International Institute of Anticancer Research Acta Medica Okayama 0250-7005 46 4 2026 P53-armed Oncolytic Adenovirus Enhances the Efficacy of PD-1 Blockade in Neuroblastoma by Inducing Immunogenic Cell Death 1769 1784 EN MORIMICHI TANI 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 HIROSHI NOUSO 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 YASUO URATA Oncolys BioPharma, Inc. SHUNSUKE KAGAWA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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. Although immunotherapy with immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) has emerged as novel antitumor therapy, high-risk NB tumors are refractory to ICI therapy. Oncolytic virotherapy is expected to potentiate the antitumor immune response by inducing immunogenic cell death (ICD). In the present study, we assessed the therapeutic potential of OBP-301 and OBP-702, telomerase-specific oncolytic adenoviruses, for the induction of ICD and combined effect with PD-1 blockade against NB cells. Materials and Methods: The cytopathic activity of OBP-301 and OBP-702 was assessed using three human MYCN-amplified NB cell lines (IMR-32, LA-N-5, and NB-1) and a murine non-MYCN-amplified NB cell line (Neuro-2a). Virus-mediated antitumor effect was assessed by analyzing cell viability, secretion of extracellular adenosine triphosphate (ATP) and high-mobility group box protein B1 (HMGB1), apoptosis, autophagy, and PD-L1 levels. A subcutaneous Neuro-2a tumor model was used to evaluate the in vivo antitumor effect of combination therapy with OBP-702 and anti-PD-1 antibody. Results: OBP-702 exhibited stronger cytopathic activity, inducing ICD with secretion of ATP and HMGB1, compared to OBP-301 in human and murine NB cells. OBP-301 and OBP-702 increased apoptosis, autophagy, and PD-L1 expression in murine NB cells. Moreover, OBP-702 significantly prolonged the survival of tumor-bearing mice compared to monotherapy with PD-1 blockade. Conclusion: OBP-702 is a promising antitumor strategy to promote the antitumor effect of ICIs by inducing ICD against NB tumors. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 0309-0167 2026 Clinicopathological and transcriptomic profiles of 101 patients with diffuse large B-cell lymphoma/high-grade B-cell lymphoma with double-hit MYC and BCL2 or BCL6 and triple hit EN Masashi Miyaoka Department of Pathology, School of Medicine, Tokai University Joaquim Carreras Department of Pathology, School of Medicine, Tokai University Yara Yukie Kikuti Department of Pathology, School of Medicine, Tokai University Haruka Ikoma Department of Pathology, School of Medicine, Tokai University Shunsuke Nagase Department of Pathology, School of Medicine, Tokai University Atsushi Ito Department of Pathology, School of Medicine Tokai University Isehara Japan Makoto Orita Department of Pathology, School of Medicine, Tokai University Hiroshi Kawada Department of Hematology, School of Medicine, Tokai University Rika Sakai Department of Medical Oncology, Kanagawa Cancer Center Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Kunihiro Tsukasaki Department of Hematology, International Medical Center, Saitama Medical University Shuji Momose Department of Pathology, Saitama Medical Center, Saitama Medical University Yoshihiro Kameoka Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine Masahiro Yoshida Department of Hematology, Osaka City General Hospital Akira Satou Department of Surgical Pathology, Aichi Medical University Hospital Seiichi Kato Center for Clinical Pathology, Fujita Health University Hospital Naoki Oishi Department of Pathology, University of Yamanashi Akio Saito Department of Hematology, NHO Shibukawa Medical Center Ken Sadahira Division of Hematology, Kawasaki Municipal Kawasaki Hospital Yohei Masugi Department of Pathology, School of Medicine, Tokai University Naoya Nakamura Department of Pathology, School of Medicine, Tokai University Aims: Diffuse large B-cell lymphoma/high-grade B-cell lymphoma (DLBCL/HGBCL) with MYC and BCL2 rearrangements (double-hit lymphoma with BCL2, DHL-BCL2) is a mature aggressive B-cell lymphoma that also includes concurrent triple hit with BCL6 translocation (TH). DHL with MYC and BCL6 (DH-BCL6) can also occur. The differences among these three DLBCL/HGBCL subtypes have not yet been definitively determined. Methods and Results: This study characterized the clinicopathological features and transcriptomic profiles of a series of 101 cases of DLBCL/HGBCL that were subclassified according to MYC, BCL2 and BCL6 FISH data, including cell-of-origin (COO)-like, molecular high-grade (MHG)-like and double-hit/dark-zone (DHIT/DZsig)-like signatures. DLBCL/HGBCL-DH-BCL2 was characterized by higher HGBCL morphology, CD10 positivity, GCB Hans's, GCB COO and MHG molecular subtype. DLBCL/HGBCL-TH had higher LDH levels and worse overall survival. DLBCL/HGBCL-DH-BCL6 had higher MUM1 expression, non-GCB Hans', ABC/Unclassified COO, non-MHG and low DHIT/DZ signatures. Transcriptomic analysis showed that DLBCL/HGBCL-DH-BCL2 and DLBCL/HGBCL-TH were close but separated from DLBCL/HGBCL-DH-BCL6. Gene set enrichment analysis (GSEA) revealed different levels of enrichment between the subtypes. Conclusions: DLBCL/HGBCL-DH-BCL6 differs from the DLBCL/HGBCL-DH-BCL2, and the DLBCL/HGBCL-TH is associated with the worst survival. Analysis of all three genes of MYC, BCL2 and BCL6 is recommended in the context of DLBCL/HGBCL diagnosis. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2688-4046 6 3 2026 PPy‐Coated Wire Actuators for the Micromechanostimulation of Cells: Fabrication and Characterization e202500639 EN Amaia B. Ortega‐Santos Sensor and Actuator Systems, Department of Physics Chemistry and Biology (IFM), Linköping University Satoru Hayano Department of Orthodontics, Okayama University Hospital Emilio Satoshi Hara Advanced Research Center for Oral and Craniofacial Sciences Dental School, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jose G. Martínez Sensor and Actuator Systems, Department of Physics Chemistry and Biology (IFM), Linköping University Hiroshi Kamioka Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Edwin W. H. Jager Sensor and Actuator Systems, Department of Physics Chemistry and Biology (IFM), Linköping University Cellular mechanotransduction signals play a crucial role in physiological and pathological conditions, including skeletal disorders. Although various systems exist to mechanically stimulate cultured cells, most are constrained by incubator incompatibility, limited physiological relevance, nonuniform stimulation, or complexity. The objective of this article is to develop and validate a compact, incubator-compatible tool capable of delivering localized and physiologically relevant mechanical stimulation to small cell populations. Here, we introduce a polypyrrole-based wire-shaped microactuator designed to induce localized mechanical stress to adjacent cells. These wire-shaped microactuators are biocompatible, easy-to-use, and compact for use within standard in vitro cell culture systems. Using a noncontact optical method, we characterize the actuation of polypyrrole-coated wires in an aqueous NaDBS electrolyte, showing radial expansion of 1.5–8 µm depending on the deposited polypyrrole film thickness, comparable to cellular dimensions. Next, the actuation is confirmed to be robust and stable to use in cell culture media at physiological temperature. To evaluate biological relevance, osteoblastic KUSA-A1 cells are mechanically stimulated inside the incubator and transcriptomic changes are assessed. Mechanical stimulation resulted in upregulation of genes previously associated with mechanotransduction, including Fos and Fosb. Additionally, several uncharacterized long noncoding RNAs are differentially expressed, suggesting potential novel players in the mechanotransduction pathway. No potential conflict of interest relevant to this article was reported.

岡山大学理学部地球科学科 Acta Medica Okayama 1340-7414 32 1 2026 岡山平野児島湾岸部での微動アレイ探査 1 7 EN Nobuyuki YAMADA Faculty of Science and Technology, Kochi University Hiroshi TAKENAKA Department of Earth Sciences, Okayama University 10.18926/ESR/70294 　This report describes microtremor array observations conducted at two sites for deep exploration and three sites for shallow exploration around Kojima Bay area in the southern Okayama Plain. Based on these records, the ground velocity structures were estimated. The results yielded solutions indicating the depth of the top of the seismic base layer (equivalent to 3 km/s layer) ranges from 140 to 300 m, while the depth of the top of the engineering basement layer (equivalent to 0.6 km/s layer) is approximately about 13–14 m. The shallow exploration results also suggested the possible presence of an inversion layer. These estimated velocity structure models provided a reasonable explanation for the observed phase velocities. No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 61 2026 「国郡志御編集ニ付下調べ書出し帳」にみる広島藩の歌謡田植 ― 大田植の分布と種類に対する一つのアプローチ ― 65 84 EN Hiroshi TAKANO 10.18926/70278 No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1547-5271 22 9 2025 Aging of the tricuspid valve annulus detected by photon-counting detector computed tomography: Importance of aortic root compression on occurrence of arrhythmias e772 e780 EN Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Koji Nakagawa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Satoshi Nagase Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center Yoshihisa Morimoto Department of Cardiovascular Medicine, Fukuyama City Hospital Takuro Masuda Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Akira Ueoka Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Saori Asada Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Masakazu Miyamoto Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Norihisa Toh Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Toru Miyoshi Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Nobuhiro Nishii Department of Cardiovascular Therapeutics, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Background The aortic root compresses the heart in elderly patients, potentially influencing the conduction system and causing atrial tachyarrhythmias. However, actual anatomic alterations in the right side of the heart because of aortic root compression have not yet been fully evaluated. Objective This study aimed to elucidate the alterations in the tricuspid valve annulus (TVA) caused by aortic root compression using a 3-dimensional endoscopic view of the heart constructed by photon-counting detector computed tomography, an emerging medical technology. Methods We analyzed 147 consecutive patients who underwent photon-counting detector computed tomography at our institute after excluding those with diseases that directly influenced the right side of the heart. Results Aortic root compression caused significant TVA deformation. We defined severe TVA compression as the length of the TVA compressed by the aortic root ≥80% of the major axis of the TVA. Severe compression was more prevalent in elderly patients (age ≥75 years [44%]; P < .01). The distance between the membranous septum and ostium of the coronary sinus was shortened, whereas the cavotricuspid isthmus was elongated in older patients. The regression analysis identified aging as a significant contributor to TVA compression. The short minor and long major axes of the TVA, incidence of atrial tachyarrhythmias (74% vs 45%; P < .01), and atrioventricular conduction disturbances (35% vs 15%; P < .01) were more frequently observed in patients with severe compression. Conclusion Aortic root compression deforms the TVA and alters the anatomic relationship between the atrioventricular conduction system and the cavotricuspid isthmus. Therefore, aortic root compression may contribute to the occurrence of atrial tachyarrhythmias and conduction disturbances in older patients. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0732-8893 115 3 2026 Investigation of the cefazolin inoculum effect in blood culture-isolated methicillin-susceptible Staphylococcus aureus strains: A Japanese multicenter study 117345 EN Shinnosuke Fukushima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuma Tsuji Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Sakura Ogawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihito Koyanagi Department of Clinical Laboratory, Chutoen General Medical Center Yuji Ito Department of General Internal Medicine, Chutoen General Medical Center Hiroshi Koganemaru Department of Infectious Diseases, Tokyo Metropolitan Institute for Geriatrics and Gerontology Atsushi Yoshida Department of Infectious Diseases, Tokyo Metropolitan Institute for Geriatrics and Gerontology Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background: Cefazolin inoculum effect (CInE) is a microbiological phenomenon where the MIC of cefazolin against methicillin-susceptible Staphylococcus aureus (MSSA) strains increases with higher bacterial volumes. Method: We retrospectively investigated the prevalence and characteristics of the CInE among MSSA strains isolated from blood cultures at three Japanese hospitals. The collected isolates were screened for blaZ using PCR, and the cefazolin minimum inhibitory concentration (MIC) for the blaZ-positive MSSA isolates was measured at standard and high inoculum volumes. CInE-positive MSSA strains were defined as those with a cefazolin MIC ≥16 μg/mL at 107 CFU/mL and ≤8 μg/mL at 105 CFU/mL. In these blaZ-positive strains, we performed blaZ typing and tested a modified nitrocefin-based rapid examination to detect the CInE. Results: We collected 329 MSSA strains isolated from blood cultures. Of these, 96 (29.2%) were positive for the blaZ gene, with the following genotypes: type A (15, 15.6%), type B (3, 3.1%), type C (77, 80.2%), type D (0, 0.0%), and non-type (1, 1.0%). Among 96 blaZ-positive MSSA isolates, 11 exhibited the CInE, all of which harbored blaZ type A. The rapid nitrocefin test detected CInE positivity with high sensitivity (100%), specificity (94.1%), and diagnostic accuracy (94.8%). Conclusion: This study highlighted the low prevalence of CInE-presenting MSSA isolates in Japan. When the cefazolin MIC is ≥1 μg/mL or the penicillin G MIC is ≥0.25 μg/mL, the rapid nitrocefin test may be useful for considering the CInE in patients with high bacterial volume MSSA infections. No potential conflict of interest relevant to this article was reported.

