Green Chem., 2023, 25, 3418), highly stretchable and mechanically tough poly(methyl acrylate) (pMA) microparticle-based elastomers can be formed by drying a microparticle-containing aqueous dispersion. This discovery has the potential to overcome the mechanical weakness of industrially produced aqueous latex films. However, in 3D-arranged particle films, structural complexity, such as the existence of defects, makes it difficult to clearly understand the relationship between the particle film structure and its mechanical properties. In this study, 2D-ordered pMA particle monolayers at the air/water interface of a Langmuir trough are prepared. Under high compression at the air/water interface, the microparticles contact their neighboring particles, and the resulting monolayers can be successfully transferred onto a solid substrate. The compression of the monolayer films is linked to an increase in the elastic modulus of the monolayer film on the solid substrate as evident from the local Young's modulus mapping using atomic force microscopy. Thus, pMA particle films with different mechanical properties can be created using a Langmuir trough. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0032-0781 65 11 2024 Nutrient Requirements Shape the Preferential Habitat of Allorhizobium vitis VAR03-1, a Commensal Bacterium, in the Rhizosphere of Arabidopsis thaliana 1769 1786 EN Niarsi Merry Hemelda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Jiyuan Bao Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Megumi Watanabe Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hidenori Matsui Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuhiro Toyoda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuki Ichinose Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiteru Noutoshi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University A diverse range of commensal bacteria inhabit the rhizosphere, influencing host plant growth and responses to biotic and abiotic stresses. While root-released nutrients can define soil microbial habitats, the bacterial factors involved in plant–microbe interactions are not well characterized. In this study, we investigated the colonization patterns of two plant disease biocontrol agents, Allorhizobium vitis VAR03-1 and Pseudomonas protegens Cab57, in the rhizosphere of Arabidopsis thaliana using Murashige and Skoog (MS) agar medium. VAR03-1 formed colonies even at a distance from the roots, preferentially in the upper part, while Cab57 colonized only the root surface. The addition of sucrose to the agar medium resulted in excessive proliferation of VAR03-1, similar to its pattern without sucrose, whereas Cab57 formed colonies only near the root surface. Overgrowth of both bacterial strains upon nutrient supplementation inhibited host growth, independent of plant immune responses. This inhibition was reduced in the VAR03-1 ΔrecA mutant, which exhibited increased biofilm formation, suggesting that some activities associated with the free-living lifestyle rather than the sessile lifestyle may be detrimental to host growth. VAR03-1 grew in liquid MS medium with sucrose alone, while Cab57 required both sucrose and organic acids. Supplementation of sugars and organic acids allowed both bacterial strains to grow near and away from Arabidopsis roots in MS agar. These results suggest that nutrient requirements for bacterial growth may determine their growth habitats in the rhizosphere, with nutrients released in root exudates potentially acting as a limiting factor in harnessing microbiota. No potential conflict of interest relevant to this article was reported.

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

Nature Portfolio Acta Medica Okayama 2041-1723 15 1 2024 Controlling 229Th isomeric state population in a VUV transparent crystal 5536 EN Takahiro Hiraki Research Institute for Interdisciplinary Science, Okayama University Koichi Okai Research Institute for Interdisciplinary Science, Okayama University Michael Bartokos Institute for Atomic and Subatomic Physics, TU Wien Kjeld Beeks Institute for Atomic and Subatomic Physics, TU Wien Hiroyuki Fujimoto National Institute of Advanced Industrial Science and Technology (AIST) Yuta Fukunaga Research Institute for Interdisciplinary Science, Okayama University Hiromitsu Haba RIKEN Yoshitaka Kasamatsu Graduate School of Science, Osaka University Shinji Kitao Institute for Integrated Radiation and Nuclear Science, Kyoto University Adrian Leitner Institute for Atomic and Subatomic Physics, TU Wien Takahiko Masuda Research Institute for Interdisciplinary Science, Okayama University Ming Guan Research Institute for Interdisciplinary Science, Okayama University Nobumoto Nagasawa Japan Synchrotron Radiation Research Institute Ryoichiro Ogake Research Institute for Interdisciplinary Science, Okayama University Martin Pimon Institute for Atomic and Subatomic Physics, TU Wien Martin Pressler Institute for Atomic and Subatomic Physics, TU Wien Noboru Sasao Research Institute for Interdisciplinary Science, Okayama University Fabian Schaden Institute for Atomic and Subatomic Physics, TU Wien Thorsten Schumm Institute for Atomic and Subatomic Physics, TU Wien Makoto Seto Institute for Integrated Radiation and Nuclear Science, Kyoto University Yudai Shigekawa RIKEN Kotaro Shimizu Research Institute for Interdisciplinary Science, Okayama University Tomas Sikorsky Institute for Atomic and Subatomic Physics, TU Wien Kenji Tamasaku RIKEN SPring-8 Center Sayuri Takatori Research Institute for Interdisciplinary Science, Okayama University Tsukasa Watanabe National Institute of Advanced Industrial Science and Technology (AIST) Atsushi Yamaguchi RIKEN Yoshitaka Yoda Japan Synchrotron Radiation Research Institute Akihiro Yoshimi Research Institute for Interdisciplinary Science, Okayama University Koji Yoshimura Research Institute for Interdisciplinary Science, Okayama University The radioisotope thorium-229 (Th-229) is renowned for its extraordinarily low-energy, long-lived nuclear first-excited state. This isomeric state can be excited by vacuum ultraviolet (VUV) lasers and Th-229 has been proposed as a reference transition for ultra-precise nuclear clocks. To assess the feasibility and performance of the nuclear clock concept, time-controlled excitation and depopulation of the Th-229 isomer are imperative. Here we report the population of the Th-229 isomeric state through resonant X-ray pumping and detection of the radiative decay in a VUV transparent Th-229-doped CaF2 crystal. The decay half-life is measured to 447(25) s, with a transition wavelength of 148.18(42) nm and a radiative decay fraction consistent with unity. Furthermore, we report a new "X-ray quenching" effect which allows to de-populate the isomer on demand and effectively reduce the half-life. Such controlled quenching can be used to significantly speed up the interrogation cycle in future nuclear clock schemes. No potential conflict of interest relevant to this article was reported.

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

MDPI Acta Medica Okayama 1420-3049 29 11 2024 In Vitro Study of Tumor-Homing Peptide-Modified Magnetic Nanoparticles for Magnetic Hyperthermia 2632 EN Shengli Zhou Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kaname Tsutsumiuchi College of Bioscience and Biotechnology, Chubu University Ritsuko Imai College of Bioscience and Biotechnology, Chubu University Yukiko Miki College of Bioscience and Biotechnology, Chubu University Anna Kondo College of Bioscience and Biotechnology, Chubu University Hiroshi Nakagawa College of Bioscience and Biotechnology, Chubu University Kazunori Watanabe Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takashi Ohtsuki Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Cancer cells have higher heat sensitivity compared to normal cells; therefore, hyperthermia is a promising approach for cancer therapy because of its ability to selectively kill cancer cells by heating them. However, the specific and rapid heating of tumor tissues remains challenging. This study investigated the potential of magnetic nanoparticles (MNPs) modified with tumor-homing peptides (THPs), specifically PL1 and PL3, for tumor-specific magnetic hyperthermia therapy. The synthesis of THP-modified MNPs involved the attachment of PL1 and PL3 peptides to the surface of the MNPs, which facilitated enhanced tumor cell binding and internalization. Cell specificity studies revealed an increased uptake of PL1- and PL3-MNPs by tumor cells compared to unmodified MNPs, indicating their potential for targeted delivery. In vitro hyperthermia experiments demonstrated the efficacy of PL3-MNPs in inducing tumor cell death when exposed to an alternating magnetic field (AMF). Even without exposure to an AMF, an additional ferroptotic pathway was suggested to be mediated by the nanoparticles. Thus, this study suggests that THP-modified MNPs, particularly PL3-MNPs, hold promise as a targeted approach for tumor-specific magnetic hyperthermia therapy. No potential conflict of interest relevant to this article was reported.

Hindawi Acta Medica Okayama 2090-8113 2024 2024 Circadian Rhythms Fluctuate the Treatment Effects of Intravesical Treatments on Rat Urinary Frequency Models 6505595 EN Tomofumi Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Tominaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Maruyama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoya Nagasaki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takanori Sekito 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 Toyohiko Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objectives. It is still not clear how the intravesical instillation of drugs affects rat urinary frequency. This study aimed to examine the dynamics of intravesical treatments' treatment effect on rat urinary frequency models by real-time and extended monitoring using a novel continuous urination monitoring system. Methods. Nine eleven-week-old female Wistar rats were divided into three groups to receive intravesical instillation of 0.1% acetic acid (AA), 1.0% AA, or phosphate-buffered saline (PBS). Thirty minutes later, these drugs were voided, and rats were moved to a continuous urination monitoring system, UM-100. UM-100 monitored rat urination quantitatively and continuously for 24 hours. Rats were then euthanized, and histopathologic examinations using a damage score validated the severity of bladder inflammation. We used nine additional rats to determine the treatment effect of various drugs against the urinary frequency. These rats were also treated with 1.0% AA in the same way and divided into three groups (n = 3 each) to receive intravesical instillation of lidocaine, silver nitrate (AgNO3), or dimethyl sulfoxide (DMSO), respectively. Thirty minutes later, rats were catheterized again and moved to the UM-100, and their voiding was monitored for 24 hours. Results. Intravesical instillation of AA increased the urinary frequency and decreased the mean voided volume (VV) in a concentration-dependent manner, with statistical significance at a concentration of 1.0% (urinary frequency; p = 0.0007 , mean VV; p = 0.0032 , respectively) compared with PBS. Histopathological analysis of these models demonstrated a significantly higher damage score of bladder mucosa in both 0.1% AA and 1.0% AA compared with PBS, with the severity in concordance with the clinical severity of urinary frequency (0.1% AA: p < 0.0001 , 1.0% AA: p < 0.0001 ). Moreover, intravesical instillation of lidocaine, AgNO3, and DMSO decreased the urinary frequency. Continuous monitoring with UM-100 also demonstrated that the treatment effect of these intravesically instilled drugs occurred only at night. Conclusions. The extended monitoring of rat urination by UM-100 revealed a significant fluctuation in the treatment effect of intravesically instilled drugs between day and night. These findings may help establish novel therapies for urinary frequency. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 3 2024 Calcification of a Hydrophilic Acrylic Intraocular Lens after Glaucoma Surgery 295 300 EN Sara Okamoto Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Shiode Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Kimura Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mio Hosokawa Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Kanzaki Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroya Kindo Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuro Morita Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Tsuji Fukuyama City Hospital Kosuke Takahashi Fukuyama City Hospital Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/67206 A Japanese woman in her 70s was referred to our hospital for the evaluation and treatment of high intraocular pressure (IOP) in her right eye. She had undergone bilateral cataract surgeries and the insertion of hydrophilic acrylic intraocular lenses (IOLs). We performed trabeculotomy and trabeculectomy to lower her right IOP; thereafter, a circular opacity was observed on the right eye’s IOL surface. We removed the right IOL because that eye’s vision had decreased due to IOL opacification. The analysis of the removed IOL revealed that the main opacity component was calcium phosphate. This is the first post-glaucoma-surgery IOL calcification case report. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 78 3 2024 Effect of Lipopolysaccharide on the Duration of Zolpidem-Induced Loss of Righting Reflex in Mice 227 235 EN Yudai Wada Department of Clinical Pharmacy, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Ushio Department of Pharmacy, Okayama University Hospital Yoshihisa Kitamura Department of Clinical Pharmacy, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshito Zamami Department of Clinical Pharmacy, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Sendo Department of Clinical Pharmacy, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/67197 Zolpidem, a non-benzodiazepine hypnotic, is primarily used to treat insomnia. In a previous study, pior treatment with non-benzodiazepine receptor agonists was associated with inflammation. The present study aimed to clarify the association between the effects of zolpidem and inflammation in mice treated with lipopolysaccharide (LPS), a known model of inflammation. We assessed the zolpidem-induced loss of righting reflex (LORR) duration 24 h after LPS treatment in mice. Additionally, the expressions of γ-aminobutyric acid (GABA)A receptor subunit and K+-Cl− cotransporter isoform 2 (KCC2) mRNA in the hippocampus and frontal cortex were examined in LPS-treated mice. Pretreatment with LPS was associated with significantly prolonged duration of zolpidem-induced LORR compared to control mice. This effect was significantly attenuated by administering bicuculline, a GABAA receptor antagonist, or flumazenil, a benzodiazepine receptor antagonist, in LPS-treated mice. Compared to controls, LPS-treated mice showed no significant change in the expression of GABAA receptor subunits in the hippocampus or frontal cortex. Bumetanide, an Na+-K+-2Cl− cotransporter isoform 1 blocker, attenuated the extended duration of zolpidem-induced LORR observed in LPS-treated mice. LPS significantly decreased Kcc2 mRNA expression in the hippocampus and the frontal cortex. These findings suggest that inflammation increases zolpidem-induced LORR, possibly through a reduction in KCC2 expression. No potential conflict of interest relevant to this article was reported.