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

大阪府保険医協会 Acta Medica Okayama 54 713 2026 『光が見える』人工網膜の可能性 ― 有機色素分子を部材とする世界初の医療機器「光電変換色素薄膜型人工網膜OUReP」 13 21 EN Toshihiko Matsuo Tetsuya Uchida Hiroshi Ishikane 　網膜色素変性や加齢黄斑変性では、光を細胞膜電位に変換する網膜視細胞が死んでいるが、視神経として脳に連絡する神経節細胞は生き残っている。人工網膜は視細胞を代替する人工物で、光を受け電流を出力する電極アレイ型が主流であるが、電流は拡散するため解像度向上が難しい。そこで人工網膜の解像度向上を目指して、光を電位差に変換する光電変換色素分子を絶縁体のポリエチレン薄膜表面に共有結合した光電変換色素薄膜型の人工網膜OURePを開発してきた。この人工網膜OURePは光受容と電位出力の一体型で外部起電力は不要、手術では薄膜を鋏で切って眼内に植込む大きさを自由に選べる。使い捨てインジェクタを使って薄膜を丸め眼球の網膜下に硝子体手術で植込み、網膜下に植込んだ人工網膜OURePは光を受けて電位差を出力し隣接する網膜組織の神経細胞の活動電位を誘発する。クリーンルームで製造品質管理を行い、安全性と有効性を証明して、医師主導治験を準備している。今後、日本の国民皆保険が維持できるよう比較安価な適正価格の人工網膜治療を提供したい。 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. 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. 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. 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.

岡山大学教育推進機構 Acta Medica Okayama 1881-5952 3 2026 Developing a Short-form Scale to Assess Learner Beliefs Regarding English Learning Strategies 100 119 EN Hiroshi MORITANI Institute for Promotion of Education and Campus Life, Okayama University Alexis PUSINA Institute for Promotion of Education and Campus Life, Okayama University 10.18926/70115 Questionnaire surveys are a prevalent method in applied linguistics for investigating complex constructs, such as learner beliefs. However, their complex nature often creates overly lengthy instruments, making them impractical for classroom use or for obtaining timely educational insights. This study aimed to develop a simplified, yet robust version of an existing learner belief scale to address these challenges. The authors carefully selected 24 belief-specific items from an initial pool of 78 items from a previous study for use in an online survey, which was completed by 246 participants. The data were subject to exploratory factor analysis. This process resulted in a concise 12-item scale, could offer a more practical tool for language educators. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 2169-7574 14 2 2026 A Technique for Repositioning the Posteriorly Displaced Premaxilla Following Prior Repair of Complete Bilateral Cleft Lip e7467 EN Yuki Arimura Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Iida Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aiko Hyodo Advanced Cleft Lip and Cleft Palate Center, Okayama University Hospital Ayaka Mikami Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Hayano Advanced Cleft Lip and Cleft Palate Center, Okayama University Hospital Fumiko Takemoto Advanced Cleft Lip and Cleft Palate Center, Okayama University Hospital Hiroshi Kamioka Advanced Cleft Lip and Cleft Palate Center, Okayama University Hospital It is well known that osteotomy of the premaxilla is an effective surgical procedure for the correction of a displaced premaxilla in patients with bilateral cleft lip and palate. In cases with a posteriorly displaced premaxilla, it is not easy to move the premaxilla forward because of scarring of the palatal mucosal attachment, narrowing of the adjacent maxillary segments, and the stable fixation of this bone segment after its movement. This fixation is also important in cases without secondary bone grafting. We propose a new method that combines osteotomy and a method such as bone distraction for cases with significant premaxilla displacement that are difficult to repair by osteotomy alone. A conventional orthodontic palatal expander was used as the distractor. The anterior arms were bent at the posterior part of the lingual side of the anterior teeth, and a resin base was attached to the arm parts. The posterior arms were bent and waxed onto the bands of both first molars. Supportive stainless steel wire arms, which are attached to the rest of the deciduous molars, stabilize the distractor. After the osteotomy of the premaxilla, distraction was performed at a rate of 1.0 mm per day, starting the day after surgery. Because the premaxilla of patients with bilateral cleft lip and palate has undergone multiple surgical interventions, the soft tissue is not mobile, making it impossible to guide the premaxilla to an ideal position in a single stage. However, this procedure, using this semirigid distractor, makes it possible to move the osteotomized premaxilla to the planned position with firm stability. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 2026 Turning pancreatic cancer from cold to hot: the promise of a p53-expressing oncolytic adenovirus (OBP-702) EN Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Center for Innovative Clinical Medicine, Okayama University Hospital Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma Inc Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pancreatic cancer remains one of the most lethal malignancies, with limited therapeutic options and poor responsiveness to immune checkpoint inhibitors (ICIs). This resistance is largely attributed to its profoundly immunosuppressive and desmoplastic tumor microenvironment (TME), characterized by low tumor mutational burden, dense stroma, and abundant immunosuppressive cell populations. Therefore, strategies capable of enhancing tumor immunogenicity and overcoming immune evasion are urgently needed. Oncolytic virotherapy is a promising approach, offering not only tumor-selective cytotoxicity, but also potent immunomodulatory effects. Of these agents, Telomelysin (OBP-301, Suratadenoturev), a telomerase-specific oncolytic adenovirus, demonstrated clinical safety but limited efficacy in refractory tumors. To address this challenge, we developed OBP-702, a next-generation, p53-armed, oncolytic adenovirus designed to augment antitumor activity. Preclinical studies have shown that OBP-702 exerts robust cytotoxicity through multiple mechanisms, including p53-mediated apoptosis and autophagy, E1A–E2F1-mediated p21 suppression, and inhibition of oncogenic KRAS pathways. Importantly, OBP-702 induces strong immunogenic cell death, activates dendritic cells, and promotes tumor-specific T-cell responses, effectively converting immunologically “cold” pancreatic tumors into “hot” tumors. OBP-702 also remodels the immunosuppressive TME by reducing granulocyte–macrophage colony-stimulating factor (GM-CSF) secretion, suppressing myeloid-derived suppressor cells (MDSCs), and targeting stromal components, such as cancer-associated fibroblasts (CAFs). These effects contribute to enhanced responses to ICIs and standard chemotherapies. Given its multifaceted antitumor functions and ability to overcome key barriers in pancreatic cancer, OBP-702 represents a highly promising therapeutic candidate. A first-in-human clinical trial evaluating endoscopic ultrasonography-guided intratumoral injection of OBP-702 is currently in preparation, expected to advance clinical translation of this novel virotherapeutic strategy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Usefulness of D-dimer Assay to Confirm the Course of Overt Venous Thromboembolism (VTE) in Cancer Patients 1 7 EN Hidenaru Yamaoka Department of Cardiovascular Medicine, IMS Tokyo Katsushika General Hospital Masashi Yoshida Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshihiro Sarashina Seisukai Kuroda Clinic Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuru Munemasa Department of Cardiovascular Medicine, Okayama Rosai Hospital Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ito Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/70067 Venous thromboembolism (VTE) is a serious complication in patients with cancer. In this population, the presence of thrombi is often assessed at cancer diagnosis by measuring D-dimer levels, which have high sensitivity but low specificity for identifying VTE at this clinical time point. However, the usefulness of D-dimer measurement during anticoagulation therapy has not been fully established, despite its widespread use. In this retrospective observational study, we investigated whether D-dimer measurement during anticoagulation therapy in cancer patients could predict overt VTE at follow-up. The study included patients who underwent D-dimer testing and contrast-enhanced computed tomography between 30 and 100 days after initiation of anticoagulation therapy. Eighty-two patients were included: 60 with cancer and 22 without. The diagnostic performance of D-dimer for overt VTE was as follows: sensitivity, 85.7%; specificity, 87.2%; positive predictive value, 78.3%; and negative predictive value, 89.2%. These findings suggest that D-dimer measurement at follow-up has high sensitivity and specificity for overt VTE in cancer patients and may aid in assessing thrombotic status. Clinically, if anticoagulation therapy is continued until D-dimer levels become negative, the absence of overt VTE could be inferred without additional invasive testing. No potential conflict of interest relevant to this article was reported.

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

MDPI AG Acta Medica Okayama 2221-3759 14 1 2026 The Influence of Fluidic Flow Stress on the Development of the Secondary Palate 9 EN Masayo Nagata Department of Orthodontics, Okayama University Hospital Satoru Hayano Department of Orthodontics, Okayama University Hospital Ziyi Wang Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takahiro Kosami Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Kamioka Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Craniofacial development is orchestrated by a finely regulated interplay of numerous genes and signaling pathways. Palatogenesis proceeds through a complex, stepwise process, in which endogenous mechanical stresses within tissues have been implicated. However, the impact of exogenous fluidic flow mechanical stress derived from maternal movement on palatal development remains unclear. In this study, we investigated the effect of exogenous fluidic flow mechanical stress on palatal morphogenesis, focusing on the horizontal outgrowth of palatal shelves after elevation. Palatal tissues dissected from mouse embryos were subjected to organ culture with or without mechanical loading (loaded and unloaded groups, respectively). Stress magnitude was quantified by calculating wave energy, and morphometric and molecular analyses were performed. Compared with the unloaded group, palatal shelves in the loaded group showed significant increases in thickness and volume, accompanied by enhanced cell proliferation, nuclear translocation of YAP and β-catenin, and upregulation of the osteogenic markers Osterix and Osteocalcin. No significant difference in apoptosis was observed. These findings indicate that exogenous mechanical stress promotes cell proliferation and osteogenic differentiation through the Hippo and WNT/β-catenin pathways in palate explants. Our results suggest that moderate maternal movement-induced mechanical stress contributes to normal palatogenesis, providing new insights into the mechanisms underlying cleft palate. No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 大田植の分布と種類に関する検討（3）―岡山県・広島県の自治体史等における記述・資料― 1 18 EN Hiroshi TAKANO 10.18926/70017 No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1521-6543 65 4 2013 Synthesis of biopterin and related pterin glycosides 300 309 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Hiroshi Yamamoto School of Pharmacy, Shujitsu University Certain pterins having a hydroxyalkyl side chain at C-6 have been found as glycosidic forms in certain prokaryotes, such as 2′-O-(α-D-glucopyranosyl)biopterin from various kinds of cyanobacteria, and limipterin from a green sulfur photosynthetic bacterium. Synthetic studies on glycosides of biopterin and related pterins have been made in view of the structural proof as well as for closer examination of their biological activities and functions. The syntheses of these natural pterin glycosides have effectively been achieved, mostly through appropriately protected N2-(N,N-dimethylaminomethylene)-3-[2-(4-nitrophenyl)ethyl]pterin derivatives as glycosyl acceptors, and are reviewed here. © 2013 IUBMB Life 65(4):300–309, 2013. No potential conflict of interest relevant to this article was reported.

The Japan Institute of Heterocyclic Chemistry Acta Medica Okayama 0385-5414 70 1 2006 Synthesis of 6- and 7-(1,2,3-Trihydroxy-1,2-O-isopropylidenepropyl)pteridines and Deoxygenation of Their 3’-Hydroxy Groups 355 365 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Daisuke Takayama Department of Chemistry, Faculty of Science, Okayama University Hiroshi Yamamoto Department of Chemistry, Faculty of Science, Okayama University Treatment of 3,4-O-isopropylidene-L-threo-pentos-2-ulose (7) with 5,6-diamino-1,3-dimethyluracil (8) afforded 1,3-dimethyl-6-[(1R,2S)-1,2,3-trihydroxy-1,2-O-isopropylidenepropyl]lumazine (9a) and its 7-substituted isomer (9b). Deoxygenation of 3’-hydroxy groups of 9a,b was investigated in connection with a practical transformation of neopterin into biopterin. No potential conflict of interest relevant to this article was reported.

The Japan Institute of Heterocyclic Chemistry Acta Medica Okayama 0385-5414 85 10 2012 Synthetic Studies on Natural Pterin Glycosides 2375 2390 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Hiroshi Yamamoto School of Pharmacy, Shujitsu University Some pterins having various kind of sugars attached to the hydroxyalkyl side-chain at C-6 are known to occur in certain prokaryotes as exemplified by 2'-O-(α-D-glucopyranosyl)biopterin isolated from various kinds of cyanobacteria. A synthetic exploration of various types of glycosides of biopterin and related pterins has been undertaken owing to a marked interest in their physiological functions and biological activities as well as the structural proof of those natural products. This review summarizes our synthetic studies on natural pterin glycosides by employing the appropriately protected N2-(N,N-dimethylaminomethylene)-3-[2-(4-nitrophenyl)ethyl]pterin derivatives as glycosyl accepters. No potential conflict of interest relevant to this article was reported.

The Japan Institute of Heterocyclic Chemistry Acta Medica Okayama 0385-5414 69 1 2006 Synthesis of Functionalized Phospholane Oxides and Phosphorinane Oxides from 1,4- and 1,5-Di-O-Mesyloxy Compounds 283 294 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Karsten Schürrle Department of Chemistry, Faculty of Science, Okayama University Hiroshi Yamamoto Department of Chemistry, Faculty of Science, Okayama University Treatment of 1,4-di-O-mesyl-2,3-di-O-methyl-L-threitol (8b) with phenylphosphine in the presence of sodium hydride in DMSO, followed by the action of hydrogen peroxide, afforded 3,4-dimethoxy-1-phenylphospholane 1- oxide (7), while the same treatment of 1,5-di-O-mesyl-2,3,4-tri-O-methyl-meso- xylitol (11b) provided 2,3,4-trimethoxy-1-phenylphosphorinane 1-oxide (14). No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0040-8166 93 2025 Detection of the nuclear translocation of androgen receptor using quantitative and automatic cell imaging analysis 102631 EN Lanlan Bai Graduate School of Science and Engineering, Iwate University Tao Wu Graduate School of Science and Engineering, Iwate University Mizuki Fukasawa Neuro-AI Integration Science Laboratory, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Sayo Kashiwagi Rohto Pharmaceutical Co., Ltd., Basic Research Development Division Haruka Tate Graduate School of Science and Engineering, Iwate University Taku Ozaki Graduate School of Science and Engineering, Iwate University Eriko Sugano Graduate School of Science and Engineering, Iwate University Hiroshi Tomita Graduate School of Science and Engineering, Iwate University Tsuyoshi Ishii Rohto Pharmaceutical Co., Ltd., Basic Research Development Division Takuya Akashi Neuro-AI Integration Science Laboratory, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Tomokazu Fukuda Graduate School of Science and Engineering, Iwate University Testosterone signaling mediates diseases such as androgenetic alopecia and prostate cancer and is controlled by the activation of the androgen receptor (AR) and nuclear translocation of the ligand-receptor complex. This study established an immortalized dermal papilla cell line that stably expresses the AR labeled with a monomeric green fluorescence marker. The cells expressed the histone H2B protein as visualized using a red fluorescence marker, enabling the Detection of nuclear translocation under live cell conditions using image analysis. The AR was observed to be translocated from the cytoplasm to the nucleus of cells after stimulation with dihydrotestosterone (DHT). The signal intensity of the nuclear/cytoplasm ratio was analyzed using automatic image analysis and a newly developed algorithm. The quantitation method to detect nuclear translocation revealed that the AR nuclear signal plateaued approximately 20 min after DHT exposure. Our developed method has the potential to save human labor by the automatic process of the image. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-0851 75 1 2025 Gut microbial metabolite butyrate boosts p53-expressing telomerase-specific oncolytic adenovirus efficacy by enhancing infectivity and activating MHC-I/cGAS-STING 10 EN Masaki Sakamoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Katayama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yu Mikane Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunya Hanzawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Kadowaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Hamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoma Sugimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiaki Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The gut microbiota plays an essential role in regulating host immunity, and its metabolites such as butyrate exert immunomodulatory effects by acting as histone deacetylase inhibitors. Oncolytic virotherapy has emerged as a promising approach for cancer treatment, and we have developed OBP-702, a telomerase-specific oncolytic adenovirus that expresses p53 and elicits strong systemic antitumor responses. In this study, the potential synergy between butyrate and OBP-702 was investigated in colorectal cancer models. Using human and murine colorectal carcinoma cell lines, butyrate was found to directly enhance the infectivity of OBP-702 by upregulating CAR and integrins, thereby promoting apoptosis and autophagy in tumor cells. In addition, butyrate indirectly boosted systemic antitumor immunity by upregulating MHC-I expression through activation of the cGAS-STING pathway and enhancing CD8 + T cell recruitment via CXCL10 secretion. These findings were supported by in vivo experiments using CT26 subcutaneous, bilateral, and orthotopic tumor models, in which the combination of oral butyrate and intratumoral OBP-702 administration produced synergistic antitumor effects. These results highlight the therapeutic potential of integrating gut microbial metabolites with oncolytic virotherapy as a novel immunotherapeutic strategy for colorectal cancer. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0006-2960 64 20 2025 Characterization of Autonomous and Ca2+/Calmodulin-Dependent Activities of CaMKK Isoforms In Vitro and in Mouse Tissues 4309 4317 EN Satomi Ohtsuka Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yerun Chen Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masaki Magari Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Teruhiko Ishikawa Department of Science Education, Graduate School of Education, Okayama University Hiroyuki Sakagami Department of Anatomy, Kitasato University School of Medicine Futoshi Suizu Clinical Examination Department, Kagawa Prefectural University of Health Sciences Hiroshi Tokumitsu Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ca2+/CaM-dependent protein kinase kinase (CaMKK) phosphorylates and activates downstream kinases, including CaMKI, CaMKIV, PKB, and AMPK, regulating various cellular functions such as neuronal morphogenesis, metabolic control, and pathophysiological pathways, such as cancer progression. CaMKKα/1 is tightly regulated by an autoinhibitory mechanism. CaMKKβ/2 activity is highly Ca2+/CaM-independent (autonomous activity) in vitro and Ca2+/CaM-dependent in cultured cells. Whether these two activity states of CaMKKβ/2 exist in vivo and the detailed regulatory mechanisms for the transition of both activity states remain unclear due to the difficulty in distinguishing the two activity states. In this study, we detected Ca2+-dependent and autonomous CaMKK activity in HeLa cells and successfully separated both activity states of CaMKKβ/2 in mouse brain and testis extracts using a recently developed CaMKK inhibitor (TIM-063)-coupled sepharose, which binds to the catalytic domain in the active state but not in the autoinhibited state. Furthermore, lambda protein phosphatase treatment converted the Ca2+/CaM-dependent form to the autonomous form of CaMKKβ/2, which was not affected by Ala mutation of Ser128, Ser132, and Ser136. The two activity forms of CaMKKβ/2 had equivalent Ca2+/CaM-binding ability. The findings demonstrate the presence of autonomous and Ca2+/CaM-dependent forms of CaMKKβ/2 independently in mouse tissues and cultured cells. The transition of these states of CaMKKβ/2 may be dynamically regulated by the phosphorylation/dephosphorylation of serine residues in the N-terminal regulatory domain. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 0250-7005 46 1 2025 P53-Armed Oncolytic Virotherapy Promotes the Efficacy of PD1 Blockade in Murine Osteosarcoma Tumors 69 84 EN MIHO KURE 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 KOJI DEMIYA Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences HIROYA KONDO 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 TADASHI KOMATSUBARA 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 KOJI UOTANI Department of Orthopaedic 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 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 Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences SHUNSUKE KAGAWA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 Background/Aim: Osteosarcoma (OS) is refractory to immune checkpoint inhibitors targeting programmed cell death 1 (PD1)/PD ligand 1 (PD-L1) due to poor immune response. We previously developed telomerase-specific, replication-competent oncolytic adenoviruses non-armed OBP-301 and P53-armed OBP-702 that exert antitumor efficacy against human OS cells. Recently, we demonstrated that P53-armed OBP-702 induces more profound immunogenic cell death and antitumor immune response against human and murine OS cells than does non-armed OBP-301. In the present study, we assessed the combined efficacy of PD1 blockade and P53-armed OBP-702 against murine OS cells. Materials and Methods: Three murine OS cell lines (K7M2, NHOS, NHOS-LM4) were used to assess the cytopathic effect of non-armed OBP-301 and P53-armed OBP-702 by XTT assay. Virus-induced immunogenic cell death was assessed by analyzing the levels of extracellular adenosine triphosphate and high-mobility group box protein B1. The expression of PD-L1 and PD-L2 was analyzed by flow cytometry. The malignant potential of NHOS-LM4 cells was analyzed by a migration and invasion assay. An orthotopic NHOS-LM4 tumor model was used to evaluate the antitumor efficacy of combination therapy with P53-armed OBP-702 and anti-PD1. Results: P53-armed OBP-702 exhibited antitumor potential for the induction of immunogenic cell death, apoptosis, autophagy, and PD-L1/2 upregulation in K7M2 and NHOS cells. NHOS-LM4 cells showed increased migratory and invasive ability compared to NHOS cells. P53-armed OBP-702 significantly suppressed the malignant potential of NHOS-LM4 cells. Combination dosing showed that P53-armed OBP-702 significantly promoted the antitumor effect of PD1 blockade against NHOS-LM4 tumors. Conclusion: Our results suggest that P53-armed OBP-702 is a promising agent for improving the antitumor effect of PD1 blockade in treating invasive OS. 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. 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. 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. 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.

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

Elsevier BV Acta Medica Okayama 2666-0849 30 32 2025 Guide Tip Damage Due to Rotablation 105347 EN Satoshi Taya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Masatoki Yoshida Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hironobu Toda Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morita Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Background: The rotational atherectomy system can effectively debulk calcified coronary lesions. However, rare complications specific to that system have been reported. Case Summary: A 77-year-old man with a heavily calcified lesion in the right coronary artery (RCA) ostium underwent percutaneous coronary intervention in an 8-F system. During the procedure, rotablation with a 2.25-mm burr was required. After the percutaneous coronary intervention, partial loss of the tip of the guide was observed. He had no clinical sequelae despite the presumed retained catheter material in his body. Discussion: Although insufficient guide coaxiality has been suggested as the primary cause of guide tip fracture during RCA ostial ablation, other factors may have contributed: the application of force to the tip and a small difference in size between the guide and the burr. Take-Home Message: When ablating RCA ostial lesions, positioning the burr platform outside the guide may help prevent similar complications in future cases. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1547-5271 22 12 2025 Virtual endoscopic imaging of the heart using photon-counting detector computed tomography for electrophysiologists 3199 3207 EN Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Saori Asada Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Masakazu Miyamoto Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Koji Nakagawa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Satoshi Nagase Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center Yoshimasa Morimoto Department of Cardiovascular Medicine, Fukuyama City Hospital Satoshi Kawada Department of Cardiovascular Medicine, Kochi Health Science Center Tadashi Wada Department of Cardiology, National Hospital Organization Iwakuni Clinical Center Takuro Masuda Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Akira Ueoka Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Norihisa Toh Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Toru Miyoshi Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Nobuhiro Nishii Department of Cardiovascular Therapeutics, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 14 14 2025 Symptomatic Trends and Time to Recovery for Long COVID Patients Infected During the Omicron Phase 4918 EN Hiroshi Akiyama Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasue Sakurada Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Honda Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yui Matsuda Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Otsuka Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuki Tokumasu Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuhiro Nakano Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryosuke Takase Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Omura Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keigo Ueda Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumio Otsuka Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Since the pathophysiology of long COVID is not yet fully understood, there are no specific methods for its treatment; however, its individual symptoms can currently be treated. Long COVID is characterized by symptoms that persist at least 2 to 3 months after contracting COVID-19, although it is difficult to predict how long such symptoms may persist. Methods: In the present study, 774 patients who first visited our outpatient clinic during the Omicron period from February 2022 to October 2024 were divided into two groups: the early recovery (ER) group (370 cases; 47.8%), who recovered in less than 180 days (median 33 days), and the persistent-symptom (PS) group (404 cases; 52.2%), who had symptoms that persisted for more than 180 days (median 437 days). The differences in clinical characteristics between these two groups were evaluated. Results: Although the median age of the two groups did not significantly differ (40 and 42 in ER and PS groups, respectively), the ratio of female patients was significantly higher in the PS group than the ER group (59.4% vs. 47.3%). There were no significant differences between the two groups in terms of the period after infection, habits, BMI, severity of COVID-19, and vaccination history. Notably, at the first visit, female patients in the PS group had a significantly higher rate of complaints of fatigue, insomnia, memory disturbance, and paresthesia, while male patients in the PS group showed significantly higher rates of fatigue and headache complaints. Patients with more than three symptoms at the first visit were predominant in the PS groups in both genders. Notably, one to two symptoms were predominant in the male ER group, while two to three symptoms were mostly reported in the female PS group. Moreover, the patients in the PS group had significantly higher scores for physical and mental fatigue and for depressive symptoms. Conclusions: Collectively, these results suggest that long-lasting long COVID is related to the number of symptoms and presents gender-dependent differences. No potential conflict of interest relevant to this article was reported.