BMJ Publishing Group Acta Medica Okayama 2052-4897 12 3 2024 Plasma angiotensin-converting enzyme 2 (ACE2) is a marker for renal outcome of diabetic kidney disease (DKD) (U-CARE study 3) e004237 EN Asami Ueno Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Yasuhiro Onishi Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Koki Mise Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Satoshi Yamaguchi Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Ayaka Kanno Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Ichiro Nojima Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Chigusa Higuchi Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Kenichi Shikata Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Satoshi Miyamoto Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Atsuko Nakatsuka Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Jun Eguchi Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Kazuyuki Hida Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center Akihiro Katayama Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center Mayu Watanabe Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center Tatsuaki Nakato Department of Internal Medicine, Okayama Saiseikai General Hospital Atsuhito Tone Department of Internal Medicine, Okayama Saiseikai General Hospital Sanae Teshigawara Okayama Saiseikai General Hospital Takashi Matsuoka Department of Diabetic Medicine, Kurashiki Central Hospital Shinji Kamei Department of Diabetic Medicine, Kurashiki Central Hospital Kazutoshi Murakami Department of Diabetic Medicine, Kurashiki Central Hospital Ikki Shimizu Sakakibara Heart Institute of Okayama Katsuhito Miyashita Japanese Red Cross Okayama Hospital Shinichiro Ando Okayama City General Medical Center Tomokazu Nunoue Nunoue Clinic Jun Wada Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Introduction ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not.<br> Research design and methods Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year.<br> Results The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR.<br> Conclusions Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD.Trial registration number UMIN000011525. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 The Relationships among Internalized Stigma, Sense of Coherence, and Personal Recovery of Persons with Schizophrenia Living in the Community EN Aya KURAMOTO Graduate School of Health Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Etiology of recurrent cystitis in postmenopausal women based on vaginal microbiota and the role of Lactobacillus vaginal suppository EN Takanori SEKITO Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 The Genotypic and Phenotypic Characteristics Contributing to Flomoxef Sensitivity in Clinical Isolates of ESBL-Producing E.coli Strains from Urinary Tract Infections EN Kazuma SAKAEDA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Promising Gene Therapy Using an Adenovirus Vector Carrying REIC/Dkk-3 Gene for the Treatment of Biliary Cancer EN Emi TANAKA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Postnatal longitudinal analysis of serum nitric oxide and eosinophil counts in extremely preterm infants EN Hirokazu WATANABE Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Reduced Immunogenicity of COVID-19 Vaccine in Obese Patients with Type 2 Diabetes: A Cross-Sectional Study EN Hiroko TAKAHASHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1932-7447 127 25 2023 Li-Ion Transport and Solution Structure in Sulfolane-Based Localized High-Concentration Electrolytes 12295 12303 EN Taku Sudoh Taku Sudoh Department of Chemistry and Life Science, Yokohama National University Shuhei Ikeda Department of Materials Chemistry, Nagoya University Keisuke Shigenobu Department of Chemistry and Life Science, Yokohama National University Seiji Tsuzuki Advanced Chemical Energy Research Centre (ACERC), Institute of Advanced Sciences, Yokohama National University Kaoru Dokko Department of Chemistry and Life Science, Yokohama National University Masayoshi Watanabe Advanced Chemical Energy Research Centre (ACERC), Institute of Advanced Sciences, Yokohama National University Wataru Shinoda Research Institute for Interdisciplinary Science and Department of Chemistry, Okayama University Kazuhide Ueno Department of Chemistry and Life Science, Yokohama National University Localized high-concentration electrolytes (LHCEs), which are mixtures of highly concentrated electrolytes (HCEs) and non-coordinating diluents, have attracted significant interest as promising liquid electrolytes for next-generation Li secondary batteries, owing to their various beneficial properties both in the bulk and at the electrode/electrolyte interface. We previously reported that the large Li+-ion transference number in sulfolane (SL)-based HCEs, attributed to the unique exchange/hopping-like Li+-ion conduction, decreased upon dilution with the non-coordinating hydrofluoroether (HFE) despite the retention of the local Li+-ion coordination structure. Therefore, in this study, we investigated the effects of HFE dilution on the Li+ transference number and the solution structure of SL-based LHCEs via the analysis of dynamic ion correlations and molecular dynamics simulations. The addition of HFE caused nano-segregation in the SL-based LHCEs to afford polar and nonpolar domains and fragmentation of the polar ion-conducting pathway into smaller clusters with increasing HFE content. Analysis of the dynamic ion correlations revealed that the anti-correlated Li+–Li+ motions were more pronounced upon HFE addition, suggesting that the Li+ exchange/hopping conduction is obstructed by the non-ion-conducting HFE-rich domains. Thus, the HFE addition affects the entire solution structure and ion transport without significantly affecting the local Li+-ion coordination structure. Further studies on ion transport in LHCEs would help obtain a design principle for liquid electrolytes with high ionic conductivity and large Li+-ion transference numbers. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0946-2716 101 4 2023 Novel extracellular role of REIC/Dkk-3 protein in PD-L1 regulation in cancer cells 431 447 EN Yuma Gohara Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Nahoko Tomonobu Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Rie Kinoshita Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Junichiro Futami Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Léna Audebert Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Youyi Chen Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ni Luh Gede Yoni Komalasari Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Fan Jiang Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Chikako Yoshizawa Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hitoshi Murata Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ken-ichi Yamamoto Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masami Watanabe Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hiromi Kumon Innovation Center Okayama for Nanobio-Targeted Therapy, Okayama University Masakiyo Sakaguchi Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine The adenovirus-REIC/Dkk-3 expression vector (Ad-REIC) has been the focus of numerous clinical studies due to its potential for the quenching of cancers. The cancer-suppressing mechanisms of the REIC/DKK-3 gene depend on multiple pathways that exert both direct and indirect effects on cancers. The direct effect is triggered by REIC/Dkk-3-mediated ER stress that causes cancer-selective apoptosis, and the indirect effect can be classified in two ways: (i) induction, by Ad-REIC-mis-infected cancer-associated fibroblasts, of the production of IL-7, an important activator of T cells and NK cells, and (ii) promotion, by the secretory REIC/Dkk-3 protein, of dendritic cell polarization from monocytes. These unique features allow Ad-REIC to exert effective and selective cancer-preventative effects in the manner of an anticancer vaccine. However, the question of how the REIC/Dkk-3 protein leverages anticancer immunity has remained to be answered. We herein report a novel function of the extracellular REIC/Dkk-3—namely, regulation of an immune checkpoint via modulation of PD-L1 on the cancer-cell surface. First, we identified novel interactions of REIC/Dkk-3 with the membrane proteins C5aR, CXCR2, CXCR6, and CMTM6. These proteins all functioned to stabilize PD-L1 on the cell surface. Due to the dominant expression of CMTM6 among the proteins in cancer cells, we next focused on CMTM6 and observed that REIC/Dkk-3 competed with CMTM6 for PD-L1, thereby liberating PD-L1 from its complexation with CMTM6. The released PD-L1 immediately underwent endocytosis-mediated degradation. These results will enhance our understanding of not only the physiological nature of the extracellular REIC/Dkk-3 protein but also the Ad-REIC-mediated anticancer effects. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1873-734X 63 3 2023 Surgical outcome of ipsilateral anatomical resection for lung cancer after pulmonary lobectomy ezad048 EN Mikio Okazaki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Suzawa Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiko Shien Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiromasa Yamamoto Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Araki Okayama University Thoracic Surgery Study Group (OUTSSG) Mototsugu Watanabe Okayama University Thoracic Surgery Study Group (OUTSSG) Masanori Okada Okayama University Thoracic Surgery Study Group (OUTSSG) Yuho Maki Okayama University Thoracic Surgery Study Group (OUTSSG) Tsuyoshi Ueno Okayama University Thoracic Surgery Study Group (OUTSSG) Shinji Otani Okayama University Thoracic Surgery Study Group (OUTSSG) Ryujiro Sugimoto Okayama University Thoracic Surgery Study Group (OUTSSG) Hitoshi Nishikawa Okayama University Thoracic Surgery Study Group (OUTSSG) Riki Okita Okayama University Thoracic Surgery Study Group (OUTSSG) Makio Hayama Okayama University Thoracic Surgery Study Group (OUTSSG) Hiroyuki Tao Okayama University Thoracic Surgery Study Group (OUTSSG) Toshiya Fujiwara Okayama University Thoracic Surgery Study Group (OUTSSG) Hidetoshi Inokawa Okayama University Thoracic Surgery Study Group (OUTSSG) Yuji Hirami Okayama University Thoracic Surgery Study Group (OUTSSG) Yoshifumi Sano Okayama University Thoracic Surgery Study Group (OUTSSG) Motohiro Yamashita Okayama University Thoracic Surgery Study Group (OUTSSG) Osamu Kawamata Okayama University Thoracic Surgery Study Group (OUTSSG) Motoki Matsuura Okayama University Thoracic Surgery Study Group (OUTSSG) Shinichi Toyooka Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University OBJECTIVES: Ipsilateral reoperation after pulmonary lobectomy is often challenging because of adhesions from the previous operation. We retrospectively examined the surgical outcome and prognosis of ipsilateral anatomical resection for lung cancer after pulmonary lobectomy using a multicentre database.<br> METHODS: We evaluated the perioperative outcomes and overall survival of 51 patients who underwent pulmonary lobectomy followed by ipsilateral anatomical resection for lung cancer between January 2012 and December 2018. In addition, patients with stage I non-small-cell lung cancer (NSCLC) were compared with 3411 patients with stage I lung cancer who underwent pulmonary resection without a prior ipsilateral lobectomy.<br> RESULTS: Ipsilateral anatomical resections included 10 completion pneumonectomies, 19 pulmonary lobectomies and 22 pulmonary segmentectomies. Operative time was 312.2 ± 134.5 min, and intraoperative bleeding was 522.2 ± 797.5 ml. Intraoperative and postoperative complications occurred in 9 and 15 patients, respectively. However, the 5-year overall survival rate after anatomical resection followed by ipsilateral lobectomy was 83.5%. Furthermore, in patients with c-stage I NSCLC, anatomical resection followed by ipsilateral lobectomy was not associated with worse survival than anatomical resection without prior ipsilateral lobectomy.<br> CONCLUSIONS: Anatomical resection following ipsilateral lobectomy is associated with a high frequency of intraoperative and postoperative complications. However, the 5-year overall survival in patients with c-stage I NSCLC who underwent ipsilateral anatomical resection after pulmonary lobectomy is comparable to that in patients who underwent anatomical resection without prior pulmonary lobectomy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 Perineal Squamous Cell Carcinoma Arising in an Epidermal Cyst 197 200 EN Fuminori Teraishi 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 Kota Tachibana Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Watanabe Department of Plastic and Reconstructive Surgery, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/66930 A 90-year-old Japanese woman who had been aware of a subcutaneous mass on the right perineal region for 5 years was referred to our hospital for further examination and treatment because of the rapid growth of the mass and bleeding that began 3 months earlier. A biopsy of the mass revealed a diagnosis of well-differentiated squamous cell carcinoma. On preoperative examination, the tumor was 90×40 mm in size and was suspected to have partially invaded the levator ani muscle and external sphincter. Since a preoperative cardiac evaluation indicated severe aortic stenosis, we performed transcatheter aortic valve implantation. A radical resection was then performed with general anesthesia. The skin and subcutaneous tissue defects were reconstructed with a posterior gluteal-thigh propeller flap, and a sigmoid colostomy was created. The patient had a good postoperative course and was transferred to a rehabilitation facility 28 days after the surgery. Epidermal cysts are a common benign tumor, and clinicians should keep in mind that these cysts can become malignant. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 Laparoscopic Resection Combined with a Transsacral Approach for a Recurrent Tailgut Cyst with a Refractory Fistula 193 196 EN Hajime Kashima 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 Yuki Matsumi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Shimamura Department of Surgery, Chikuba Hospital for Gastrointestinal and Colorectal Surgery Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/66928 Tailgut cyst is a rare cystic disease of the anterior sacral surface and the remains of an embryonic tail gut. Tailgut cysts have a potential for malignancy, and complete resection with an adequate surgical margin is necessary. Even if incomplete resection does not result in recurrence of malignant disease, there is a risk of local infection leading to refractory fistulas. The optimal treatment for such refractory recurrent lesions has not been reported. We describe a case in which the combination of laparoscopic and transsacral approaches was effective for resecting a recurrent refractory fistula after incomplete resection of a tail gut cyst. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 Reduced Immunogenicity of COVID-19 Vaccine in Obese Patients with Type 2 Diabetes: A Cross-Sectional Study 185 191 EN Hiroko Takahashi Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Eguchi Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mayu Watanabe Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Nakayama Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/66927 The global pandemic of coronavirus infection 2019 (COVID-19) was an unprecedented public health emergency. Several clinical studies reported that heart disease, lung disease, diabetes, hypertension, dyslipidemia, and obesity are critical risk factors for increased severity of and hospitalization for COVID-19. This is largely because patients with these underlying medical conditions can show poor immune responses to the COVID-19 vaccinations. Diabetes is one of the underlying conditions most highly associated with COVID-19 susceptibility and is considered a predictor of poor prognosis of COVID-19. We therefore investigated factors that influence the anti-SARS-CoV-2 spike IgG antibody titer after three doses of vaccination in patients with type 2 diabetes. We found that obesity was associated with low anti-SARS-CoV-2 spike IgG antibody titers following three-dose vaccination in type 2 diabetics. Obese patients with type 2 diabetes may have attenuated vaccine efficacy and require additional vaccination; continuous infection control should be considered in such patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 The Relationships among Internalized Stigma, Sense of Coherence, and Personal Recovery of Persons with Schizophrenia Living in the Community 171 184 EN Aya Kuramoto Graduate School of Health Sciences, Okayama University Shinya Saito Graduate School of Health Sciences, Okayama University Kumi Watanabe School of Nursing, Faculty of Medicine, Kagawa University Original Article 10.18926/AMO/66926 We investigated (i) the relationships among internalized stigma (IS), sense of coherence (SOC), and the personal recovery (PR) of persons with schizophrenia living in the community, and (ii) how to improve the support for these individuals. A questionnaire survey on IS, SOC, and PR was sent by mail to 270 persons with schizophrenia living in the community who were using psychiatric daycare services, of whom 149 responded and 140 were included in the analysis. We established a hypothetical model in which IS influences PR, and SOC influences IS and PR, and we used structural equation modeling to examine the relationships among these concepts. The goodness of fit was acceptable. Our findings suggest that rather than directly promoting PR, SOC promotes PR by mitigating the impact of IS. It is important for nurses/supporters to support individuals with schizophrenia living in the community so that they have opportunities to reflect on their own experiences through their activities and to share their experiences with peers. Nurses/supporters themselves should also reflect on their own support needs. Our findings suggest that this will lead to a reduction of IS and the improvement of SOC, which will in turn promote personal recovery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 p53-Armed Oncolytic Virotherapy Improves Radiosensitivity in Soft-Tissue Sarcoma by Suppressing BCL-xL Expression 151 161 EN Tadashi Komatsubara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Joe Hasei Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshinori Omori Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhisa Sugiu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Mochizuki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Demiya Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aki Yoshida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Kunisada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/66924 Soft-tissue sarcoma (STS) is a heterogeneous group of rare tumors originating predominantly from the embryonic mesoderm. Despite the development of combined modalities including radiotherapy, STSs are often refractory to antitumor modalities, and novel strategies that improve the prognosis of STS patients are needed. We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells. Here, we demonstrate in vitro and in vivo antitumor effects of OBP-702 in combination with ionizing radiation against human STS cells (HT1080, NMS-2, SYO-1). OBP-702 synergistically promoted the antitumor effect of ionizing radiation in the STS cells by suppressing the expression of B-cell lymphoma-X large (BCL-xL) and enhancing ionizing radiation-induced apoptosis. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors’ growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 Photon-Counting Detector CT: Potential for 75% Reduction in Contrast Medium Amount: A Phantom Study 135 142 EN Fumiyo Higaki Department of Radiology, Okayama University Hospital Yusuke Morimitsu Department of Radiological Technology, Okayama University Hospital Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Hayato Saito Department of Radiological Technology, Okayama University Medical School Haruhiko Takaki Department of Radiological Technology, Okayama University Medical School Ayako Nakagoshi Department of Radiological Technology, Okayama University Medical School Maki Wada Department of Radiological Technology, Okayama University Medical School Mayu Uka Department of Radiology, Okayama University Hospital Noriaki Akagi Department of Radiological Technology, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Yusuke Matsui Department of Radiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Takao Hiraki Department of Radiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/66916 This study aimed to evaluate the potential reduction in contrast medium utilization using photon-counting detector computed tomography (PCD-CT). One PCD-CT scan (CT1) and three conventional (non-PCD-CT) CT scans (CT2-CT4) were performed using a multi-energy CT phantom that contained eight rods with different iodine concentrations (0.2, 0.5, 1, 2, 5, 10, 15, and 20 mg/ml). The CT values of the seven groups (CT1 for 40, 50, 60, and 70 keV; and CT2-4) were measured. Noise and contrast-to-noise ratio (CNR) were assessed for the eight rods at various iodine concentrations. CT2 and CT1 (40 keV) respectively required 20 mg/ml and 5 mg/ml of iodine, indicating that a comparable contrast effect could be obtained with approximately one-fourth of the contrast medium amount. The standard deviation values increased at lower energy levels irrespective of the iodine concentration. The CNR exhibited a decreasing trend with lower iodine concentrations, while it remained relatively stable across all iodine levels (40-70 keV). This study demonstrated that virtual monochromatic 40 keV images offer a similar contrast effect with a reduced contrast medium amount when compared to conventional CT systems at 120 kV. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 The Roles of Neuropeptide Y in Respiratory Disease Pathogenesis via the Airway Immune Response 95 106 EN Junko Itano Department of Hematology, Oncology and Respiratory Medicine, 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 Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuaki Miyahara Department of Allergy and Respiratory Medicine, Okayama University Hospital Review 10.18926/AMO/66912 The lungs are very complex organs, and the respiratory system performs the dual roles of repairing tissue while protecting against infection from various environmental stimuli. Persistent external irritation disrupts the immune responses of tissues and cells in the respiratory system, ultimately leading to respiratory disease. Neuropeptide Y (NPY) is a 36-amino-acid polypeptide and a neurotransmitter that regulates homeostasis. The NPY receptor is a seven-transmembrane-domain G-protein-coupled receptor with six subtypes (Y1, Y2, Y3, Y4, Y5, and Y6). Of these receptors, Y1, Y2, Y4, and Y5 are functional in humans, and Y1 plays important roles in the immune responses of many organs, including the respiratory system. NPY and the Y1 receptor have critical roles in the pathogenesis of asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis. The effects of NPY on the airway immune response and pathogenesis differ among respiratory diseases. This review focuses on the involvement of NPY in the airway immune response and pathogenesis of various respiratory diseases. 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 4 2024 2023年度における「先進病院実習」の取り組み 31 39 EN Mizuki MORITA Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tomoaki MORI Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toshiaki AIDA Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toyohiko WATANABE Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Daiji FUJII Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Nahoko HARADA Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Rei HAKAMADA Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yasuyuki YOSHIBA Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University 10.18926/interdisciplinary/66896 No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0743-7463 40 15 2024 Engineering Interconnected Open-Porous Particles via Microfluidics Using Bijel Droplets as Structural Templates 8074 8082 EN Mina Masaoka Department of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Hiroaki Ishida Department of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Takaichi Watanabe Department of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Tsutomu Ono Department of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Designing porous structures is key in materials science, particularly for separation, catalysis, and cell culture systems. Bicontinuous interfacially jammed emulsion gels represent a unique class of soft matter formed by kinetically arresting the separation of the spinodal decomposition phase, which is stabilized by colloidal particles with neutral wetting. This study introduces a microfluidic technique to create highly interconnected open-porous particles using bijel droplets stabilized with hexadecyltrimethylammonium bromide (CTAB)-modified silica particles. Monodisperse droplets comprising a hydrophobic monomer, water, ethanol, silica particles, and CTAB were initially formed in the microfluidic device. The diffusion of ethanol from these droplets into the continuous cyclohexane phase triggered spinodal decomposition within the droplets. The phase-separated structure within the droplets was stabilized by the CTAB-modified silica particles, and subsequent photopolymerization yielded microparticles with highly interconnected, open pores. Moreover, the influence of the ratio of the CTAB and silica particles, fluid composition, and microchannel direction on the final structure of the microparticles was explored. Our findings indicated that the phase-separated structure of the particles transitioned from oil-in-water to water-in-oil as the CTAB/silica ratio was increased. At intermediate CTAB/silica ratios, microparticles with bicontinuous structures were formed. Regardless of the fluid composition, the pore size of the particles increased with time after phase separation. However, this coarsening was arrested 15 s after droplet formation in the CTAB-modified silica particles, accompanied by a change in the particle shape from spherical to ellipsoidal. In situ observations of the bijel droplet formation revealed that the particle shape deformation is caused by the rolling of elastic bijel droplets at the bottom of the microchannel. As such, the channel setup was altered from horizontal to vertical to prevent the deformation of bijel droplets, resulting in spherical particles with open pores. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 3005-0731 245 1 2024 Experimental apparatus for detection of radiative decay of 229Th isomer from Th-doped CaF2 14 EN Takahiro Hiraki Research Institute for Interdisciplinary Science, Okayama University Among all the nuclei, Thorium-229 has the lowest excited level at approximately 8.3 eV. This level is an isomeric state with a long radiative lifetime. Therefore, 229Th can be excited to the isomeric state using a vacuum ultraviolet laser and is expected to have applications such as in frequency standards. Our group has been conducting experiments to excite 229Th to the isomeric state via the second excited state using the high-intensity X-ray beam available at the SPring-8 facility. To detect vacuum ultraviolet photons from the isomeric state of 229Th, a dedicated apparatus was constructed. We employed 229Th-doped CaF2 crystals as the irradiation target. Because these targets emit numerous scintillation photons due to nuclear decay and X-ray beam irradiation, detectors are required to significantly reduce these background events. To achieve this, we adopted dichroic mirrors and a photomultiplier tube for detecting scintillation photons by nuclear decay, in addition to a solar-blind photomultiplier tube for detecting decay photons from the isomeric state of 229Th. In this proceedings paper, we describe the experimental apparatus used in the beamtime in 2023. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2211-1247 43 2 2024 Stem-like progenitor and terminally differentiated TFH-like CD4+ T cell exhaustion in the tumor microenvironment 113797 EN Wenhao Zhou Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shusuke Kawashima Department of Dermatology, Chiba University Graduate School of Medicine Takamasa Ishino Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsushige Kawase Chiba Cancer Center, Research Institute Youki Ueda Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuo Yamashita KOTAI Biotechnologies, Inc. Tomofumi Watanabe Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahito Kawazu Chiba Cancer Center, Research Institute, Division of Cell Therapy Hiromichi Dansako Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yutaka Suzuki Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo Hiroyoshi Nishikawa Department of Immunology, Nagoya University Graduate School of Medicine Takashi Inozume Department of Dermatology, Chiba University Graduate School of Medicine Joji Nagasaki Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Togashi Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Immune checkpoint inhibitors exert clinical efficacy against various types of cancer through reinvigoration of exhausted CD8+ T cells that attack cancer cells directly in the tumor microenvironment (TME). Using single-cell sequencing and mouse models, we show that CXCL13, highly expressed in tumor-infiltrating exhausted CD8+ T cells, induces CD4+ follicular helper T (TFH) cell infiltration, contributing to anti-tumor immunity. Furthermore, a part of the TFH cells in the TME exhibits cytotoxicity and directly attacks major histocompatibility complex-II-expressing tumors. TFH-like cytotoxic CD4+ T cells have high LAG-3/BLIMP1 and low TCF1 expression without self-renewal ability, whereas non-cytotoxic TFH cells express low LAG-3/BLIMP1 and high TCF1 with self-renewal ability, closely resembling the relationship between terminally differentiated and stem-like progenitor exhaustion in CD8+ T cells, respectively. Our findings provide deep insights into TFH-like CD4+ T cell exhaustion with helper progenitor and cytotoxic differentiated functions, mediating anti-tumor immunity orchestrally with CD8+ T cells. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 A Case of Idiopathic Peptic Ulcer Disease Treated Effectively with Trimebutine Maleat 85 88 EN Keisuke Miyake Post graduate clinical education center, Kawasaki Medical School General Medical Center Tomohiro Tanikawa Department of General Internal Medicine 2, Kawasaki Medical School Ken Haruma Department of General Internal Medicine 2, Kawasaki Medical School Mayuko Kawada Department of General Internal Medicine 2, Kawasaki Medical School Katsunori Ishii Department of General Internal Medicine 2, Kawasaki Medical School Noriyo Urata Department of General Internal Medicine 2, Kawasaki Medical School Ken Nishino Department of General Internal Medicine 2, Kawasaki Medical School Mitsuhiko Suehiro Department of General Internal Medicine 2, Kawasaki Medical School Miwa Kawanaka Department of General Internal Medicine 2, Kawasaki Medical School Noriaki Manabe Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School Hirofumi Kawamoto Department of General Internal Medicine 2, Kawasaki Medical School Case Report 10.18926/AMO/66675 A 30-year-old man with idiopathic peptic ulcer disease (IPUD) experienced repeated recurrence of ulcerative bleeding despite treatment with lansoprazole and then vonoprazan. Further evaluation suggested that the cause of the ulcer was strong contractile movements of the antrum. This prompted the co-administration of trimebutine maleate (TM) and vonoprazan to relieve the stomach contractions. TM was effective in preventing the recurrence of ulcerative bleeding, and the patient has remained in remission for 4 years. This case highlights the potential efficacy of TM in treating IPUD and the importance of considering hypercontractility as the underlying cause in cases of IPUD. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Utility of Combined Use of Transabdominal Ultrasonography and Fecal Immunochemical Test Examinations in Ulcerative Colitis 79 83 EN Masahiro Takahara 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 Masayasu Ohmori Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiko Takeuchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Takei 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 Eriko Yasutomi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoko Igawa Department of Gastroenterology and Hepatology, 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 Junki Toyosawa Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasushi Yamasaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideaki Kinugasa Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keita Harada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideki Onishi Department of Gastroenterology and Hepatology, 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 Short Communication 10.18926/AMO/66674 This study examined the utility of the combined use of transabdominal ultrasonography (TUS) and fecal immunochemical testing (FIT) to detect mucosal inflammation, vis-a-vis the Mayo endoscopic subscore (MES), in ulcerative colitis (UC). Sixty-three UC patients who underwent TUS and FIT were retrospectively enrolled. For TUS, the colon was divided into five segments, and the bowel wall thickness was measured and evaluated. The accuracy of FIT (> 100 ng/ml) in detecting mucosal inflammation (MES>0) was 0.93, whereas that of TUS (BWT>2 mm) in each segment was 0.84-0.97. The combined use of TUS and FIT may be helpful in noninvasive treatment strategies. No potential conflict of interest relevant to this article was reported.