Biophysical Society of Japan Acta Medica Okayama 2189-4779 22 3 2025 Origin of the unique topology of the triangular water cluster in Rubrobacter xylanophilus rhodopsin e220018 EN Tomoyasu Noji Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo Masaki Tsujimura Department of Advanced Interdisciplinary Studies, The University of Tokyo Keisuke Saito Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo Keiichi Kojima Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Sudo Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Ishikita Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo The crystal structure of Rubrobacter xylanophilus rhodopsin (RxR) reveals a triangular cluster of three water molecules (W413, W415, and W419) at the extracellular proton-release site, near Glu187 and Glu197. Using a quantum mechanical/molecular mechanical approach, we identified the structural nature of this unique water cluster. The triangular shape is best reproduced when all three water molecules are neutral H2O with protonated Glu187 and deprotonated Glu197. Attempts to place H3O+ at any of these water molecules result in spontaneous proton transfer to one of the acidic residues and significant distortion from the crystal structure. The plane defined by the triangular water cluster extends into the guanidinium plane of Arg71, with both aligned along the W413...W419 axis. This extended plane lies nearly perpendicular to a five-membered, ring-like H-bond network involving two carboxyl oxygen atoms from Glu187 and one from Glu197. The resulting bipartite planar architecture, defined by the water triangle, Arg71, and the Glu187/Glu197 network may reflect the exceptional thermal stability in RxR. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1433-7851 64 13 2025 Conduction Band and Defect Engineering for the Prominent Visible‐Light Responsive Photocatalysts e202419624 EN Akira Yamakata Graduate School of Natural Science and Technology, Okayama University Kosaku Kato Graduate School of Natural Science and Technology, Okayama University Takafumi Ogawa Nanostructures Research Laboratory, Japan Fine Ceramics Center Kanta Ogawa Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Makoto Ogawa Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Daichi Kato Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Chengchao Zhong Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Akihide Kuwabara Nanostructures Research Laboratory, Japan Fine Ceramics Center Ryu Abe Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Hiroshi Kageyama Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering, Kyoto University Controlling trap depth is crucial to improve photocatalytic activity, but designing such crystal structures has been challenging. In this study, we discovered that in 2D materials like BiOCl and Bi4NbO8Cl, composed of interleaved [Bi2O2]2+ and Cl- slabs, the trap depth can be controlled by manipulating the slab stacking structure. In BiOCl, oxygen vacancies (VO) create deep electron traps, while chlorine vacancies (VCl) produce shallow traps. The depth is determined by the coordination around anion vacancies: VO forms strong σ bonds with Bi-6p dangling bonds below the conduction band minimum (CBM), while those around Cl are parallel, forming weak π-bonding. The strong re-hybridization makes the trap depth deeper. In Bi4NbO8Cl, VCl also creates shallow traps, but VO does not produce deep traps although Bi-6p orbitals are also forming strong σ bonding. This difference is attributed to the difference of the energy level of CBM. In both cases, the CBM consists of Bi-6p orbitals extending into the Cl layers. However, these orbitals are isolated in BiOCl, but those in Bi4NbO8Cl are bonded with each other between neighboring [Bi2O2]2+ layers. This unique bonding-based CBM prevents the formation of deep electron traps, and significantly enhances H2 evolution activity by prolonging the lifetime of highly reactive free electrons. No potential conflict of interest relevant to this article was reported.

British Editorial Society of Bone & Joint Surgery Acta Medica Okayama 2633-1462 6 8 2025 Long-term functional and quality of life outcomes after cementless minimally invasive extendable endoprosthesis replacement in skeletally immature patients with bone sarcomas at the lower limb a Japanese Musculoskeletal Oncology Group (JMOG) study 954 963 EN Yusuke Tsuda Department of Orthopaedic Surgery, The University of Tokyo Hospital Yoshihiro Nishida Department of Rehabilitation, Nagoya University Hospital Akio Sakamoto Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University Koichi Ogura Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tetsuya Sekita Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital Hirotaka Kawano Department of Orthopaedic Surgery, Teikyo University School of Medicine Hiroshi Kobayashi Department of Orthopaedic Surgery, The University of Tokyo Hospital Aims Extendable endoprostheses are utilized to reconstruct segmental defects following resection of bone sarcomas in skeletally immature children. However, there remains a paucity of data regarding long-term functional and quality of life outcomes. Methods We conducted a retrospective, multicentre study and reviewed 45 children who underwent cementless minimally invasive extendable endoprosthetic replacement. Anatomical sites included the distal femur (n = 29), proximal femur (n = 4), proximal tibia (n = 11), and total femur (n = 1). The mean follow-up period was 12 years. The mean age at extendable endoprosthetic replacement was ten years (5 to 15). Most patients (96%, 43/45) had reached skeletal maturity at the final follow-up. Results The ten-year endoprosthetic failure-free survival rate was 60%. Of the 45 patients, 25 (56%) had 42 complications which were frequently related to structural failure (45%, 19/42), with extension mechanism jamming being the most common (n = 7, 17%). Excluding lengthening procedures, 20 patients (44%) underwent additional surgery with a mean of two surgeries per patient. The mean limb-length discrepancy at the final follow-up was 2.3 cm. Limb salvage was achieved in 44 (98%) patients. The mean Musculoskeletal Tumor Society (MSTS) scores, Toronto Extremity Salvage Score (TESS), and EuroQol five-dimension five-level questionnaire (EQ-5D-5L) were 78%, 92%, and 92% at the last follow-up, respectively. Multiple additional surgeries (≥ 2 times) for complications were associated with worse MSTS scores compared with those without multiple additional surgeries (p = 0.009). Moreover, limb-length discrepancy > 3 cm showed significantly worse MSTS scores compared with those ≤ 3 cm (p = 0.019). Conclusion Extendable endoprostheses were associated with a high complication rate and need for additional surgeries over time, especially for structural-related complications. Despite this, successful limb salvage with reasonable function/quality of life and small limb-length discrepancy were achievable in the long term. Patients’ function in the long term depended on the experience of postoperative complications and limb-length discrepancy. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1349-0079 68 1 2026 Dynamin 2 is involved in osteoblast migration by regulating the organization of F-actin 100720 EN Takumi Moriya Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University A. Surong Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nanami Tatsumi Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Yamada Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumiko Takemoto Department of Orthodontics, Okayama University Hospital Hiroshi Kamioka Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirohiko Okamura Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mika Ikegame Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: Dynamin, a GTPase that regulates membrane dynamics, has recently been implicated in actin cytoskeletal remodeling. This study aimed to elucidate the role of dynamin in osteoblast migration by examining the effects of dynamin inhibition on the localization and organization of F-actin and dynamin 2 in MC3T3-E1 cells. Methods: MC3T3-E1 cells were treated with dynamin inhibitors (Dyngo 4a and Dynole 34-2), and cell migration was assessed using a wound-healing assay. Fluorescent staining was performed to analyze the intracellular localization of F-actin and dynamin 2. Results: Dynamin inhibition significantly reduced the migration of MC3T3-E1 cells. Fluorescence analysis revealed a marked decrease in the accumulation and colocalization of F-actin and dynamin 2 at the protrusion edge. Additionally, dynamin inhibition suppressed the formation of lamellipodia and stress fibers while promoting the appearance of abnormal F-actin clusters in the cytoplasm. Conclusions: These findings suggest that dynamin plays an essential role in osteoblast migration by regulating actin cytoskeletal remodeling, particularly through the formation of lamellipodia and stress fibers. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 26 19 2025 Critical Requirement of Senescence-Associated CCN3 Expression in CD44-Positive Stem Cells for Osteoarthritis Progression 9630 EN Janvier Habumugisha Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuichiro Okuda Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Hirose Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Miho Kuwahara Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ziyi Wang Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuaki Ono Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Kamioka Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Kubota Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takako Hattori Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage breakdown, synovial inflammation, and subchondral bone remodeling. Previous studies have shown that cellular communication network factor 3 (CCN3) expression increases with age in cartilage, and its overexpression promotes OA-like changes by inducing senescence-associated secretory phenotypes. This study aimed to investigate the effect of Ccn3 knockout (KO) on OA development using a murine OA model. Destabilization of the medial meniscus (DMM) surgery was performed in wild-type (WT) and Ccn3-KO mice. Histological scoring and staining were used to assess cartilage degeneration and proteoglycan loss. Gene and protein expressions of catabolic enzyme (Mmp9), hypertrophic chondrocyte marker (Col10a1), senescence marker, and cyclin-dependent kinase inhibitor 1A (Cdkn1a) were evaluated. Single-cell RNA sequencing (scRNA-seq) data from WT and Sox9-deficient cartilage were reanalyzed to identify Ccn3+ progenitor populations. Immunofluorescence staining assessed CD44 and Ki67 expression in articular cartilage. The effects of Ccn3 knockdown on IL-1β-induced Mmp13 and Adamts5 expression in chondrocytes were examined in vitro. Ccn3 KO mice exhibited reduced cartilage degradation and catabolic gene expression compared with WT mice post-DMM. scRNA-seq revealed enriched Ccn3-Cd44 double-positive cells in osteoblast progenitor, synovial mesenchymal stem cell, and mesenchymal stem cell clusters. Immunofluorescence showed increased CCN3+/CD44+ cells in femoral and tibial cartilage and meniscus. Ki67+ cells were significantly increased in DMM-treated Ccn3 KO cartilage, mostly CD44+. In vitro Ccn3 knockdown attenuated IL-1β-induced Mmp13 and Adamts5 expressions in chondrocytes. Ccn3 contributes to OA pathogenesis by promoting matrix degradation, inducing hypertrophic changes, and restricting progenitor cell proliferation, highlighting Ccn3 as a potential therapeutic target for OA. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 1349-0079 68 1 2026 Evaluation of Mycobacterium-derived plasmids for application in oral Actinomyces species 100718 EN Sakiko Ohara Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yijuan Sheng Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Nishiya Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ikue Tosa Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuki Takebe Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Arimura Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Mese Department of Dentistry and Oral Surgery, Fukuyama City Hospital Naoko Ohara Department of Operative Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoya Ohara Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objectives: Genetic manipulation tools are essential for elucidating the pathogenic mechanisms of microorganisms. Several species of Actinomyces, including A. israelii, are present in the oral cavity and they are the causative agents of actinomycosis. However, efficient gene-editing tools for these species have not yet been developed. In this study, the aim was to evaluate the introduction of foreign genes into Actinomyces using plasmids derived from Mycobacterium, which belong to the same class as Actinomycetes. Methods: A truncated derivative of pYT923, pYT923S, which contains the replication origin of the M. scrofulaceum plasmid pMSC262 was constructed and introduced into A. israelii by electrotransformation. Results: pYT923S was successfully introduced into A. israelii. The transformation efficiency of A. israelii was approximately 7–66 CFU/μg of DNA, and all transformed colonies harbored pYT923S. The plasmid recovered from A. israelii replicated in Escherichia coli. Conclusions: pYT923S was introduced into and maintained within A. israelii. Therefore, the pYT923S vector represents a useful genetic tool for Actinomyces and it is expected to facilitate future studies on the biology and pathogenicity of Actinomyces. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2040-1116 16 6 2025 Relation between obesity and health disorders as revealed by the J-ORBIT clinical information collection system directly linked to electronic medical records (J-ORBIT 1) 1100 1111 EN Seiji Nishikage Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Yushi Hirota Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Yasushi Nakagawa Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Masamichi Ishii Center for Medical Informatics Intelligence, National Center for Global Health and Medicine Mitsuru Ohsugi Diabetes and Metabolism Information Center, Research Institute, National Center for Global Health and Medicine Eiichi Maeda Division of Medical Informatics, Department of Internal Medicine, Kobe University Graduate School of Medicine Kai Yoshimura Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Akane Yamamoto Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Tomofumi Takayoshi Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Takehiro Kato Department of Diabetes, Endocrinology, and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine Daisuke Yabe Department of Diabetes, Endocrinology, and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine Munehide Matsuhisa Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University Jun Eguchi 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 Yukihiro Fujita Department of Medicine, Shiga University of Medical Science Shinji Kume Department of Medicine, Shiga University of Medical Science Hiroshi Maegawa Department of Medicine, Shiga University of Medical Science Kana Miyake Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine Nobuhiro Shojima Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine Toshimasa Yamauchi Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine Koutaro Yokote Chiba University Kohjiro Ueki Diabetes Research Center, Research Institute, National Center for Global Health and Medicine Kengo Miyo Center for Medical Informatics Intelligence, National Center for Global Health and Medicine Wataru Ogawa Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine Aims/Introduction: Obesity triggers various health disorders, but information on these disorders in real-world settings remains limited. To address this knowledge gap, we developed a database directly linked to electronic medical records (EMRs). We here present the baseline data for this database, designated Japan Obesity Research Based on electronIc healTh Records (J-ORBIT). Materials and Methods: Individuals with obesity disease diagnosed according to the criteria of the Japan Society for the Study of Obesity were registered in J-ORBIT from seven medical centers in Japan. We analyzed the relationship between body mass index (BMI), clinical characteristics, and the prevalence of obesity-related health disorders in this cohort. Results: Data were obtained from 1,169 individuals, with a mean (±SD) age of 56.9 ± 15.3 years and a BMI of 31.4 ± 6.1 kg/m2. The prevalence of health disorders varied substantially across BMI categories, with a higher BMI being associated with an increased prevalence of hyperuricemia or gout, obstructive sleep apnea syndrome or obesity hypoventilation syndrome, musculoskeletal disorders, and obesity-related kidney disease, as well as with a higher frequency of both a family history of obesity and of a history of childhood obesity. Among individuals with a BMI of ≥25 kg/m2, the prevalence of hypertension and dyslipidemia did not increase with BMI, whereas that of glucose intolerance decreased with increasing BMI. Conclusions: The J-ORBIT system, which collects clinical data in real time directly from EMRs, has the potential to provide insight into obesity and its associated health conditions, thereby contributing to improved care of affected individuals. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0929-1903 2025 p53-armed oncolytic adenovirus induces apoptosis in pancreatic cancer-associated stellate cells via macropinocytosis EN Takeyoshi Nishiyama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Nagai 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 Yoshinori Kajiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoyuki Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Takahashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Ohara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyoshi Y. Tanaka Department of Pharmaceutical Biomedicine, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems Mitsunobu R. Kano Department of Pharmaceutical Biomedicine, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems Atsushi Masamune Division of Gastroenterology, Tohoku University Graduate School of Medicine Yasuo Urata Oncolys BioPharma, Inc. Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pancreatic ductal adenocarcinoma (PDAC)-associated pancreatic stellate cells (PSCs) promote PDAC tumor progression. Notably, PDAC tumors display enhanced macropinocytosis, resulting in enhanced uptake of extracellular particles, including nutrients and viruses. We previously demonstrated the therapeutic potential of telomerase-specific oncolytic adenoviruses OBP-301 and p53-armed OBP-702 against human PDAC cells. However, it remains unclear whether macropinocytosis promotes the virus sensitivity of PDAC-associated PSCs. Here, we show that PSCs activated by human PDAC cells (Panc-1 and BxPC-3) exhibit enhanced sensitivity to wild-type and oncolytic adenoviruses via enhanced macropinocytosis. The virus sensitivity of PSCs was analyzed for the infectivity, replication, and cytopathic activity of wild-type and oncolytic adenoviruses. PDAC-associated PSCs were more sensitive to wild-type and oncolytic adenoviruses than were control PSCs; this sensitivity was mediated by activation of macropinocytosis. In three-dimensional (3D) culture models, p53-armed OBP-702 decreased the viability of PDAC-associated PSCs more strongly than did non-armed OBP-301, reflecting induction of p53-mediated apoptosis. Co-inoculation of PSCs enhanced the growth of PDAC tumors, an effect that was attenuated by OBP-702-mediated p53 activation in the tumor stroma. Our results suggest that p53-armed oncolytic adenovirus OBP-702 eliminates PDAC-associated PSCs via enhancement of macropinocytosis-mediated virus entry and induction of p53-mediated apoptosis. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2253 25 1 2025 Clinical predictors of extubation failure in postoperative critically ill patients: a post-hoc analysis of a multicenter prospective observational study 127 EN Jun Hattori Faculty of Medicine, Osaka University Aiko Tanaka Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine Junko Kosaka Department of Anesthesiology and Resuscitology, Okayama University Hospital Osamu Hirao Department of Anesthesiology, Osaka General Medical Center Nana Furushima Department of Anesthesiology and Intensive Care Medicine, Kobe University Hospital Yuichi Maki Department of Anesthesiology, Toho University Ohashi Medical Center Daijiro Kabata Center for Mathematical and Data Science, Kobe University Akinori Uchiyama Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine Moritoki Egi Department of Anesthesia, Kyoto University Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Hospital Satoshi Mizobuchi Department of Anesthesiology and Intensive Care Medicine, Kobe University Hospital Yoshifumi Kotake Department of Anesthesiology, Toho University Ohashi Medical Center Ayumi Shintani Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University Yukiko Koyama Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine Takeshi Yoshida Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine Yuji Fujino Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine Background Postoperative patients constitute majority of critically ill patients, although factors predicting extubation failure in this group of patients remain unidentified. Aiming to propose clinical predictors of reintubation in postoperative patients, we conducted a post-hoc analysis of a multicenter prospective observational study. Methods This study included postoperative critically ill patients who underwent mechanical ventilation for > 24 h and were extubated after a successful 30-min spontaneous breathing trial. The primary outcome was reintubation within 48 h after extubation, and clinical predictors for reintubation were investigated using logistic regression analyses. Results Among the 355 included patients, 10.7% required reintubation. Multivariable logistic regression identified that the number of endotracheal suctioning episodes during the 24 h before extubation and underlying respiratory disease or pneumonia occurrence were significantly associated with reintubation (adjusted odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05–1.18, p < 0.001; adjusted OR 2.58, 95%CI 1.30–5.13, p = 0.007). The probability of reintubation was increased significantly with the higher frequency of endotracheal suctioning, as indicated by restricted cubic splines. Subgroup analysis showed that these predictors were consistently associated with reintubation regardless of the use of noninvasive respiratory support after extubation. Conclusions Endotracheal suctioning frequency and respiratory complications were identified as independent predictors of reintubation. These readily obtainable predictors may aid in decision-making regarding the extubation of postoperative patients. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0276-3478 2025 DSOK-0011 Potentially Regulates Circadian Misalignment and Affects Gut Microbiota Composition in Activity-Based Anorexia Model EN Hiroki Kawai Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nanami Wada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Sakamoto Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Miyazaki Sumitomo Pharma Co. Ltd Taro Kato Sumitomo Pharma Co. Ltd Yoshihiro Horiuchi Sumitomo Pharma Co. Ltd Hiroshi Kirii Department of Animal Applied Microbiology, Okayama University Graduate School of Environmental, Life, Natural Science and Technology Hoang Duy Nguyen Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Hinotsu Department of Neuropsychiatry, Okayama University Hospital Yoshio Ohya Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Asada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiyoshi Yokode Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Okahisa Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruko Miyazaki Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshitaka Oohashi Department of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Objective: Anorexia nervosa (AN) is a metabolic-psychiatric disorder characterized by severe weight loss, hypercortisolemia, and hypothalamic–pituitary–adrenal (HPA) axis activation. In this study, we investigated the effect of inhibiting cortisol regeneration via the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) on the pathophysiology of AN. Method: Female C57BL/6J mice underwent a 7-day activity-based anorexia (ABA) paradigm, involving 3 h daily feeding and free access to wheels, until 25% body weight loss or experiment completion. Mice were orally treated once daily with a potent 11β-HSD1 inhibitor, DSOK-0011, or vehicle. Body weight, food intake, and activity transitions were recorded; plasma corticosterone and cholesterol levels were measured using a fluorometric assay; gut microbiota were analyzed using 16S rRNA sequencing; and hippocampal glial cells were analyzed using immunohistochemistry. Results: DSOK-0011-treated mice exhibited a modest but significant increase in postprandial wheel-running activity compared to baseline (4–5 p.m., p = 0.018; 5–6 p.m., p = 0.043), whereas vehicle-treated mice showed higher preprandial activity (9–10 a.m., p = 0.0229). Gut microbiota analysis revealed increased alpha diversity in ABA mice, with a specific enrichment of the Lachnospiraceae family in the DSOK-0011 group. However, DSOK-0011 did not significantly affect body weight, food intake, corticosterone, and lipid levels, or hippocampal glial cell populations. Conclusion: Inhibition of 11β-HSD1 by DSOK-0011 was associated with microbiota alterations and subtle shifts in activity timing under energy-deficient conditions. These findings suggest that peripheral glucocorticoid metabolism may influence microbial and behavioral responses in the ABA model, although its metabolic impact appears limited in the acute phase. No potential conflict of interest relevant to this article was reported.

Spandidos Publications Acta Medica Okayama 1791-2997 33 1 2025 Protective impact of landiolol against acute lung injury following hemorrhagic shock and resuscitation in rats 22 EN Risa Sakamoto Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroko Shimizu Department of Anesthesiology and Resuscitology, Okayama University Medical School Ryu Nakamura Department of Anesthesiology and Resuscitology, Okayama University Medical School Yifu Lu Department of Human Anatomy, Shantou University Medical College Yaqiang Li Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Emiko Omori Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Takahashi Department of Anesthesiology, Okayama Saidaiji Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hemorrhagic shock and resuscitation (HSR) induces pulmonary inflammation, leading to acute lung injury (ALI). Notably, blocking β1 receptors can lead to organ protection through anti‑inflammatory and anti‑apoptotic effects. Additionally, although the β1 receptor pathway is blocked by the β1 blocker, the β2 receptor pathway may be preserved and activate the 5' adenosine monophosphate‑activated protein kinase (AMPK) pathway. The present study aimed to examine whether administration of the β1 blocker landiolol could achieve lung protection in a model of HSR‑ALI, alongside improvements in inflammation and apoptosis. Male Sprague‑Dawley rats underwent hemorrhage keeping their mean arterial pressure at 30 mmHg for 1 h. Resuscitation by reinfusion was initiated to restore blood pressure to pre‑hemorrhage levels for >15 min, followed by a 45‑min stabilization period to create the HSR‑ALI model. Landiolol (100 mg/kg/min) or saline was continuously administered after resuscitation. The lung tissues, which were collected for assessing inflammation and apoptosis‑related damage, underwent analyses, including histological examination, neutrophil count, assessment of lung wet/dry weight ratio, detection of the mRNA levels of tumor necrosis factor‑α (TNF‑α) and inducible nitric oxide synthase (iNOS), identification of terminal deoxynucleotidyl transferase dUTP nick‑end labeling (TUNEL)‑positive cells, and evaluation of caspase‑3 expression. In addition, phosphorylated AMPKα (pAMPKα) expression was tested via western blotting. Compared with the HSR/saline group, the HSR/landiolol group demonstrated a reduction in lung tissue damage score, and significant reductions in neutrophil count, lung wet/dry weight ratio, lung TNF‑α and iNOS mRNA levels, TUNEL‑positive cells and cleaved caspase‑3 expression. Furthermore, landiolol administration following HSR treatment increased pAMPKα expression. No significant hypotension occurred between the HSR/landiolol and HSR/saline groups; and blood loss did not differ significantly between the groups. In conclusion, landiolol administration after HSR reduced lung inflammation and apoptosis, suggesting a potential improvement in tissue damage. Furthermore, pAMPKα activation in the HSR/landiolol group may be the mechanism underlying the pulmonary protective effects of landiolol. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2363-9024 11 1 2025 Venous air embolism induced by burr hole drilling before dural incision in craniotomy: two case reports 59 EN Yohei Motoi Department of Anesthesiology and Resuscitology, Okayama University Hospital Shuji Okahara Department of Anesthesiology and Resuscitology, Okayama University Hospital Makiko Tani Department of Anesthesiology and Resuscitology, Okayama University Hospital Nobushige Tsuboi Department of Neurosurgery, Okayama Red Cross Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Hospital Background: Venous air embolism (VAE) is a rare but potentially fatal complication in neurosurgery typically caused by injury to dura mater, especially venous sinuses, during craniotomy. We report two cases of VAE that occurred before dural incision. Case presentation: Both patients underwent craniotomy under general anesthesia in a head-up position. Hemodynamic and respiratory deterioration occurred during or immediately after burr hole drilling with abnormal vital signs and transesophageal echocardiography findings, raising suspicion for VAE. Immediate management, including surgical field protection and cardiopulmonary support, stabilized the patients’ conditions. The procedure was subsequently discontinued in case 1 and modified to limited resection in case 2. Postoperative computed tomography revealed intracranial venous air within the internal jugular vein, cavernous sinus, and diploic veins. Conclusion: These cases highlight that VAE can occur even before dural incision. Vigilant intraoperative monitoring and prompt intervention are essential for preventing potentially fatal outcomes. No potential conflict of interest relevant to this article was reported.