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

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

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Prostate Biopsy May Not Be Indicated Early after Bacillus Calmette Guérin Treatment 9 13 EN Naoki Akagi Department of Urology, Hyogo Medical University Akihiro Kanematsu Department of Urology, Hyogo Medical University Koji Shigesaka Department of Urology, Hyogo Medical University Kimihiro Shimatani Department of Urology, Hyogo Medical University Shingo Yamamoto Department of Urology, Hyogo Medical University Original Article 10.18926/AMO/66665 Bacillus Calmette-Guérin (BCG) treatment for non-muscle-invasive bladder cancer frequently causes an intraprostatic BCG granuloma. We investigated the optimal timing for a prostate biopsy after BCG treatment by retrospectively analyzing the cases of 22 patients with non-muscle-invasive bladder cancer who underwent a prostate biopsy after BCG treatment at our institute (2013-2017). Biopsies were indicated for a rising prostate-specific antigen (PSA) level, positive digital rectal examination findings, or the appearance of de novo low apparent diffusion coefficient lesions on MRI. The control group was comprised of 28 age- and PSA-matched patients. The relationships among the cancer detection rate and the patients’ PSA levels and MRI findings were analyzed. Prostate cancer was detected by biopsy in only 13.9% (3/22) of the patients in the BCG group but in 78.5% (22/28) of the control patients (p=0.0001). The three patients in the BCG group in whom prostate cancer was detected had all undergone the biopsy > 1 year after their BCG treatment. The remaining biopsies were performed within 1 year after BCG treatment and resulted in no diagnoses of prostate cancer. We suggest that performing a prostate biopsy early after BCG treatment is not informative or useful. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Role of Macrophages in Liver Fibrosis 1 8 EN Cuiming Sun Department of Pathology and Experimental Medicine, 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 Review 10.18926/AMO/66664 Liver fibrosis, which ultimately leads to liver cirrhosis and hepatocellular carcinoma, is a major health burden worldwide. The progression of liver fibrosis is the result of the wound-healing response of liver to repeated injury. Hepatic macrophages are cells with high heterogeneity and plasticity and include tissue-resident macrophages termed Kupffer cells, and recruited macrophages derived from circulating monocytes, spleen and peritoneal cavity. Studies have shown that hepatic macrophages play roles in the initiation and progression of liver fibrosis by releasing inflammatory cytokines/chemokines and pro-fibrogenic factors. Furthermore, the development of liver fibrosis has been shown to be reversible. Hepatic macrophages have been shown to alternately regulate both the regression and turnover of liver fibrosis by changing their phenotypes during the dynamic progression of liver fibrosis. In this review, we summarize the role of hepatic macrophages in the progression and regression of liver fibrosis. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1751-7362 18 1 2024 Rhizoviticin is an alphaproteobacterial tailocin that mediates biocontrol of grapevine crown gall disease 1 12 EN Tomoya Ishii Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Natsuki Tsuchida Faculty of Agriculture, Okayama University Niarsi Merry Hemelda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kirara Saito Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Jiyuan Bao Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Megumi Watanabe Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Atsushi Toyoda Department of Genomics and Evolutionary Biology, National Institute of Genetics Takehiro Matsubara Okayama University Hospital Biobank, Okayama University Hospital Mayuko Sato Mass Spectrometry and Microscopy Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science Kiminori Toyooka Mass Spectrometry and Microscopy Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science Nobuaki Ishihama Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science Ken Shirasu Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science Hidenori Matsui Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuhiro Toyoda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuki Ichinose Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tetsuya Hayashi Department of Bacteriology, Graduate School of Medical Sciences, Kyushu University Akira Kawaguchi Western Region Agricultural Research Center (WARC), National Agricultural and Food Research Organization (NARO) Yoshiteru Noutoshi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tailocins are headless phage tail structures that mediate interbacterial antagonism. Although the prototypical tailocins, R- and F-pyocins, in Pseudomonas aeruginosa, and other predominantly R-type tailocins have been studied, their presence in Alphaproteobacteria remains unexplored. Here, we report the first alphaproteobacterial F-type tailocin, named rhizoviticin, as a determinant of the biocontrol activity of Allorhizobium vitis VAR03-1 against crown gall. Rhizoviticin is encoded by a chimeric prophage genome, one providing transcriptional regulators and the other contributing to tail formation and cell lysis, but lacking head formation genes. The rhizoviticin genome retains a nearly intact early phage region containing an integrase remnant and replication-related genes critical for downstream gene transcription, suggesting an ongoing transition of this locus from a prophage to a tailocin-coding region. Rhizoviticin is responsible for the most antagonistic activity in VAR03-1 culture supernatant against pathogenic A. vitis strain, and rhizoviticin deficiency resulted in a significant reduction in the antitumorigenic activity in planta. We identified the rhizoviticin-coding locus in eight additional A. vitis strains from diverse geographical locations, highlighting a unique survival strategy of certain Rhizobiales bacteria in the rhizosphere. These findings advance our understanding of the evolutionary dynamics of tailocins and provide a scientific foundation for employing rhizoviticin-producing strains in plant disease control. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1744-683X 20 7 2024 Controlled mechanical properties of poly(ionic liquid)-based hydrophobic ion gels by the introduction of alumina nanoparticles with different shapes 1611 1619 EN Yuna Mizutani Department of Applied Chemistry, Graduate School of Natural Science, Okayama University Takaichi Watanabe Department of Applied Chemistry, Graduate School of Natural Science, Okayama University Carlos G. Lopez Department of Materials Science and Engineering, The Pennsylvania State University Tsutomu Ono Department of Applied Chemistry, Graduate School of Natural Science, Okayama University Ionic–liquid gels, also known as ion gels, have gained considerable attention due to their high ionic conductivity and CO2 absorption capacity. However, their low mechanical strength has hindered their practical applications. A potential solution to this challenge is the incorporation of particles, such as silica nanoparticles, TiO2 nanoparticles, and metal–organic frameworks (MOFs) into ion gels. Comparative studies on the effect of particles with different shapes are still in progress. This study investigated the effect of the shape of particles introduced into ion gels on their mechanical properties. Consequently, alumina/poly(ionic liquid) (PIL) double-network (DN) ion gels consisting of clustered alumina nanoparticles with various shapes (either spherical or rod-shaped) and a chemically crosslinked poly[1-ethyl-3-vinylimidazolium bis(trifluoromethanesulfonyl)imide] (PC2im-TFSI, PIL) network were prepared. The results revealed that the mechanical strengths of the alumina/PIL DN ion gels were superior to those of PIL single-network ion gels without particles. Notably, the fracture energies of the rod-shaped alumina/PIL DN ion gels were approximately 2.6 times higher than those of the spherical alumina/PIL DN ion gels. Cyclic tensile tests were performed, and the results indicate that the loading energy on the ion gel was dissipated through the fracture of the alumina network. TEM observation suggests that the variation in the mechanical strength depending on the shape can be attributed to differences in the aggregation structure of the alumina particles, thus indicating the possibility of tuning the mechanical strength of ion gels by altering not only particle kinds but its shape. 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 0003-4975 117 1 2024 Clinical Features of Patients With Second Primary Lung Cancer After Head and Neck Cancer 181 188 EN Fumiaki Takatsu Department of Thoracic Surgery, Okayama University Hospital Ken Suzawa Department of Thoracic Surgery, Okayama University Hospital Mikio Okazaki Department of Thoracic Surgery, Okayama University Hospital Kazuhiko Shien Department of Thoracic Surgery, Okayama University Hospital Hiromasa Yamamoto Department of Thoracic Surgery, Okayama University Hospital Mototsugu Watanabe Okayama University Thoracic Surgery Study Group Makio Hayama Okayama University Thoracic Surgery Study Group Tsuyoshi Ueno Okayama University Thoracic Surgery Study Group Ryujiro Sugimoto Okayama University Thoracic Surgery Study Group Yuho Maki Okayama University Thoracic Surgery Study Group Toshiya Fujiwara Okayama University Thoracic Surgery Study Group Riki Okita Okayama University Thoracic Surgery Study Group Hidetoshi Inokawa Okayama University Thoracic Surgery Study Group Hiroyuki Tao Okayama University Thoracic Surgery Study Group Yuji Hirami Okayama University Thoracic Surgery Study Group Eisuke Matsuda Okayama University Thoracic Surgery Study Group Kazuhiko Kataoka Okayama University Thoracic Surgery Study Group Motohiro Yamashita Okayama University Thoracic Surgery Study Group Yoshifumi Sano Okayama University Thoracic Surgery Study Group Motoki Matsuura Okayama University Thoracic Surgery Study Group Hisao Mizutani Okayama University Thoracic Surgery Study Group Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Background In survivors of head and neck cancer (HNC), second primary lung cancer (SPLC) often develop as a result of a common risk factor, that is, smoking. A multicenter experience was reviewed to evaluate how the history of a diagnosis of HNC affects the outcomes of patients undergoing pulmonary resection for SPLC.<br> Methods A multicenter retrospective analysis of patients hospitalized between January 2012 and December 2018 was performed. From a cohort of 4521 patients undergoing therapeutic pulmonary resection for primary non-small cell lung cancer, 100 patients with a previous history of HNC (HNC group) were identified. These patients were compared with a control group consisting of 200 patients without an HNC history from the same cohort pair-matched with operating facility, age, sex, and pathologic stage of lung cancer.<br> Results At the time of surgery for SPLC, the HNC group showed malnutrition with a lower prognostic nutritional index compared with the control group (P < .001). The HNC group was determined to have postoperative complications more frequently (P = .02). The 5-year overall survival rates in the HNC and control groups were 59.0% and 83.2%, respectively (P < .001). Statistically, HNC history, lower prognostic nutritional index, squamous cell lung cancer, and TNM stage were identified to be independently associated with poor survival.<br> Conclusions Patients with SPLC after primary HNC often present with malnutrition and are predisposed to postoperative complications and poor survival after pulmonary resection. No potential conflict of interest relevant to this article was reported.

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.

Optica Publishing Group Acta Medica Okayama 1094-4087 31 23 2023 Optical multi-context scrubbing operation on a redundant system 38529 38539 EN Kakeru Ando Graduate School of Natural Science and Technology, Okayama University Minoru Watanabe Faculty of Environmental, Life, Natural Science and Technology, Okayama University Nobuya Watanabe Faculty of Environmental, Life, Natural Science and Technology, Okayama University This paper presents a proposal of the world-first optical multi-context scrubbing operation on a redundant system that can maintain the state of a sequential circuit and the operation continuously without any interruption on a radiation-hardened optically reconfigurable gate array even after a permanent failure suddenly happens on the sequential circuit or a flip-flop by radiation. Up to now, a high-speed optical scrubbing operation has been demonstrated on a radiation-hardened optically reconfigurable gate array. In addition, a multi-context scrubbing operation based on the high-speed optical scrubbing operation has already been demonstrated. Although the multi-context scrubbing operation presents the benefit that it can treat both soft errors and permanent failures caused by radiation simultaneously, the conventional contributions have never presented how to maintain the state of a sequential circuit after a permanent failure occurs on flip-flops. Therefore, in the conventional multi-context scrubbing operation, all the operations must be restarted from the initial condition each time a permanent failure occurs on a programmable gate array. As a result, conventional multi-context scrubbing operations could not be applied for real-time systems. The proposed optical multi-context scrubbing method that can solve the issue has been experimentally evaluated on a radiation-hardened optically reconfigurable gate array. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 135 3 2023 令和４年度岡山医学会賞　がん研究奨励賞（林原賞・山田賞） 109 112 EN Kazuya Nishii Department of Hematology, Oncology Allergy and Respitatory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 3 2024 渡辺信一郎著『中国古代国家論』 308 314 EN Fuminori TSUCHIGUCHI 書評 (Book Review) 10.18926/66202 No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0960-894X 96 2023 Direct evaluation of polarity of the ligand binding pocket in retinoid X receptor using a fluorescent solvatochromic agonist 129536 EN Kizuku Miura Faculty of Pharmaceutical Sciences, Okayama University Michiko Fujihara Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaki Watanabe Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Takamura Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mayu Kawasaki Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka Shogo Nakano Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka Hiroki Kakuta Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences High selectivity of small-molecule drug candidates for their target molecule is important to minimize potential side effects. One factor that contributes to the selectivity is the internal polarity of the ligand-binding pocket (LBP) in the target molecule, but this is difficult to measure. Here, we first confirmed that the retinoid X receptor (RXR) agonist 6-(ethyl(1-isobutyl-2-oxo-4-(trifluoromethyl)-1,2-dihydroquinolin-7-yl)amino)nicotinic acid (NEt-iFQ, 1) exhibits fluorescence solvatochromism, i.e., its Stokes shift depends on the polarity of the solvent, and then we utilized this property to directly measure the internal polarity of the RXRα-LBP. The Stokes shift of 1 when bound to the RXRα-LBP corresponded to that of 1 in chloroform solution. This finding is expected to be helpful for designing RXR-selective ligands. A similar approach should be appliable to evaluate the internal polarity of the LBPs of other receptors. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Prenatal Torsion of Radial Polydactyly: A Gangrenous Mass at the Base of the Thumb 651 653 EN Daisuke Watanabe Department of Pediatrics, Faculty of Medicine, University of Yamanashi Yohei Hasebe Department of Pediatrics, Faculty of Medicine, University of Yamanashi Hiroshi Mitsui Department of Dermatology, Faculty of Medicine, University of Yamanashi Naoki Oishi Department of Pathology, Faculty of Medicine, University of Yamanashi Shin Kasai Department of Pediatrics, Faculty of Medicine, University of Yamanashi Koshi Akahane Department of Pediatrics, Faculty of Medicine, University of Yamanashi Satoru Kojika Department of Pediatrics, Faculty of Medicine, University of Yamanashi Takeshi Inukai Department of Pediatrics, Faculty of Medicine, University of Yamanashi Case Report 10.18926/AMO/66158 A patient was born with a mass at the base of the thumb approximately 1.5 cm in diameter on the radial side of the fingers. The mass had globular swelling filled with hemorrhagic fluid and was dark red. X-rays and histology of the excised specimen suggested the diagnosis of gangrene and torsion of polydactyly. Prenatal torsion of polydactyly is not a common occurrence; moreover, prenatal torsion of polydactyly has only been found in ulnar polydactyly. Our case is a novel case of radial polydactyly that was gangrenous at birth owing to prenatal torsion. Diagnosing such a mass at the base of the thumb is important. 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.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Survey of Osteoarthritis of the Shoulder in Patients who Underwent Knee Arthroplasty for Knee Osteoarthritis 613 618 EN Yoshiaki Miyake Department of Bone and Joint Surgery, Kawasaki Medical School Yoshifumi Namba Department of Bone and Joint Surgery, Kawasaki Medical School Shigeru Mitani Department of Bone and Joint Surgery, Kawasaki Medical School Norifumi Umehara Department of Bone and Joint Surgery, Kawasaki Medical School Toyohiro Kawamoto Department of Bone and Joint Surgery, Kawasaki Medical School Shuro Furuichi Department of Bone and Joint Surgery, Kawasaki Medical School Original Article 10.18926/AMO/66153 The relationship between osteoarthritis (OA) of the lower extremity and shoulder OA has not been established. This study evaluated the prevalence of shoulder OA in patients with knee OA. We collected contrast-enhanced computed tomography (CECT) images of the shoulder joints of 105 patients with knee OA that were taken 1 week after they underwent primary knee arthroplasty to check for venous thromboembolism (VTE). The images were compared with CECT images of 110 control-group patients that were taken for the purpose of differentiating VTE. Shoulder OA was present in a significantly higher percentage of patients with knee arthroplasty than controls (29% versus 15%), and the difference was particularly pronounced in patients in their 70s (33%) compared to age-matched controls (11%). Patients with knee OA often use arm support to stand up or walk due to knee joint pain and muscle weakness, which places the weight-bearing shoulder at risk of developing OA. No potential conflict of interest relevant to this article was reported.

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

Acta Medica Okayama 2023 権威主義的環境主義下におけるガバナンスの構造―ベトナム南部のマングローブ・エビ養殖地域を事例に― EN Hiroki WATANABE Graduate School of Environmental and Life Science, Okayama University No potential conflict of interest relevant to this article was reported.

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

Acta Medica Okayama 2023 Prevalence of transthyretin amyloidosis among heart failure patients with preserved ejection fraction in Japan EN Takanori NAITO Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Prevalence and Treatment of Arrhythmias in Patients With Transthyretin and Light-Chain Cardiac Amyloidosis EN Masakazu MIYAMOTO Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 PD-1 blockade augments CD8+ T cell dependent antitumor immunity triggered by Ad-SGE-REIC in Egfr-mutant lung cancer EN Takamasa NAKASUKA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2213-0071 38 2022 Massive hemoptysis in a post-operative patient with recurrent lung cancer successfully treated by the combination therapy of Endobronchial Watanabe Spigot and bronchial artery embolization 101669 EN Masataka Taoka Department of Allergy and Respiratory Medicine, Okayama University Hospital Go Makimoto Department of Allergy and Respiratory Medicine, Okayama University Hospital Noriyuki Umakoshi Department of Radiology, Okayama University Hospital Kiichiro Ninomiya Department of Allergy and Respiratory Medicine, Okayama University Hospital Hisao Higo Department of Allergy and Respiratory Medicine, Okayama University Hospital Yuka Kato Center for Innovative Clinical Medicine, Okayama University Hospital Masanori Fujii Department of Allergy and Respiratory Medicine, Okayama University Hospital Toshio Kubo Center for Clinical Oncology, Okayama University Hospital Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Kadoaki Ohashi Department of Allergy and Respiratory Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Masahiro Tabata Center for Clinical Oncology, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital A 76-year-old woman who was treated with lorlatinib for postoperative recurrent anaplastic lymphoma kinase-positive lung adenocarcinoma visited our hospital with massive hemoptysis. Chest computed tomography showed massive bleeding from the right upper lobe; however, the cause of bleeding was unclear. After bronchial artery embolization (BAE), bronchial occlusion was performed using an Endobronchial Watanabe Spigot (EWS) that was easily placed because BAE had reduced the bleeding volume. Treatment with BAE alone was inadequate; however, additional therapy with EWS after BAE successfully controlled the massive hemoptysis, especially in this patient who underwent lobectomy to prevent respiratory dysfunction. No potential conflict of interest relevant to this article was reported.

nature portfolio Acta Medica Okayama 2045-2322 13 1 2023 Photo-dependent cytosolic delivery of shRNA into a single blastomere in a mouse embryo 13050 EN Yuka Ikawa Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takuya Wakai Department of Animal Science, Graduate of Environmental and Life Science, Okayama University Hiroaki Funahashi Department of Animal Science, Graduate of Environmental and Life Science, Okayama University Tet Htut Soe Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kazunori Watanabe Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takashi Ohtsuki Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Single-cell-specific delivery of small RNAs, such as short hairpin RNA (shRNA) and small noncoding RNAs, allows us to elucidate the roles of specific upregulation of RNA expression and RNAi-mediated gene suppression in early embryo development. The photoinduced cytosolic dispersion of RNA (PCDR) method that we previously reported can introduce small RNAs into the cytosol of photoirradiated cells and enable RNA delivery into a single-cell in a spatiotemporally specific manner. However, the PCDR method has only been applied to planer cultured cells and not to embryos. This study demonstrated that the PCDR method can be utilized for photo-dependent cytosolic shRNA delivery into a single blastomere and for single blastomere-specific RNA interference in mouse embryos. Our results indicate that PCDR is a promising approach for studying the developmental process of early embryogenesis. No potential conflict of interest relevant to this article was reported.

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

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

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Participation in the Setouchi Triennale and the Health of Residents in Naoshima: A Cross-Sectional Study 491 497 EN Hiroshi Habu Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soshi Takao Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chikara Miyaji Department of Epidemiology, 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 Ken Aoo Graduate School of Humanities and Social Sciences, Okayama University Yosuke Nishita Graduate School of Humanities and Social Sciences, Okayama University Masao Tsuri Faculty of Economics, Musashi University Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65971 Arts festivals have become increasingly popular in various parts of Japan in recent years. The purpose of this study was to investigate the relationships between arts festival activities participation at the Setouchi Triennale and the health of residents in the town of Naoshima. This was a cross-sectional study. Questionnaires were distributed to all residents of Naoshima who were 20 years old or older (n=2,588). We analyzed responses from 708 people. The associations between arts festival activities participation and health (measured by self-rated health) were analyzed using logistic regression analysis as the primary outcome. Kessler’s psychological distress scale scores were also analyzed in the same manner as the primary outcome. The participating group had an adjusted odds ratio of 1.86 (95% confidence interval: 1.03-3.33) for higher self-rated health compared with those who did not participate. Kessler’s psychological distress scale results showed that the participating group had an adjusted odds ratio of 3.23 (95% confidence interval: 1.19-8.81) for lower psychological distress compared with those who did not participate. In conclusion, arts festival activities participation was associated with higher self-rated health and lower psychological distress. However, caution must be taken in regard to generalizability and causality when interpreting these results. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 An Assessment Rubric for a Resident Training Program in Surgery: A Single-Institution Experience 451 460 EN Atsushi Okita Department of Surgery, Okayama City Hospital Kazunori Tsukuda Department of Surgery, Okayama City Hospital Hideo Ino Center for Education in Medicine and Health Science, Okayama University Ema Mitsui Department of Surgery, Okayama City Hospital Nanami Ikeya Department of Surgery, Okayama City Hospital Sumiharu Yamamoto Department of Surgery, Okayama City Hospital Nobuji Yokoyama Department of Surgery, Okayama City Hospital Aubra Bulin Discovery Program for Global Learners, Okayama University Original Article 10.18926/AMO/65967 Using a Collaborative Action Research model, our research team established a one-month clinical resident training program for first- and second-year clinical residents. We created and implemented an assessment rubric to assess the residents’ progress toward independent practice in surgery, and thereby, to evaluate the program itself. The program included training in three areas: basic techniques and procedures in the operating room, surgical ward management, and academic activities. The rubric measured the residents’ performance according to three achievement levels: Level 1 (demonstration), Level 2 (active help) and Level 3 (passive help). The program and rubric implementation began in June 2019 and continued until March 2020, when the program outcomes and shortcomings were analyzed. Among nineteen clinical residents, a total of nine clinical residents participated in the study. Most participants reached achievement Level 3 for their performance of basic techniques in the operating room. Finally, we discussed ideas for improvement and drafted plans for an improved rubric to complete the action research cycle. Our research team found the rubric to be a useful tool in evaluating the status of the new clinical resident training program. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 114 11 2023 Efficacy of gilteritinib in comparison with alectinib for the treatment of ALK-rearranged non-small cell lung cancer 4343 4354 EN Chihiro Ando Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Tatsuya Nishi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ayako Morita Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naofumi Hara Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenji Takada Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takamasa Nakasuka Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiromi Watanabe Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hirohisa Kano Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Nishii Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Go Makimoto Center for Clinical Oncology, Okayama University Hospital Takumi Kondo Department of Hematology and Oncology, Okayama University Hospital Kiichiro Ninomiya Department of Allergy and Respiratory Medicine, Okayama University Hospital Masanori Fujii Department of Allergy and Respiratory Medicine, Okayama University Hospital Toshio Kubo Department of Allergy and Respiratory Medicine, Okayama University Hospital Kadoaki Ohashi Department of Allergy and Respiratory Medicine, Okayama University Hospital Ken-Ichi Matsuoka Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Masahiro Tabata Center for Clinical Oncology, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Gilteritinib is a multitarget tyrosine kinase inhibitor (TKI), approved for the treatment of FLT3-mutant acute myeloid leukemia, with a broad range of activity against several tyrosine kinases including anaplastic lymphoma kinase (ALK). This study investigated the efficacy of gilteritinib against ALK-rearranged non-small cell lung cancers (NSCLC). To this end, we assessed the effects of gilteritinib on cell proliferation, apoptosis, and acquired resistance responses in several ALK-rearranged NSCLC cell lines and mouse xenograft tumor models and compared its efficacy to alectinib, a standard ALK inhibitor. Gilteritinib was significantly more potent than alectinib, as it inhibited cell proliferation at a lower dose, with complete attenuation of growth observed in several ALK-rearranged NSCLC cell lines and no development of drug tolerance. Immunoblotting showed that gilteritinib strongly suppressed phosphorylated ALK and its downstream effectors, as well as mesenchymal-epithelial transition factor (MET) signaling. By comparison, MET signaling was enhanced in alectinib-treated cells. Furthermore, gilteritinib was found to more effectively abolish growth of ALK-rearranged NSCLC xenograft tumors, many of which completely receded. Interleukin-15 (IL-15) mRNA levels were elevated in gilteritinib-treated cells, together with a concomitant increase in the infiltration of tumors by natural killer (NK) cells, as assessed by immunohistochemistry. This suggests that IL-15 production along with NK cell infiltration may constitute components of the gilteritinib-mediated antitumor responses in ALK-rearranged NSCLCs. In conclusion, gilteritinib demonstrated significantly improved antitumor efficacy compared with alectinib against ALK-rearranged NSCLC cells, which can warrant its candidacy for use in anticancer regimens, after further examination in clinical trial settings. No potential conflict of interest relevant to this article was reported.