S. Karger AG Acta Medica Okayama 0253-5068 2025 Current Status of Continuous Renal Replacement Therapy in Japanese Intensive Care Units: A Multicenter Retrospective Observational Study EN Hidehiko Nakano Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital Ryota Inokuchi Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital Yutaro Inoue Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital Motohiro Sekino Department of Anesthesiology and Intensive Care Medicine, Nagasaki University Graduate School of Biomedical Sciences Yasuyuki Kakihana Department of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences Noriyuki Hattori Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine Mariko Miyazaki Department of Nephrology, Tohoku University Hospital Natsuko Tokuhira Department of Intensive Care, Osaka University Hospital Shigeki Fujitani Department of Emergency and Critical Care Medicine, St. Marianna University School of Medicine Yuichiro Toda Department of Anesthesiology and Intensive Care Medicine, Kawasaki Medical School Yoshifumi Ohchi Department of Anesthesiology and Intensive Care, Oita University Faculty of Medicine Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shingo Ichiba Department of Intensive Care Medicine, Tokyo Women’s Medical University Yoshiki Masuda Department of Intensive Care Medicine, Sapporo Medical University School of Medicine Osamu Nishida Department of Anesthesiology and Critical Care Medicine, School of Medicine, Fujita Health University Takaya Abe Department of Urology, Iwate Medical University Takeshi Moriguchi Department of Emergency and Critical Care Medicine, University of Yamanashi Graduate School of Medicine Kasumi Satoh Department of Emergency and Critical Care Medicine, Akita University Graduate School of Medicine Masafumi Idei Department of Intensive Care Medicine, Yokohama City University Hiromasa Nagata Department of Anesthesiology, Keio University School of Medicine Kent Doi Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital Introduction: Continuous renal replacement therapy (CRRT) is often performed for critically ill patients in intensive care units (ICUs), but its optimal indication and settings have yet to be determined. Thus, we aimed to describe the current status of CRRT in Japan through a multicenter retrospective observational study. Methods: Adult ICU patients receiving CRRT at 18 tertiary hospitals in Japan (up to 100 patients from each hospital over the past year) were retrospectively enrolled. Patients receiving CRRT for <24 h or intermittent renal replacement therapy together with CRRT were excluded. The primary outcomes were the temporal changes in the electrolyte levels, acid-base balance, and uremia-related small solute concentrations. The secondary outcomes included potassium (K) and phosphate (P) supplementations during CRRT. Results: Altogether, 1,045 patients were enrolled. The median CRRT duration and dose were 4.4 days and 17.3 mL/kg/h, respectively. The electrolyte levels, acid-base balance, and uremia-related small solute concentrations returned to normal by day 4 of treatment. A total of 732 (70.0%) patients received K supplementation, and only a few patients had hypokalemia until day 5. Moreover, 414 (39.6%) patients received P supplementation, and approximately 30%–50% of the patients had hypophosphatemia until day 5. Conclusion: The CRRT dose in Japan was lower than that was recommended by the Kidney Disease: Improving Global Outcomes guideline. The electrolyte level abnormalities and acid-base imbalances of the studied patients were improved within 72–96 h of CRRT. Contrarily, K and P supplementations were common, indicating that the current CRRT solutions need to be modified. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0913-8668 39 2 2025 T2 high-signal-intensity zone of the spinal cord dorsal horn in patients treated with spinal cord stimulation for herpes zoster-associated pain: a retrospective case–control study 273 281 EN Kyosuke Arakawa Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masayuki Nakagawa Department of Pain Management Clinic, NTT Medical Center Tokyo Yoichiro Abe Department of Pain Management Clinic, NTT Medical Center Tokyo Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose In patients with herpes zoster-associated pain (ZAP), magnetic resonance imaging (MRI) has revealed T2 high-signal intensity zones (MRI T2 HIZ) in the dorsal horn of the spinal cord, associated with postherpetic neuralgia (PHN). We retrospectively analyzed the relationship between PHN and MRI T2 HIZ in patients with refractory ZAP in the subacute phase who underwent temporary spinal cord stimulation therapy (tSCS). Methods This single-center, case–control study included patients who underwent tSCS for refractory ZAP between 2010 and 2018. MRIs were re-assessed for the presence of T2 HIZ in the dorsal horn of the spinal cord. Patients were divided into T2 HIZ( +) and T2 HIZ(－) groups. Patients with a numerical rating score (NRS) ≥ 3 at the last visit were defined as PHN. The NRS values and the incidence rate of PHN were compared between the two groups. Results Of the 67 cases extracted, 38 were included in the analysis: 22 in T2 HIZ( +) group and 16 in T2 HIZ(－) group. No significant differences were observed in background factors between the two groups. However, the T2 HIZ( +) group had a significantly higher NRS at the final visit (T2 HIZ( +):3.8 ± 2.1, T2 HIZ(－):1.4 ± 1.5; P < 0.05) and had significantly more patients with PHN than the T2 HIZ(－) group (T2 HIZ( +) vs. T2 HIZ(－), 15/22 (68%) vs. 3/16 (19%); odds ratio = 8.67; 95% confidence interval, 1.7–63.3). Conclusion T2HIZ is detected in more than half of refractory ZAP, and pain is more likely to remain after tSCS treatment in the T2HIZ( +) group. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2253 24 1 2024 Efficacy of Pericapsular Nerve Group (PENG) block in preoperative rehabilitation (Prehabilitation) for patients with femoral neck fractures: study protocol for a randomized, placebo-controlled, double-blinded trial 436 EN Zhuan Jin Department of Anesthesiology and Resuscitology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Daisuke Sugiyama Department of Anesthesiology, Kameda Medical Center Fumiya Higo Department of Rehabilitation, Kameda Medical Center Takahiro Hirata Department of Rehabilitation, Kameda Medical Center Osamu Kobayashi Department of Anesthesiology, Kameda Medical Center Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kenichi Ueda Department of Anesthesiology, Kameda Medical Center Background Despite surgery intervention for femoral neck fractures is recommended within 48 h of admission, achieving timely surgery presents challenges for patients with severe comorbidities, or in resource-limited settings. Preoperative rehabilitation (prehabilitation) reduces bedridden time, enhances mobility, and improves postoperative outcomes for patients scheduled for hip arthroplasty due to femoral neck fractures. However, prehabilitation is hindered by insufficient pain control. The pericapsular nerve group (PENG) block provides effective analgesia while preserving motor function. We designed a study to assess the efficacy of PENG block in facilitating prehabilitation for patients with femoral neck fractures who are scheduled for hip arthroplasty. Methods This prospective randomized placebo-controlled double-blinded trial aims to enroll 100 patients with Garden 3 or 4 femoral neck fractures who are scheduled for hip arthroplasty. Participants will be randomly assigned to receive a PENG block with 0.375% ropivacaine (PENG group) or with normal saline (placebo group) before the initial prehabilitation session. The prehabilitation program comprises five items: Bed-sitting, Edge-sitting, Stand-up, Maintaining-standing, and Wheelchair-transfer, performed with the assistance of a single physical therapist. The primary outcome is the percentage of patients completing the entire prehabilitation program. Secondary outcomes during the initial prehabilitation session are the achievement of each program item and the Numerical Rating Scale (NRS) pain score. Other secondary outcomes include intraoperative bleeding amounts, thromboembolic events during postoperative day 0 to 7, postoperative 3-day cumulative Cumulated Ambulation Score (CAS), and discharge destination. The postoperative outcomes will be compared between subgroups of patients undergoing surgery within 48 h of admission and those undergoing surgery more than 48 h of admission. Discussion This is the first study aiming to assess the efficacy of PENG block in prehabilitation for patients with femoral neck fractures who are scheduled for hip arthroplasty. PENG block could be beneficial, especially for patients facing delayed surgery, providing a potential treatment option during the waiting period. Trial registration Japan Registry of Clinical Trials, jRCT1031220294, registered on August 26, 2022. No potential conflict of interest relevant to this article was reported.

The Korean Society of Anesthesiologists Acta Medica Okayama 2005-6419 77 5 2024 Utilization of the pericapsular nerve group block in preoperative rehabilitation of patients with femoral neck fractures -a case series- 565 569 EN Zhuan Jin Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Sugiyama Department of Anesthesiology, Kameda Medical Center Fumiya Higo Department of Rehabilitation, Kameda Medical Center Takahiro Hirata Department of Rehabilitation, Kameda Medical Center Osamu Kobayashi Department of Anesthesiology, Kameda Medical Center Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenichi Ueda Department of Anesthesiology, Kameda Medical Center Background: Elderly patients with femoral neck fractures, particularly those with severe comorbidities or living in regions with limited medical resources, may experience delays in surgical treatment. Although the benefits of preoperative rehabilitation (prehabilitation) in hip arthroplasty have been reported, pain management remains a challenge. The pericapsular nerve group (PENG) block, known for its exceptional analgesic effect and motor function preservation, may be a promising intervention during prehabilitation in these patients. Case: We enrolled ten patients with Garden classification 3–4 femoral neck fractures scheduled for hip arthroplasty. After receiving a PENG block with 20 ml of 0.375% ropivacaine, all patients underwent initial prehabilitation sessions comprising 9 mobility levels, ranging from bed-sitting to walking. One patient was excluded due to experiencing high blood pressure during prehabilitation. Six of the nine remaining patients (66.7%) were successfully transferred from bed to wheelchair. Conclusions: The PENG block enhanced prehabilitation for patients with femoral neck fractures undergoing hip arthroplasty. 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 Serum extracellular vesicles containing adenoviral E1A-DNA as a predictive biomarker for liquid biopsy in oncolytic adenovirus therapy 38590 EN Chiaki Yagi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shinji Kuroda Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunya Hanzawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Daisuke Kadowaki Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yusuke Yoshida Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masaki Sakamoto Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuki Hamada Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ryoma Sugimoto Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tomoko Ohtani Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kento Kumon Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masashi Hashimoto Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Nobuhiko Kanaya Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Satoru Kikuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunsuke Kagawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hiroshi Tazawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuo Urata Oncolys BioPharma, Inc. Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Oncolytic adenoviruses replicate selectively in tumor cells and induce immunogenic cell death, but predictive biomarkers for early therapeutic response are lacking. This study evaluated extracellular vesicle-encapsulated adenoviral E1A-DNA (EV-E1A-DNA) as a minimally invasive biomarker for monitoring responses to telomerase-specific oncolytic adenoviruses OBP-301 and OBP-502. EVs were isolated from human and murine cancer cell lines and from the serum of treated mice using ultracentrifugation. EV-associated E1A-DNA levels were measured by quantitative polymerase chain reaction and found to correlate with cytotoxicity in vitro and tumor regression in vivo. In xenograft models, serum EV-E1A-DNA levels at 2 days post-treatment showed strong correlations with final tumor volume and survival, supporting their utility as an early predictive biomarker. In immunocompetent mice pre-immunized with wild-type adenovirus, free viral DNA was undetectable in serum due to neutralizing antibodies, whereas EV-E1A-DNA remained detectable. This “stealth effect” indicates that EVs protect viral components from immune clearance. These results demonstrate that EV-E1A-DNA is a sensitive and virus-specific biomarker that enables early assessment of therapeutic efficacy, even in the presence of antiviral immunity. This strategy offers a promising liquid biopsy approach for personalized monitoring of oncolytic virotherapy and may be applicable to other virus-based therapies. No potential conflict of interest relevant to this article was reported.

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

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

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

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

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 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.

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

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

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

Springer Science and Business Media LLC Acta Medica Okayama 1757-6512 16 1 2025 Specific induction of right ventricular-like cardiomyocytes from human pluripotent stem cells 519 EN Yukihiro Saito Department of Cardiovascular Medicine, Okayama University Hospital Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Hospital Yuki Katanosaka Department of Cardiovascular Physiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Toshihiro Iida Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Dai Kusumoto Department of Biomedical Informatics and Molecular Biology, The Sakaguchi Laboratory, Keio University School of Medicine Ryushi Sato Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka Riki Adachi Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka Satoshi Shimizu Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka Junko Kurokawa Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Masashi Yoshida Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Keiji Naruse Department of Cardiovascular Physiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Mikako Nishida Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Heiichiro Udono Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Jianhua Zhang Department of Medicine, University of Wisconsin School of Medicine and Public Health Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Timothy J. Kamp Department of Medicine, University of Wisconsin School of Medicine and Public Health Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Background Applications employing human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) require well-characterized, chamber-specific hPSC-CMs. Distinct first heart field (FHF) and second heart field (SHF) cardiac progenitor populations give rise to the left ventricular (LV) and right ventricular (RV) cardiomyocytes, respectively. This developmental difference in cardiomyocyte origin suggests that chamber-specific cardiomyocytes have unique characteristics. Therefore, efficient strategies to differentiate human pluripotent stem cells (hPSCs) specifically to LV-like or RV-like cardiomyocytes are needed and it is still unknown whether there is a phenotypic difference between LV-like cardiomyocytes and RV-like cardiomyocytes derived from hPSCs. Methods An established hPSC cardiac differentiation protocol employing sequential GSK3β inhibition followed by Wnt inhibition (GiWi) was modified by addition of insulin or BMP antagonists during mesoderm formation. Cardiac progenitor populations were evaluated for FHF and SHF markers, and differentiated hPSC-CMs were characterized for chamber-specific markers. Results The GiWi protocol produced mainly FHF-like progenitor cells that gave rise to LV-like cardiomyocytes. Inhibition of endogenous BMP signaling during mesoderm induction using insulin or BMP antagonists reduced expression of FHF markers and increased expression of SHF markers in cardiac progenitor cells. hPSC-CMs arising from the SHF-like progenitor cells showed an RV-like gene expression pattern and exhibited phenotypic differences in spontaneous contraction rate, Ca2+ transients, and cell size compared to control LV-like cardiomyocytes. Conclusion This study establishes methodology to generate RV-like hPSC-CMs to support the development of disease modeling research using chamber-specific hPSC-CMs. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 1936-5209 19 3 2025 Oregon Wolfe barley genetic stocks – Research and teaching tools for next generation scientists e70004 EN Margaret R. Krause Department of Crop and Soil Science, Oregon State University Juan David Arbelaez Department of Crop Sciences, University of Illinois at Urbana-Champaign Åsmund Asdal Nordic Genetic Resource Centre Ramzi Belkodja CIHEAM-Zaragoza Nancy Boury Department of Plant Pathology, Entomology, and Microbiology, Iowa State University Victoria C. Blake Department of Plant Sciences and Plant Pathology, Montana State University Patrick J. Brown Department of Plant Sciences, University of California-Davis Ana Casas Departamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSIC Luis Cistué Departamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSIC Alba Farré‐Martínez AGROTECNIO-CERCA Center, Universidad de Lleida Scott Fisk Department of Crop and Soil Science, Oregon State University Gregory S. Fuerst U.S. Department of Agriculture-Agricultural Research Service, Corn Insects and Crop Genetics Research Unit, Iowa State University Estela Giménez Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid Carla Guijarro‐Real Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid Katy Guthrie Department of Agronomy and Plant Genetics, University of Minnesota Margaret Halstead Aardevo North America Laura Helgerson Department of Crop and Soil Science, Oregon State University Hiroshi Hisano Institute of Plant Science and Resources, Okayama University Ernesto Igartua Departamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSIC Morten Lillemo Department of Plant Sciences, Norwegian University of Life Sciences Marina Martínez‐García Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid Mariona Martínez‐Subirà AGROTECNIO-CERCA Center, Universidad de Lleida Susan McCouch Plant Breeding and Genetics Section, School of Integrative Plant Science, Cornell University Laurie McGhee Colfax-Mingo Community High School Travis Nickols Department of Crop and Soil Science, Oregon State University Nick Peters Department of Plant Pathology, Entomology, and Microbiology, Iowa State University Raymond Porter Haupert Institute for Agricultural Studies, Huntington University Ignacio Romagosa AGROTECNIO-CERCA Center, Universidad de Lleida Anja Karine Ruud Department of Plant Sciences, Norwegian University of Life Sciences Kazuhiro Sato Institute of Plant Science and Resources, Okayama University Silvio Salvi Department of Agricultural and Food Sciences, University of Bologna Giuseppe Sangiorgi Department of Agricultural and Food Sciences, University of Bologna Rebekka Schüller Department of Crop Sciences, University of Illinois at Urbana-Champaign Taner Z. Sen Crop Improvement and Genetics Research Unit, U.S. Department of Agriculture-Agricultural Research Service José Miguel Soriano AGROTECNIO-CERCA Center, Universidad de Lleida Robert M. Stupar Department of Agronomy and Plant Genetics, University of Minnesota To‐Chia Ting Agronomy Department, Purdue University Kelly Vining Department of Crop and Soil Science, Oregon State University Maria von Korff Institute of Plant Genetics, Heinrich-Heine-Universität Düsseldorf Agatha Walla Institute of Plant Genetics, Heinrich-Heine-Universität Düsseldorf Diane R. Wang Agronomy Department, Purdue University Robbie Waugh Division of Plant Sciences, School of Life Sciences, University of Dundee Roger P. Wise Department of Plant Pathology, Entomology, and Microbiology, Iowa State University Robert Wolfe Agriculture and Agri-Food Canada Eric Yao Crop Improvement and Genetics Research Unit, U.S. Department of Agriculture-Agricultural Research Service Patrick M. Hayes Department of Crop and Soil Science, Oregon State University The Oregon Wolfe Barley (OWB) mapping population (Reg. no. MP-4, NSL 554937 MAP) is a resource for genetics research and instruction. The OWBs are a set of doubled haploid barley (Hordeum vulgare L.) lines developed at Oregon State University from the F1 of a cross between Dr. Robert Wolfe's dominant and recessive marker stocks. Exhibiting a high level of genetic and phenotypic diversity, the OWBs are used throughout the world as a research tool for barley genetics. To date, these endeavors have led to 56 peer-reviewed publications, as well as three reports in the Barley Genetics Newsletter. At the same time, the OWBs are widely used as an instructor resource at the K–12, undergraduate, graduate, and professional levels. They are currently used at universities and/or institutes in German, Italy, Norway, Spain, and the United States and are currently being developed further for educational use in other countries. Genotype and phenotype data, lesson plans, and seed availability information are available herein and online. No potential conflict of interest relevant to this article was reported.