VM Media SP. zo.o VM Group SK Acta Medica Okayama 1898-018X 29 3 2021 The number of circulating CD34-positive cells is an independent predictor of coronary artery calcification progression: Sub-analysis of a prospective multicenter study 423 431 EN Keishi Ichikawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Kazuhiro Osawa Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital Takashi Miki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Kunihisa Kohno Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Yasushi Koyama Department of Cardiology, Sakurabashi Watanabe Hospital Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Background: Decreases in circulating CD34-positive cells are associated with increases in cardiovascular events. We investigated the association between the number of CD34-positive cells and the progression of coronary artery calcification (CAC), a marker of atherosclerosis, in patients with hypercholesteremia under statin therapy in a sub-analysis of a multicenter study.<br> Methods: In the principal study, patients with CAC scores of 1–999 were treated with pitavastatin. Measurement of CAC by non-enhanced computed tomography and a blood test were performed at baseline and at 1-year follow-up. Patients were divided into two groups: CAC progression (change in CAC score > 0) and non-progression. The number of circulating CD34-positive cells was counted using flow cytometry.<br> Results: A total of 156 patients (mean age 67 years, 55% men) were included in this sub-analysis. CD34 positive cell numbers at baseline as a continuous variable was inversely correlated with annual change in the log-transformed CAC score (r = –0.19, p = 0.02). When patients were divided into high and low CD34 groups based on the median value of 0.8 cells/μL, the adjusted change in CAC score in the low-CD34 group was significantly greater than that in the high-CD34 group (54.2% vs. 20.8%, respectively, p = 0.04). In multiple logistic analysis, a low CD34-positive cell number was an independent predictor of CAC progression, with an odds ratio of 2.88 (95% confidence interval 1.28–6.49, p = 0.01).<br> Conclusions: Low numbers of CD34-positive cells are associated with CAC progression in patients with hypercholesterolemia under statin therapy. The number of CD34-positive cells may help to identify patients at increased cardiovascular risk. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 Association of Tumor Necrosis Factor-Alpha with Psychopathology in Patients with Schizophrenia 395 405 EN Marko Pavlovic University Hospital Center Mostar, University of Mostar Dragan Babic University Hospital Center Mostar, University of Mostar Pejana Rastovic University Hospital Center Mostar, University of Mostar Jurica Arapovic University Hospital Center Mostar, University of Mostar Marko Martinac Health Care Center Mostar, University of Mostar Sanja Jakovac University Hospital Center Mostar, University of Mostar Romana Barbaric University Hospital Center Mostar, University of Mostar Original Article 10.18926/AMO/65750 We investigated the relationship between serum tumor necrosis factor-alpha (TNF-α) levels and psychopathological symptoms, clinical and socio-demographic characteristics and antipsychotic therapy in individuals with schizophrenia. TNF-α levels were measured in 90 patients with schizophrenia and 90 healthy controls matched by age, gender, smoking status, and body mass index. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of psychopathology in patients. No significant differences in TNF-α levels were detected between the patients and controls (p=0.736). TNF-α levels were not correlated with total, positive, negative, general, or composite PANSS scores (all p>0.05). A significant negative correlation was observed between TNF-α levels and the PANSS cognitive factor (ρ=−0.222, p=0.035). A hierarchical regression analysis identified the cognitive factor as a significant predictor of the TNF-α level (beta=−0.258, t=−2.257, p=0.027). There were no significant differences in TNF-α levels among patients treated with different types of antipsychotics (p=0.596). TNF-α levels correlated positively with the age of onset (ρ=0.233, p=0.027) and negatively with illness duration (ρ=−0.247, p=0.019) and antipsychotic treatment duration (ρ=−0.256, p=0.015). These results indicate that TNF-α may be involved in cognitive impairment in schizophrenia, and would be a potential clinical-state marker in schizophrenia. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 Association between Radon Hot Spring Bathing and Health Conditions: A Cross-Sectional Study in Misasa, Japan 387 394 EN Takahiro Kataoka Department of Radiological Technology, Okayama University Graduate School of Health Sciences Hiroshi Habu Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayumi Tanaka Department of Radiological Technology, Okayama University Graduate School of Health Sciences Shota Naoe Department of Radiological Technology, Okayama University Graduate School of Health Sciences Kaito Murakami Department of Radiological Technology, Okayama University Graduate School of Health Sciences Yuki Fujimoto Department of Radiological Technology, Okayama University Graduate School of Health Sciences Ryohei Yukimine Department of Radiological Technology, Okayama University Graduate School of Health Sciences Soshi Takao Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumihiro Mitsunobu Department of Longevity and Social Medicine (Geriatrics), 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 Kiyonori Yamaoka Department of Radiological Technology, Okayama University Graduate School of Health Sciences Original Article 10.18926/AMO/65749 No epidemiological studies have examined the health effects of daily bathing in radon hot springs. In this cross-sectional study, we investigated the associations between radon hot spring bathing and health conditions. The target population was 5,250 adults ≥ 20 years old in the town of Misasa, Japan. We collected information about the participants’ bathing habits and alleviation of a variety of disease symptoms, and their self-rated health (SRH). Unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CI) were calculated. In both the adjusted and unadjusted models of hypertension, significant associations between the > 1×/week hot spring bathing and the alleviation of hypertension symptoms were observed compared to the group whose hot spring bathing was <1×/week: adjusted model, OR 5.40 (95%CI: 1.98-14.74); unadjusted model, 3.67 (1.50-8.99) and for gastroenteritis: adjusted model, 9.18 (1.15-72.96); unadjusted model, 7.62 (1.59-36.49). Compared to the no-bathing group, higher SRH was significantly associated with both bathing < 1×/week: unadjusted model, 2.27 (1.53-3.37) and > 1×/week: adjusted model, 1.91 (1.15-3.19). These findings suggest that bathing in radon hot springs is associated with higher SRH and the alleviation of hypertension and gastroenteritis. 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.

Springer Science and Business Media LLC Acta Medica Okayama 1345-2630 89 4 2023 Positive chemotaxis to plant apoplastic fluids of Pseudomonas syringae pv. tabaci 6605 and metabolome analysis 219 223 EN Yuta Watanabe The Graduate School of Environmental and Life Science, Okayama University Stephany Angelia Tumewu The Graduate School of Environmental and Life Science, Okayama University Hajime Yamada Faculty of Agriculture, Okayama University Hidenori Matsui The Graduate School of Environmental and Life Science, Okayama University Mikihiro Yamamoto The Graduate School of Environmental and Life Science, Okayama University Yoshiteru Noutoshi The Graduate School of Environmental and Life Science, Okayama University Kazuhiro Toyoda The Graduate School of Environmental and Life Science, Okayama University Yuki Ichinose The Graduate School of Environmental and Life Science, Okayama University Pseudomonas syringae pv. tabaci 6605 (Pta6605) is a causal agent of wildfire disease in host tobacco plants. Although chemotaxis has been shown to be necessary for Pta6605 in tobacco infection, the chemoattractants at the site of infection are unclear. Pta6605 was attracted to the apoplastic fluid from not only host tobacco leaves but also non-host plant leaves, indicating that Pta6605 is attracted to common plant metabolites. Metabolome analysis of apoplastic fluid from tobacco leaves revealed that amino acids including γ-aminobutyric acid and organic acids are abundant, suggesting that these compounds are potential chemoattractants. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1932-7447 127 28 2023 Lithium-Ion Dynamics in Sulfolane-Based Highly Concentrated Electrolytes 13837 13845 EN Shuhei Ikeda Department of Materials Chemistry, Nagoya University Seiji Tsuzuki Advanced Chemical Energy Research Centre (ACERC), Institute of Advanced Sciences, Yokohama National University Taku Sudoh Department of Chemistry and Life Science, Yokohama National University Keisuke Shigenobu Research Institute for Interdisciplinary Science, Okayama University Kazuhide Ueno Advanced Chemical Energy Research Centre (ACERC), Institute of Advanced Sciences, Yokohama National University Kaoru Dokko Advanced Chemical Energy Research Centre (ACERC), Institute of Advanced Sciences, Yokohama National University Masayoshi Watanabe Advanced Chemical Energy Research Centre (ACERC), Institute of Advanced Sciences, Yokohama National University Wataru Shinoda Research Institute for Interdisciplinary Science, Okayama University, Here, we report the use of molecular dynamics simulations with a polarizable force field to investigate Li-ion dynamics in sulfolane (SL)-based electrolytes. In SL-based highly concentrated electrolytes (HCEs) (e.g., SL/Li = 2:1), Li displays faster translational motion than other components, which should be related to the structural and dynamical properties of SL. In HCEs, a transient conduction network that penetrated the simulation system was always observed. Rapid (<1 ns) Li-ion hopping between adjacent coordination sites was observed throughout the network. Additionally, SLs rotated in the same timeframe without disrupting the conduction network. This rotation is believed to promote the hopping diffusion in the network. This was followed by a rotational relaxation of the SL dipole axis around the non-polar cyclohydrocarbon segment of SL (∼3.3 ns), which involves a reorganization of the network structure and an enhancement of the translational motion of the coordinating Li ions. The observed lifetime of Li–SL coordination was longer (>11 ns). Hence, it was concluded that the faster Li translational motion was obtained due to the faster rotational relaxation time of SL rather than the lifetime of Li–SL binding. The faster rotation of SL is related to its amphiphilic molecular structure with compact non-polar segments. Transport properties, such as the Onsager transport coefficients, ionic conductivity, and transference number under anion-blocking conditions, were also analyzed to characterize the features of the SL-based electrolyte. No potential conflict of interest relevant to this article was reported.