Elsevier B.V. Acta Medica Okayama 0304-4165 1869 12 2025 The F54L mutation of Thioredoxin shows protein instability and increased fluctuations of the catalytic center 130860 EN Takumi Baba Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center Go Ueno Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center Chika Ohe Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center Shuku Saji Structural Biology Division, Japan Synchrotron Radiation Research Institute Sachiko Yamamoto Structural Biology Division, Japan Synchrotron Radiation Research Institute Masaki Yamamoto Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center Hiroshi Nakagawa Materials Sciences Research Center, Japan Atomic Energy Agency Nobuo Okazaki Neutron Science and Technology Center, Comprehensive Research Organization for Science and Society (CROSS) Mamoru Ouchida Department of Molecular Oncology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Iori Kawasaki-Ohmori Section of Developmental Physiology and Pathology, Faculty of Education, Okayama University Kohei Takeshita Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center Thioredoxin is a ubiquitous redox protein that acts as an electron donor via its conserved dithiol motif (C32GPC35), catalyzing dithiol–disulfide exchange to regulate the redox state of target proteins. It supports antioxidant defense via peroxiredoxins, facilitates DNA synthesis by donating electrons to ribonucleotide reductase, and regulates redox-sensitive signaling pathways, including those controlling transcription and apoptosis. Neuronal degeneration and chronic kidney disease have been observed in Txn-F54L mutant rats; however, the details of why the Txn mutation causes these phenomena remain unknown. The present study aimed to elucidate the functional and structural changes caused by the F54L mutation. The Thioredoxin-F54L showed less insulin-reducing activity and more thermosensitivity to denaturation in the body temperature range compared to the wild type. The crystal structure revealed that F54 forms hydrophobic interactions with the surrounding hydrophobic amino acids. In addition, molecular dynamics simulation predicts increased fluctuations around the F54L mutation and a tendency for the distance between residues C32 and C35 at the catalytic center to be widened. The increased distance between residues C32 and C35 of the catalytic center may affect the reducing activity of the enzyme on the substrate. The finding that Thioredoxin-F54L is prone to denaturation at normal body temperature may reduce the normally functioning Thioredoxin. These molecular characteristics of Thioredoxin-F54L may be related to brain and kidney disease development in the Txn-F54L rats. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0016-7037 400 2025 Lithium- and oxygen-isotope compositions of a Si-rich nebular reservoir determined from chondrule constituents in the Sahara 97103 EH3 chondrite 51 71 EN Torii Douglas-Song The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Tsutomu Ota The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Masahiro Yamanaka The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Hiroshi Kitagawa The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Ryoji Tanaka The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Christian Potiszil The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Tak Kunihiro The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Here we report the in situ ion-microprobe analyses of the Li- and O-isotope compositions of enstatite, FeO-rich pyroxene, olivine, glass, and cristobalite grains from six chondrule-related objects from the Sahara 97103 EH3 chondrite. The O-isotope composition of the enstatite grains scattered around the intersection between the terrestrial fractionation and primitive chondrule minerals lines. Whereas, that of olivine varied along the primitive chondrule minerals line. Based on the mineralogy, we found cristobalite formed as a result of Si saturation, instead of the reduction of FeO-rich silicates, consistent with Si-enrichment of whole rock enstatite chondrites. Based on the mineralogy and O-isotope compositions, we infer that olivines in some chondrules are relict grains. In chondrules that contained olivine, no abundant niningerite [(Mg,Fe,Mn)S] was observed. Thus, enstatite formation can be explained by the interaction of an olivine precursor with additional SiO2 (Mg2SiO4 + SiO2 → Mg2Si2O6), instead of sulfidation (Mg2SiO4 + S → 1/2 Mg2Si2O6 + MgS + 1/2 O2). Using the equation Mg2SiO4 + SiO2 → Mg2Si2O6 and the O-isotope compositions of enstatite and olivine, the O-isotope composition of the additional SiO2 was estimated. Based on the O-isotope composition, we infer that there could be a Si-rich gas with an elevated Δ17O value similar to, or greater than the second trend line (Δ17O = 0.9 ‰) suggested by Weisberg et al. (2021), during chondrule formation. The variation in the Li-isotope compositions of enstatite and olivine grains from EH3 chondrules is smaller than that for the same phases from CV3 chondrules. The variation in the Li-isotope compositions of the enstatite and olivine grains from EH3 chondrules is also smaller than that of their O-isotope compositions. During the recycling of enstatite-chondrite chondrules, both Li- and O-isotope compositions were homogenized. Although enstatite is the major carrier of Li in EH3 chondrules, the Li-isotope composition (δ7Li) of enstatite is lower than that of whole rock EH3 chondrites, suggesting the existence of a phase with higher δ7Li. Meanwhile, the Li-isotope composition and concentration (δ7Li, [Li]) of enstatite is higher than that of olivine. The Li-isotope composition of the Si-rich gas was estimated to be δ7Li = 1 ‰, using a similar mass-balance calculation as applied for the O-isotope composition. The Li-isotope composition of the Si-rich gas from the enstatite-chondrite-chondrule forming-region, is consistent with that of whole rock EH3 chondrites, and differs significantly from that of the Si-rich gas from the carbonaceous-chondrite-chondrule forming-region (δ7Li = －11 ‰) determined by a previous study. We speculate that the Si-rich gas in the carbonaceous-chondrite-chondrule forming-region maintained the Li-isotope heterogeneity inherited from light lithium synthesized by galactic cosmic-ray spallation in the interstellar medium. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1475-2867 25 1 2025 Precise stratification of prognosis in pancreatic ductal adenocarcinoma patients based on pre- and postoperative genomic information 305 EN Kokichi Miyamoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Toshiaki Takahashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Moriwake Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masashi Kayano 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 Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hideki Yamamoto Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mizuki Morita Department of Biomedical Informatics, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate among all cancers; hence, multidisciplinary treatment is essential for patients with PDAC. Although the resectability status, tumour marker, KRAS circulating tumour DNA (mutKRAS-ctDNA) mutations, and GATA binding 6 (GATA6) expression status are promising prognostic biomarkers, their effective integration before and after surgery remains unclear. Methods In this retrospective cohort study, patients with PDAC who had undergone radical resection were enrolled, and pre- and postoperative independent factors associated with poor prognosis were identified using Cox hazard modelling. Risk stratification systems were developed using the identified prognostic factors and investigated for the ability to predict prognosis. Results A total of 91 patients with PDAC were included (median follow-up duration, 28 months). Borderline resectable or locally advanced cancer at diagnosis, elevated carbohydrate antigen 19–9 (CA19-9) level, and mutKRAS-ctDNA-positive status were identified as independent preoperative factors associated with poor prognosis. The postoperative factors significantly associated with shorter overall survival were low GATA6 expression, elevated CA19-9 level, and mutKRAS-ctDNA-positive status. Finally, the preoperative and postoperative risk scoring systems developed using Cox modelling hazard ratio values could significantly stratify prognosis after curative resection for PDAC. Conclusion A risk stratification system based on liquid biopsy, specialised for each phase (pre- and post-surgery), has been proven to be a useful, simple, and practical prognostic prediction clinical tool to determine the optimal multidisciplinary treatment protocol for PDAC. No potential conflict of interest relevant to this article was reported.

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

Oxford University Press (OUP) Acta Medica Okayama 1439-7595 2025 Recommendations for the treatment of juvenile idiopathic arthritis with oligoarthritis or polyarthritis from the 2024 update of the Japan College of Rheumatology Clinical Practice Guidelines for the management of rheumatoid arthritis including juvenile idiopathic arthritis with oligoarthritis or polyarthritis – secondary publication roaf042 EN Takako Miyamae Department of Pediatric Rheumatology, Institute of Rheumatology, Tokyo Women’s Medical University Hospital Nami Okamoto Department of Pediatrics, Osaka Rosai Hospital, Japan Organization of Occupational Health and Safety Yuzaburo Inoue Department of General Medical Science, Graduate School of Medicine, Chiba University Tomohiro Kubota Department of Pediatrics, Kagoshima Prefectural Satsunan Hospital Takasuke Ebato Department of Pediatrics, Kitasato University Hitoshi Irabu Department of Pediatrics and Development Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University Hideto Kameda Division of Rheumatology, Department of Internal Medicine, Toho University Yuko Kaneko Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine Hiroshi Kubo Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kanako Mitsunaga Department of Allergy and Rheumatology, Chiba Children's Hospital Masaaki Mori Department of Lifetime Clinical Immunology, Tokyo Medical and Dental University Ayako Nakajima Center for Rheumatic Diseases, Mie University Hospital Kenichi Nishimura Department of Pediatrics, Yokohama City University Graduate School of Medicine Naoaki Ohkubo Iizuka Hospital Tomomi Sato Clinical Education Center For Physicians, Shiga University of Medical Science Yuko Sugita Department of Pediatrics, School of Medicine, Osaka Medical and Pharmaceutical University Satoshi Takanashi Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine Takayuki Tanaka Department of Pediatrics, Japanese Red Cross Otsu Hospital Hiroaki Umebayashi Department of Rheumatology and Infectious Diseases, Miyagi Children’s Hospital Masato Yashiro Department of Pediatrics, Okayama University Hospital Shingo Yamanishi Department of Pediatrics, Nippon Medical School Mie Fusama Health Sciences Department of Nursing, Kansai University of International Studies Shintaro Hirata Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital Mitsumasa Kishimoto Department of Nephrology and Rheumatology, Kyorin University School of Medicine Masataka Kohno Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Masayo Kojima Graduate School of Medical Sciences, Nagoya City University Toshihisa Kojima Department of Orthopedic Surgery, National Hospital Organization Nagoya Medical Center Akio Morinobu Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University Takahiko Sugihara Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine Eiichi Tanaka Division of Rheumatology, Department of Internal Medicine, School of Medicine, Tokyo Women's Medical University Nobuyuki Yajima Division of Rheumatology, Department of Medicine, Showa University School of Medicine Ryo Yanai Division of Rheumatology, Department of Medicine, Showa University School of Medicine Yutaka Kawahito Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Masayoshi Harigai Division of Rheumatology, Department of Internal Medicine, School of Medicine, Tokyo Women's Medical University Objectives: To conduct systematic reviews (SRs) and develop clinical practice guidelines (CPGs) for managing juvenile idiopathic arthritis (JIA) with oligoarthritis or polyarthritis. Methods: The Grading of Recommendations, Assessment, Development, and Evaluation methodology was employed to carry out SRs and formulate the CPGs. An expert panel, including patients, paediatric and nonpaediatric rheumatologists, guideline specialists, and patient representatives, used the Delphi method to discuss and agree on the recommendations. Results: Six clinical questions (CQs) on the efficacy and safety of medical treatments were evaluated. These included CQ1 on methotrexate (MTX), CQ2 on non-MTX conventional synthetic disease-modifying antirheumatic drugs, CQ3 on glucocorticoids, CQ4 on tumour necrosis factor inhibitors, CQ5 on interleukin-6 inhibitors, and CQ6 on Janus kinase inhibitors. Two randomized controlled trials were identified for CQ1, three for CQ2, two for CQ3, eight for CQ4, two for CQ5, and two for CQ6. Based on these evaluations, three strong and three conditional recommendations were established. The CPGs have been endorsed by the Japan College of Rheumatology and the Pediatric Rheumatology Association of Japan. Conclusions: The SRs provided the necessary evidence to develop the CPGs, which are intended to guide not only paediatric but also nonpaediatric rheumatologists, caregivers, patients, and their families in treatment decision-making. No potential conflict of interest relevant to this article was reported.