Proceedings of the National Academy of Sciences Acta Medica Okayama 0027-8424 119 43 2022 Structures and mechanisms of actin ATP hydrolysis e2122641119 EN Yusuke Kanematsu Graduate School of Information Sciences, Hiroshima City University Akihiro Narita Structural Biology Research Center, Graduate School of Science, Nagoya University Toshiro Oda Faculty of Health and Welfare, Tokai Gakuin University Ryotaro Koike Graduate School of Informatics, Nagoya University Motonori Ota Graduate School of Informatics, Nagoya University Yu Takano Graduate School of Information Sciences, Hiroshima City University Kei Moritsugu Graduate School of Medical Life Science, Yokohama City University Ikuko Fujiwara Graduate School of Science, Osaka City University Kotaro Tanaka Structural Biology Research Center, Graduate School of Science, Nagoya University Hideyuki Komatsu Department of Bioscience and Bioinformatics, Graduate School of Computer Science and Systems Engineering, Kyushu Institute of Technology Takayuki Nagae Synchrotron Radiation Research Center, Nagoya University Nobuhisa Watanabe Synchrotron Radiation Research Center, Nagoya University Mitsusada Iwasa Graduate School of Informatics, Nagoya University Yuichiro Maéda Research Institute for Interdisciplinary Science, Okayama University Shuichi Takeda Research Institute for Interdisciplinary Science, Okayama University The major cytoskeleton protein actin undergoes cyclic transitions between the monomeric G-form and the filamentous F-form, which drive organelle transport and cell motility. This mechanical work is driven by the ATPase activity at the catalytic site in the F-form. For deeper understanding of the actin cellular functions, the reaction mechanism must be elucidated. Here, we show that a single actin molecule is trapped in the F-form by fragmin domain-1 binding and present their crystal structures in the ATP analog-, ADP-Pi-, and ADP-bound forms, at 1.15-Å resolutions. The G-to-F conformational transition shifts the side chains of Gln137 and His161, which relocate four water molecules including W1 (attacking water) and W2 (helping water) to facilitate the hydrolysis. By applying quantum mechanics/molecular mechanics calculations to the structures, we have revealed a consistent and comprehensive reaction path of ATP hydrolysis by the F-form actin. The reaction path consists of four steps: 1) W1 and W2 rotations; 2) PG–O3B bond cleavage; 3) four concomitant events: W1–PO3− formation, OH− and proton cleavage, nucleophilic attack by the OH− against PG, and the abstracted proton transfer; and 4) proton relocation that stabilizes the ADP-Pi–bound F-form actin. The mechanism explains the slow rate of ATP hydrolysis by actin and the irreversibility of the hydrolysis reaction. While the catalytic strategy of actin ATP hydrolysis is essentially the same as those of motor proteins like myosin, the process after the hydrolysis is distinct and discussed in terms of Pi release, F-form destabilization, and global conformational changes. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 18794068 14 5 2023 Significance of the comprehensive geriatric assessment in the administration of chemotherapy to older adults with cancer: Recommendations by the Japanese Geriatric Oncology Guideline Committee 101485 EN Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Daisuke Inoue Department of Obstetrics and Gynecology, University of Fukui Ken Sugimoto Department of General Geriatric Medicine, Kawasaki Medical School Chie Tanaka Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine Keiko Murofushi Division of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Toru Okuyama Department of Psychiatry / Palliative Care Center, Nagoya City University West Medical Center Shigeaki Watanuki National Center for Global Health and Medicine, National College of Nursing Chiyo K. Imamura Advanced Cancer Translational Research Institute, Showa University Daisuke Sakai Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine Naomi Sakurai Cancer Solutions Co.,Ltd Kiyotaka Watanabe Division of Medical Oncology, Department of Medicine, School of Medicine, Teikyo University Kazuo Tamura NPO Clinical Hematology/Oncology Treatment Study Group Toshiaki Saeki Breast Oncology Service, Saitama Medical University International Medical Center Hiroshi Ishiguro Breast Oncology Service, Saitama Medical University International Medical Center Introduction: The number of older patients with cancer is expected to continue to increase owing to the aging population. Recently, the usefulness of geriatric assessment (GA) conducted by multiple staff members from different medical backgrounds has been reported; however, a consensus on the effectiveness of GA has not yet been achieved.<br> Materials and Methods: We, as the Japanese Geriatric Oncology Guideline Committee for elderly patients with cancer, conducted a literature search of randomized controlled trials published before August 2021 that used GA or comprehensive GA (CGA) as an intervention for patients with cancer undergoing chemotherapy. As the key outcomes for answering the clinical question, we focused on survival benefit, adverse events, and quality of life (QOL). After a systematic review of these studies, the expert panel member developed recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.<br> Results: For older patients with cancer, GA or CGA is suggested during or before chemotherapy (weakly recommended). Chemotherapy-induced adverse events were significantly reduced by GA/CGA interventions without any adverse effects on survival. Health-related QOL tended to improve with the GA/CGA interventions.<br> Discussion: Although, in our opinion, GA/CGA does require time and resources, it poses no harm patients. Therefore, we suggest expanding the human resources and educating skills of medical providers for clinical implementation of GA/CGA. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 77 3 2023 Endobronchial Metastasis with Bloody Sputum 20 Years after Complete Resection of type A Non-Invasive Thymoma 331 334 EN Mototsugu Watanabe Department of Thoracic Surgery, Okayama University Hospital Hiromasa Yamamoto Department of Thoracic Surgery, Okayama University Hospital Kentaroh Miyoshi Department of Thoracic Surgery, Okayama University Hospital Seiichiro Sugimoto Department of Thoracic Surgery, Okayama University Hospital Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Case Report 10.18926/AMO/65503 Masaoka stage I type A thymomas rarely recur. We report the case of an 82-year-old man who developed endobronchial metastasis after thymothymectomy for Masaoka stage I type A thymoma. Twenty years after surgery, the patient developed bloody sputum, and chest computed tomography revealed a neoplasm obstructing the right upper lobe bronchus of the lung with enlarged mediastinal lymph nodes. He underwent right upper lobectomy and mediastinal lymph node dissection. Although preoperative pathological diagnosis was squamous cell carcinoma of the lung, postoperative histopathology revealed endobronchial metastasis of the thymoma. Nine years later, at age 89, the patient is alive and well. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 77 3 2023 Impact of Immediate Breast Reconstruction on Survival of Breast Cancer Patients: A Single-Center Observational Study 281 290 EN Yuko Mukai Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naruto Taira Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital Yukiko Kajiwara Department of Breast Surgery, Hiroshima Citizens Hospital Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Yohei Kitaguchi Department of Plastic and Reconstructive Surgery, Okayama University Hospital Miho Saiga Department of Plastic and Reconstructive Surgery, Okayama University Hospital Satoko Watanabe Department of Plastic and Reconstructive Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyoshi Doihara Department of Breast and Endocrine Surgery, Okayama University Hospital Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65493 Although immediate breast reconstruction following mastectomy has become increasingly common, its oncological safety has been debated. We enrolled patients with breast cancer who underwent surgery at Okayama University Hospital between 2007 and 2013. The primary outcome was relapse-free survival (RFS). Secondary outcomes were overall survival and the duration from the surgery to the initiation of adjuvant chemotherapy. We divided into immediate breast reconstruction, mastectomy alone, and breast conservative surgery groups. Outcomes were compared using Cox’s regression analysis. A total of 614 patients were included (reconstruction: 125, mastectomy: 128, breast conservative surgery: 361). The median follow-up duration was 79.0±31.9 months. The immediate-reconstruction patients were younger, had more lymph node metastases, and more often received postoperative chemotherapy. The RFS was better after the breast conservative surgery compared to after reconstruction (hazard ratio 0.33, 95% confidence interval: 0.144-0.763). The proportion of local recurrence was highest in the reconstruction group. No patients in the reconstruction group underwent postoperative radiation therapy. However, reconstruction did not affect overall survival or the time to the initiation of adjuvant chemotherapy. Surgeons should explain the risks of breast reconstruction to their patients preoperatively. Careful long-term follow-up is required after such procedures. 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 3 2023 2022 年度における「先進病院実習」の取り組み 75 82 EN Mizuki MORITA Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Naoki KANAYAMA Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toshiaki AIDA Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toyohiko WATANABE Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Noboru YAMASHITA Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Rei HAKAMADA Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yasuyuki YOSHIBA Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University 10.18926/interdisciplinary/65468 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. <br> 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. <br> 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). <br> 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.

Acta Medica Okayama 2023 Simultaneous assay of urine sepiapterin and creatinine in patients with sepiapterin reductase deficiency EN Yuki HYODO Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Toll-like receptor 4 promotes bladder cancer progression upon S100A8/A9 binding, which requires TIRAP-mediated TPL2 activation EN ACOSTA GONZALEZ HERIK RODRIGO Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Incidence, Factors, and Prognostic Impact of Re-Exploration for Bleeding After Continuous-Flow Left Ventricular Assist Device Implantation- A Japanese Single-Center Study - EN Keiichiro IWASAKI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 CD8+ T-cell Responses Are Boosted by Dual PD-1/VEGFR2 Blockade after EGFR Inhibition in Egfr-Mutant Lung Cancer EN Kazuya NISHII Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Taylor and Francis Acta Medica Okayama 1343-943X 2023 Biomass estimation of World rice (Oryza sativa L.) core collection based on the convolutional neural network and digital images of canopy EN Kota Nakajima Graduate School of Agriculture, Kyoto University Yu Tanaka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Keisuke Katsura United Graduate School of Agriculture Science, Tokyo University of Agriculture and Technology Tomoaki Yamaguchi United Graduate School of Agriculture Science, Tokyo University of Agriculture and Technology Tomoya Watanabe Independent researcher Tatsuhiko Shiraiwa Graduate School of Agriculture, Kyoto University Above-ground biomass (AGB) is an important indicator of crop productivity. Destructive measurements of AGB incur huge costs, and most non-destructive estimations cannot be applied to diverse cultivars having different canopy architectures. This insufficient access to AGB data has potentially limited improvements in crop productivity. Recently, a deep learning technique called convolutional neural network (CNN) has been applied to estimate crop AGB due to its high capacity for digital image recognition. However, the versatility of the CNN-based AGB estimation for diverse cultivars is still unclear. We established and evaluated a CNN-based estimation method for rice AGB using digital images with 59 diverse cultivars which were mostly in World Rice Core Collection. Across two years at two locations, we took 12,183 images of 59 cultivars with commercial digital cameras and manually obtained their corresponding AGB. The CNN model was established by using 28 cultivars and showed high accuracy (R-2 = 0.95) to the test dataset. We further evaluated the performance of the CNN model by using 31 cultivars, which were not in the model establishment. The CNN model successfully estimated AGB when the observed AGB was lesser than 924 g m(-2) (R-2 = 0.87), whereas it underestimated AGB when the observed AGB was greater than 924 g m(-2) (R-2 = 0.02). This underestimation might be improved by adding training data with a greater AGB in further study. The present study indicates that this CNN-based estimation method is highly versatile and could be a practical tool for monitoring crop AGB in diverse cultivars. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0169-5002 178 2023 PD-1 blockade augments CD8+ T cell dependent antitumor immunity triggered by Ad-SGE-REIC in Egfr-mutant lung cancer 1 10 EN Takamasa Nakasuka Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Kazuya Nishii Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuko Hirabae Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sachi Okawa Department of Hematology, Oncology and Respiratory Medicine, 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 Kenji Takada Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chihiro Ando Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromi Watanabe Department of Respiratory Medicine, Okayama University Hospital Go Makimoto Department of Respiratory Medicine, Okayama University Hospital Kiichiro Ninomiya Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine Masanori Fujii Department of Respiratory Medicine, Okayama University Hospital Toshio Kubo Center for Clinical Oncology, Okayama University Hospital Eiki Ichihara Department of Respiratory Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Masahiro Tabata Center for Clinical Oncology, Okayama University Hospital Hiromi Kumon Innovation Center Okayama for Nanobio-targeted Therapy, Okayama University Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Objectives: No immunotherapeutic protocol has yet been established in never-smoking patients with lung cancer harboring driver oncogenic mutations, such as epidermal growth factor receptor (EGFR) mutations. The immunostimulatory effect of Ad-REIC, a genetically engineered adenovirus vector expressing a tumor suppressor gene, reduced expression in immortalized cells (REIC), has been investigated in clinical trials for various solid tumors. However, the immunostimulatory effect of the Ad-REIC in EGFR-mutant lung cancer with a non-inflamed tumor microenvironment (TME) has not been explored.<br> Materials and methods: We used a syngeneic mouse model developed by transplanting Egfr-mutant lung cancer cells into single or double flanks of C57BL/6J mice. Ad-SGE-REIC, a 2nd-generation vector with an enhancer sequence, was injected only into the tumors from one flank, and its antitumor effects were assessed. Tumor-infiltrating cells were evaluated using immunohistochemistry or flow cytometry. The synergistic effects of Ad-SGE-REIC and PD-1 blockade were also examined.<br> Results: Injection of Ad-SGE-REIC into one side of the tumor induced not only a local antitumor effect but also a bystander abscopal effect in the non-injected tumor, located on the other flank. The number of PD-1+CD8+ T cells increased in both injected and non-injected tumors. PD-1 blockade augmented the local and abscopal antitumor effects of Ad-SGE-REIC by increasing the number of CD8+ T cells in the TME of Egfr-mutant tumors. Depletion of CD8+ cells reverted the antitumor effect, suggesting they contribute to antitumor immunity.<br> Conclusion: Ad-SGE-REIC induced systemic antitumor immunity by modifying the TME status from non-inflamed to inflamed, with infiltration of CD8+ T cells. Additionally, in Egfr-mutant lung cancer, this effect was enhanced by PD-1 blockade. These findings pave the way to establish a novel combined immunotherapy strategy with Ad-SGE-REIC and anti-PD-1 antibody for lung cancer with a non-inflamed TME. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry Acta Medica Okayama 1744-683X 19 15 2023 Toughening of poly(ionic liquid)-based ion gels with cellulose nanofibers as a sacrificial network 2745 2754 EN Takaichi Watanabe Department of Applied Chemistry, Graduate School of Natural Science, Okayama University Emiho Oe Department of Applied Chemistry, Graduate School of Natural Science, Okayama University Yuna Mizutani Department of Applied Chemistry, Graduate School of Natural Science, Okayama University Tsutomu Ono Department of Applied Chemistry, Graduate School of Natural Science, Okayama University Ion gels have the potential to be used in a broad range of applications, such as in carbon dioxide separation membranes and soft electronics. However, their low mechanical strength limits their practical applications. In this study, we developed double-network (DN) ion gels composed of TEMPO-oxidized cellulose nanofibers with hydrophobic groups (TOCNF) and cross-linked poly[1-ethyl-3-vinylimidazolium bis(trifluoromethanesulfonyl)imide] (PC2im-TFSI) networks. The mechanical strength of the gel increased as the amount of TOCNF in the gels increased up to 6 wt%. Moreover, the fracture energy of the DN ion gels with 6 wt% TOCNF was found to be 19 times higher than that of the PC2im-TFSI single network (SN) ion gels. Cyclic stress-strain measurements of the DN gels showed that the loading energy on the gels dissipates owing to the destruction of the physically cross-linked TOCNF network in the gels. The DN ion gels also exhibited a high decomposition temperature of approximately 400 degrees C because of the thermal stability of all components. Additionally, the fracture energy of the TOCNF/poly(ionic liquid) (PIL) DN ion gel was two times higher than that of the silica nanoparticles/PIL DN ion gel developed in our previous study [Watanabe et al., Soft Matter, 2020, 16, 1572-1581]. This suggests that fiber-shaped nanomaterials are more effective than spherical nanomaterials in enhancing the mechanical properties of ion gels. These results show that TOCNF can be used to toughen PIL-based ion gels and hence broaden their applications. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 77 2 2023 Urinary Retention Suggesting Aseptic Meningitis: Meningitis-Retention Syndrome Without Physical Signs of Meningeal Irritation 199 201 EN Tomohiro Nagano Department of Hematology, Japanese Red Cross Okayama Hospital Shinobu Hosokawa Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Hideaki Miyahara Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Kotaro Yamada Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Takayuki Umeno Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Hirohisa Kano Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Hiroe Kayatani Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Makoto Sakugawa Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Yasushi Takehisa Department of Neurology, Japanese Red Cross Okayama Hospital Tadasu Takenaka Department of Urology, Japanese Red Cross Okayama Hospital Makoto Takeuchi Department of Hematology, Japanese Red Cross Okayama Hospital Akihiro Bessho Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Case Report 10.18926/AMO/65150 Meningitis-retention syndrome (MRS) is the combination of aseptic meningitis and acute urinary retention that occurs in the absence of other neurological diseases. The cause(s) of MRS remain unclear. A 57-year-old Japanese woman was referred to our hospital for the evaluation of persistent fever and headache. The fever’s cause was initially unclear, but the presence of urinary retention raised concern about possible aseptic meningitis despite no physical indications of meningeal irritation. Only typical cases of MRS have been reported thus far to our knowledge, and it is important that clinicians are aware of MRS when it presents in this atypical form. 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.

Wiley Periodicals, INC Acta Medica Okayama 2055-5822 2023 Prevalence of transthyretin amyloidosis among heart failure patients with preserved ejection fraction in Japan EN Takanori Naito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukio Abe Department of Cardiology, Osaka City General Hospital Hiroyuki Watanabe Department of Cardiovascular Medicine, Tokyo Bay Urayasu Ichikawa Medical Center Satoru Sakuragi Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center Yusuke Katayama Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center Hajime Kihara Department of Internal Medicine, Kihara Cardiovascular Clinic Atsutaka Okizaki Department of Radiology, Asahikawa Medical University Yusuke Kawai Department of Cardiovascular Medicine, Okayama City Hospital Masaki Yoshikawa Department of Cardiovascular Medicine, Fukuyama City Hospital Atsushi Takaishi Department of Cardiology, Mitoyo General Hospital Hideki Fujio Department of Cardiovascular Medicine, Japanese Red Cross Society Himeji Hospital Hiroaki Otsuka Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center Soichiro Ogura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ATTR HFpEF Registry Investigators Aims Heart failure with preserved ejection fraction (HFpEF), which is caused by wide various conditions, has become a major public health problem. Transthyretin amyloid cardiomyopathy (ATTR-CM), which is thought to be an underdiagnosed disease, can cause HFpEF. Non-invasive diagnosis using 99mTechnetium (Tc)-pyrophosphate (PYP) scintigraphy enables accurate diagnosis of ATTR-CM. The aim of this study was to clarify the prevalence and characteristics of ATTR-CM among Japanese patients with HFpEF.<br> Methods and results This study was a multicentre, prospective, observational study conducted in Japan. We enrolled 373 patients with HFpEF [left ventricular (LV) ejection fraction ≥50%] aged ≥65 years who were admitted to the department of cardiology from September 2018 to January 2022. A 99mTc-PYP scintigraphy scan was performed during admission in all eligible patients. Cardiac 99mTc-PYP retention was graded according to a previously reported visual scale ranging from 0 to 3 points. The scan was considered positive when it revealed moderate-to-severe 99mTc-PYP uptake (Grade 2–3) in both ventricles. Patients were divided into ATTR-CM and non-ATTR-CM patients according to positive (Grade 2–3) or negative (Grade 0–1) 99mTc-PYP scintigraphy, respectively. Medical history, blood tests, electrocardiogram, echocardiography, and magnetic resonance imaging in the two groups of patients were compared. Among the 373 patients with HFpEF, 53 patients (14.2%; 95% confidence interval: 10.7–17.7) showed positive uptake on 99mTc-PYP scintigraphy. An endomyocardial biopsy was performed in 32 patients and confirmed amyloidosis in all cases. There were no significant differences between the two groups in age, severity of heart failure as assessed by the New York Heart Association (NYHA) functional classification, renal function values, left ventricular ejection fraction, and tricuspid regurgitant pressure gradient (ATTR-CM, n = 53 vs. non-ATTR-CM, n = 320). Patients in the ATTR-CM group had a higher N-terminal pro-brain natriuretic peptide level [2314 (1081–3398) vs. 900 (415–1828), P < 0.001], higher sensitive troponin T level (0.074 ± 0.049 vs. 0.035 ± 0.038, P < 0.001), and higher mean LV maximal wall thickness [12.5 (11–14) vs. 10.5 (9.5–11.5), P < 0.001].<br> Conclusions ATTR-CM is an underdiagnosed disease with a significant prevalence in Japanese patients with HFpEF. This study showed that results of examinations for ATTR-CM patients appear to be worse than those for non-ATTR-CM patients, but clinical severities of heart failure as assessed by the NYHA functional classification are similar in ATTR-CM and non-ATTR-CM patients, and the clinical overlap between ATTR-CM and non-ATTR-CM is high. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2023 Activated CTLA-4-independent immunosuppression of Treg cells disturbs CTLA-4 blockade-mediated antitumor immunity EN Tomofumi Watanabe Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takamasa Ishino Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Youki Ueda Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Joji Nagasaki Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuya Sadahira Department of Urology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiromichi Dansako Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoo Araki Department of Urology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yosuke Togashi Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Combination therapy with anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) monoclonal antibodies (mAbs) has dramatically improved the prognosis of patients with multiple types of cancer, including renal cell carcinoma (RCC). However, more than half of RCC patients fail to respond to this therapy. Regulatory T cells (Treg cells) are a subset of highly immunosuppressive CD4(+) T cells that promote the immune escape of tumors by suppressing effector T cells in the tumor microenvironment (TME) through various mechanisms. CTLA-4 is constitutively expressed in Treg cells and is regarded as a key molecule for Treg-cell-mediated immunosuppressive functions, suppressing antigen-presenting cells by binding to CD80/CD86. Reducing Treg cells in the TME with an anti-CTLA-4 mAb with antibody-dependent cellular cytotoxicity (ADCC) activity is considered an essential mechanism to achieve tumor regression. In contrast, we demonstrated that CTLA-4 blockade without ADCC activity enhanced CD28 costimulatory signaling pathways in Treg cells and promoted Treg-cell proliferation in mouse models. CTLA-4 blockade also augmented CTLA-4-independent immunosuppressive functions, including cytokine production, leading to insufficient antitumor effects. Similar results were also observed in human peripheral blood lymphocytes and tumor-infiltrating lymphocytes from patients with RCC. Our findings highlight the importance of Treg-cell depletion to achieve tumor regression in response to CTLA-4 blockade therapies. No potential conflict of interest relevant to this article was reported.

Elsevier B.V. Acta Medica Okayama 23523204 21 2022 Development of hydroxyapatite-coated nonwovens for efficient isolation of somatic stem cells from adipose tissues 52 61 EN Ryota Chijimatsu Okayama University Hospital, Center for Comprehensive Genomic Medicine Taiga Takeda The University of Tokyo, Bone and Cartilage Regenerative Medicine, Graduate School of Medicine Shinsaku Tsuji CPC Corporation Kohei Sasaki Japan Vilene Company, Ltd., Central Research Laboratory Koichi Kato Japan Vilene Company, Ltd., Central Research Laboratory Rie Kojima Japan Vilene Company, Ltd., Central Research Laboratory Noriko Michihata Japan Vilene Company, Ltd., Central Research Laboratory Toshiya Tsubaki The University of Tokyo, Sensory and Motor System Medicine, Graduate School of Medicine Aya Matui CPC Corporation Miharu Watanabe CPC Corporation Sakae Tanaka The University of Tokyo, Sensory and Motor System Medicine, Graduate School of Medicine Taku Saito The University of Tokyo, Sensory and Motor System Medicine, Graduate School of Medicine Adipose-derived stem cells (ASCs) are an attractive cell source for cell therapy. Despite the increasing number of clinical applications, the methodology for ASC isolation is not optimized for every individual. In this study, we developed an effective material to stabilize explant cultures from small-fragment adipose tissues.<br> Methods: Polypropylene/polyethylene nonwoven sheets were coated with hydroxyapatite (HA) particles. Adipose fragments were then placed on these sheets, and their ability to trap tissue was monitored during explant culture. The yield and properties of the cells were compared to those of cells isolated by conventional collagenase digestion.<br> Results: Hydroxyapatite-coated nonwovens immediately trapped adipose fragments when placed on the sheets. The adhesion was stable even in culture media, leading to cell migration and proliferation from the tissue along with the nonwoven fibers. A higher fiber density further enhanced cell growth. Although cells on nonwoven explants could not be fully collected with cell dissociation enzymes, the cell yield was significantly higher than that of conventional monolayer culture without impacting stem cell properties.<br> Conclusions: Hydroxyapatite-coated nonwovens are useful for the effective primary explant culture of connective tissues without enzymatic cell dissociation. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 00904295 170 2022 Simplified PADUA REnal (SPARE) Nephrometry System can Describe the Surgical Difficulty of Renal Masses With High Accuracy Even Without 3D Renal Models 132 138 EN Tomofumi Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takanori Sekito Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Maruyama 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 Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objective: To evaluate whether a 2-dimensional(2D) model describes the surgical difficulty of a renal mass accurately comparable to that obtained using a 3D model with the Simplified PADUA REnal nephrometry system (SPARE).<br> Methods: A total of 100 patients underwent RAPN in our hospital between October 2018 and May 2021. We excluded patients with CT images inappropriate for evaluation or for construction of 3D models, patients with multiple tumors, and those who underwent preoperative transcatheter arterial embolization. We conducted a retrospective analysis of the remaining patients using SPARE predictions from CT images (2D-SPARE) and SPARE predictions from 3D models (3D-SPARE). We evaluated the difference between the 2 nephrometry scores and compared them by their ability to predict the achievement of the desired surgical outcome: absence of positive margins, absence of ischemia, and absence of significant complications.<br> Results: A total of 87 patients were included in this study. Total score, and risk categorization using 3D-SPARE was significantly different from those using 2D-SPARE (P <.05), but in their areas under the curve (AUC), the scores and categorizations were not significantly different (score, 0.763 vs 0.742; P = .501; categorization, 0.711 vs 0.701; P = .755).<br> Conclusion: The SPARE system can describe the surgical difficulty of renal masses with high accuracy even without the use of 3D renal models. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 134 1 2022 令和２年度岡山医学会賞　総合研究奨励賞（結城賞） 1 3 EN Sumie Asano Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

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<br> 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.<br><br> Methods<br>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.<br><br> Results<br>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.<br><br> Conclusions<br> 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 Osteonecrosis of the Jaw in Two Rheumatoid Arthritis Patients Not Treated with a Bisphosphonate 111 116 EN Katsuhiko Amano Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akinari Sugauchi The first department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry Chiaki Yamada Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikihiko Kogo The first department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry Seiji Iida Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/64371 Medication-related osteonecrosis of the jaw (MRONJ) is a side effect in patients taking bone-modifying agents (BMAs), which are highly beneficial for treating osteoporosis and cancer. Bisphosphonates are prescribed to treat secondary osteoporosis in patients with rheumatoid arthritis (RA). We recently encountered two unusual cases of intraoral ONJ in RA patients who had not been treated with a BMA and did not have features of methotrexate- associated lymphoproliferative disorder. Their ONJ stage II bone exposures were treated by conservative therapy, providing good prognoses. These cases indicate that ONJ can occur in RA patients not treated with bisphosphonates. Several risk factors are discussed. No potential conflict of interest relevant to this article was reported.