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

Walter de Gruyter GmbH Acta Medica Okayama 2081-6936 16 1 2025 Age-related behavioural abnormalities in C57BL/6.KOR–Apoe shl mice EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Eriko Kitano Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Tetsuji Miyazaki Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Spontaneously hyperlipidaemic (Apoeshl) mice were discovered in 1999 as mice lacking apolipoprotein E (ApoE) owing to a mutation in the Apoe gene. However, age-related behavioural changes in commercially available Apoeshl mice have not yet been clarified. The behavioural abnormalities of ApoE-deficient mice, which are genetically modified mice artificially deficient in ApoE, have been investigated in detail, and it has been reported that they can serve as a model of Alzheimer’s disease (AD). To understand whether Apoeshl mice can also serve as a murine model of AD, it is necessary to investigate age-related behavioural abnormalities in Apoeshl mice. In this study, we conducted a series of behavioural experiments on 7- and 11-month-old Apoeshl mice to investigate the behavioural abnormalities associated with ageing in Apoeshl mice. In this study, 7-month-old Apoeshl mice showed decreased body weight and grip strength compared to age-matched wild-type mice. In the open field test, 7-month-old Apoeshl mice showed increased anxiety-like behaviour compared to wild-type mice, whereas 11-month-old Apoeshl mice showed decreased anxiety-like behaviour. Moreover, Apoeshl mice aged 7 and 11 months had increased serum cholesterol levels. These results indicate that the behaviour of Apoeshl mice changes with age. However, 11-month-old Apoeshl mice did not show a decline in cognitive function or memory ability similar to murine models of AD. Our findings indicate that Apoeshl mice can be used to investigate the function of ApoE in the central nervous system. No potential conflict of interest relevant to this article was reported.

Walter de Gruyter GmbH Acta Medica Okayama 2081-6936 16 1 2025 Rearing in an envy-like environment increases anxiety-like behaviour in mice EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Eriko Kitano Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Interest in the societal and psychological harm caused by widespread envy and social comparison is increasing. Envy is associated with anxiety and depression, though the mechanism by which envy affects neuropsychiatric disorders, such as depression, remains unclear. Clarifying the neurobiological basis of envy’s effects on behaviour and emotion regulation in experimental mice is essential for developing disease-prevention and treatment strategies. As mice recognize other mice in neighbouring cages, this study investigated whether they recognize neighbouring cages housed in environmentally enriched cages and suffer psychological stress due to envy. After being raised in an envy-like environment for 3 weeks, we revealed changes in the behaviour of the mice through a series of behavioural experiments. Mice raised in an envious environment showed increased body weight and anxiety-like behaviour but decreased social behaviour and serum corticosterone levels compared to control mice. Thus, mice recognize their neighbouring cages and experience psychological stress due to envy. This study revealed a part of the scientific basis for why envy increased anxiety. Using this novel experimental breeding environment, it may be possible to create an experimental animal model of anxiety disorders. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0953-4180 2024 2024 Mice Recognise Mice in Neighbouring Rearing Cages and Change Their Social Behaviour 9215607 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Mice are social animals that change their behaviour primarily in response to visual, olfactory, and auditory information from conspecifics. Rearing conditions such as cage size and colour are important factors influencing mouse behaviour. In recent years, transparent plastic cages have become standard breeding cages. The advantage of using a transparent cage is that the experimenter can observe the mouse from outside the cage without touching the cage. However, mice may recognise the environment outside the cage and change their behaviour. We speculated that mice housed in transparent cages might recognise mice in neighbouring cages. We used only male mice in this experiment. C57BL/6 mice were kept in transparent rearing cages with open lids, and the cage positions were maintained for 3 weeks. Subsequently, we examined how mice behaved toward cagemate mice, mice from neighbouring cages, and mice from distant cages. We compared the level of interest in mice using a social preference test. Similar to previous reports, subject mice showed a high degree of interest in unfamiliar mice from distant cages. By contrast, subject mice reacted to mice from neighbouring cages as familiar mice, similar to cagemate mice. This suggests that mice housed in transparent cages with open lids perceive the external environment and identify mice in neighbouring cages. Researchers should pay attention to the environment outside the mouse cage, especially for the social preference test. No potential conflict of interest relevant to this article was reported.

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

Oxford University Press (OUP) Acta Medica Okayama 1347-6947 89 8 2025 Microbial biotransformation of proteins into amino acids in unpolished Thai and polished Japanese rice varieties cultivated with distinct industrial strains of koji mold 1217 1226 EN Jirayu Jitpakdee Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazunari Ito Industrial Technology Center of Okayama Prefecture Yuka Tanino Industrial Technology Center of Okayama Prefecture Hayato Takeuchi Industrial Technology Center of Okayama Prefecture Hideyuki Yamashita Higuchi Matsunosuke Shoten Co., Ltd. Takuro Nakagawa Higuchi Matsunosuke Shoten Co., Ltd. Teruhiko Nitoda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroshi Kanzaki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University We previously reported the cultivation of industrial koji mold strains to produce unpolished Thai-colored rice kojis. These kojis, along with those made from unpolished Thai white rice and polished Japanese white rice, showed increased polyphenol content after cultivation, with the highest levels observed in unpolished Thai-colored rice kojis. In this study, an increase in both proteinogenic and non-proteinogenic amino acid contents, particularly γ-aminobutyric acid (GABA) content, was observed in both unpolished Thai and polished Japanese rice kojis, suggesting the ability of koji mold in the biotransformation of proteins. This increase was almost comparable even when using different rice varieties; in contrast, it varied depending on the koji mold strain used. The observed increase in both polyphenol and functional amino acid contents, especially GABA content, highlights the potential of unpolished Thai and polished Japanese rice kojis, particularly unpolished Thai-colored rice koji, as multifunctional materials, benefiting from polyphenol and amino acid functionalities. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 63 23 2024 Successful Treatment for Life Threatening Recurrent Non-traumatic Rectus Sheath Hematoma in a Case with Microscopic Polyangiitis with Rapidly Progressive Glomerulonephritis 3243 3248 EN Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hidemi Takeuchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Shiho Morimoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yuya Terajima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Shugo Okamoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Onishi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Keiko Tanaka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kenji Tsuji 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 Katsuyuki Tanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morinaga Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Mayu Uka Department of Radiology, Okayama University Hospital Koji Tomita Department of Radiology, Okayama University Hospital Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences A 68-year-old woman was admitted to our hospital because of a rapid progression of renal dysfunction with positive myeloperoxidase antineutrophil cytoplasmic antibody and was diagnosed with rapidly progressive glomerulonephritis associated with microscopic polyangiitis (MPA). Severe right rectus sheath hematoma (RSH) bleeding from the inferior epigastric artery developed after starting hemodialysis, which required 4 transarterial embolizations due to recurrent bleeding. After additional treatment with methylprednisolone pulse therapy and rituximab, no rebleeding occurred. Although the giant hematoma reached the pelvis, it shrank spontaneously without any intervention. Nontraumatic RSH should therefore be considered when treating patients with multiple risk factors. 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 Effect of mechanical stretching stimulation on maturation of human iPS cell-derived cardiomyocytes co-cultured with human gingival fibroblasts 30648 EN Mengxue Wang Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Harumi Idei Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chen Wang Department of Nursing, School of Life and Health Sciences, HuZhou College Yin Liang Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yun Liu Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Matsuda Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Takahashi Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Kamioka Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiji Naruse Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University In the realm of regenerative medicine, despite the various techniques available for inducing the differentiation of induced pluripotent stem (iPS) cells into cardiomyocytes, there remains a need to enhance the maturation of the cardiomyocytes. This study aimed to improve the differentiation and subsequent maturation of iPS-derived cardiomyocytes (iPS-CMs) by incorporating mechanical stretching. Human iPS cells were co-cultured with human gingival fibroblasts (HGF) on a polydimethylsiloxane (PDMS) stretch chamber, where mechanical stretching stimulation was applied during the induction of cardiomyocyte differentiation. The maturation of iPS-CMs was assessed using qRT-PCR, immunocytochemistry, transmission electron microscopy, calcium imaging and contractility comparisons. Results indicated significantly elevated gene expression levels of cardiomyocyte markers (cTnT) and the mesodermal marker (Nkx2.5) in the stretch group compared to the control group. Fluorescent immunocytochemical staining revealed the presence of cardiac marker proteins (cTnT and MYL2) in both groups, with higher protein expression in the stretch group. Additionally, structural maturation of iPS-CMs in the stretch group was notably better than in the control group. A significant increase in the contractility and calcium cycle of iPS-CMs was observed in the stretch group. These findings demonstrate that mechanical stretching stimulation enhances the maturation of iPS-CMs co-cultured with HGF. 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. 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). 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. 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. 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.

Springer Science and Business Media LLC Acta Medica Okayama 1758-9193 16 1 2024 Impact of amyloid and tau positivity on longitudinal brain atrophy in cognitively normal individuals 77 EN Motonobu Fujishima Department of Radiology, Kumagaya General Hospital Yohei Kawasaki Department of Biostatistics, Graduate School of Medicine, Saitama Medical University Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Hiroshi Matsuda Department of Biofunctional Imaging, Fukushima Medical University Background Individuals on the preclinical Alzheimer's continuum, particularly those with both amyloid and tau positivity (A + T +), display a rapid cognitive decline and elevated disease progression risk. However, limited studies exist on brain atrophy trajectories within this continuum over extended periods. Methods This study involved 367 ADNI participants grouped based on combinations of amyloid and tau statuses determined through cerebrospinal fluid tests. Using longitudinal MRI scans, brain atrophy was determined according to the whole brain, lateral ventricle, and hippocampal volumes and cortical thickness in AD-signature regions. Cognitive performance was evaluated with the Preclinical Alzheimer's Cognitive Composite (PACC). A generalized linear mixed-effects model was used to examine group × time interactions for these measures. In addition, progression risks to mild cognitive impairment (MCI) or dementia were compared among the groups using Cox proportional hazards models. Results A total of 367 participants (48 A + T + , 86 A + T － , 63 A － T + , and 170 A － T － ; mean age 73.8 years, mean follow-up 5.1 years, and 47.4% men) were included. For the lateral ventricle and PACC score, the A + T － and A + T + groups demonstrated statistically significantly greater volume expansion and cognitive decline over time than the A － T － group (lateral ventricle: β = 0.757 cm3/year [95% confidence interval 0.463 to 1.050], P < .001 for A + T － , and β = 0.889 cm3/year [0.523 to 1.255], P < .001 for A + T + ; PACC: β = － 0.19 /year [－ 0.36 to － 0.02], P = .029 for A + T － , and β = － 0.59 /year [－ 0.80 to － 0.37], P < .001 for A + T +). Notably, the A + T + group exhibited additional brain atrophy including the whole brain (β = － 2.782 cm3/year [－ 4.060 to － 1.504], P < .001), hippocampus (β = － 0.057 cm3/year [－ 0.085 to － 0.029], P < .001), and AD-signature regions (β = － 0.02 mm/year [－ 0.03 to － 0.01], P < .001). Cox proportional hazards models suggested an increased risk of progressing to MCI or dementia in the A + T + group versus the A － T － group (adjusted hazard ratio = 3.35 [1.76 to 6.39]). Conclusions In cognitively normal individuals, A + T + compounds brain atrophy and cognitive deterioration, amplifying the likelihood of disease progression. Therapeutic interventions targeting A + T + individuals could be pivotal in curbing brain atrophy, cognitive decline, and disease progression. No potential conflict of interest relevant to this article was reported.

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

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

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

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

Informa UK Limited Acta Medica Okayama 1179-1322 17 2025 Predictive Value of Tumor ERCC1 Expression for Treatment Outcomes After Adjuvant Chemotherapy in Patients with Completely Resected Non-Small Cell Lung Cancer 1477 1486 EN Masao Nakata Department of General Thoracic Surgery, Kawasaki Medical School Shinsuke Saisho Department of General Thoracic Surgery, Kawasaki Medical School Junichi Soh Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihito Okumura Department of Thoracic Surgery, Kurashiki Central Hospital Hiroshige Nakamura Division of General Thoracic Surgery and Breast and Endocrine Surgery, Department of Surgery, Faculty of Medicine, Tottori University Motohiro Yamashita Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Date Department of Thoracic Surgery, Kyoto University Graduate School of Medicine Purpose: To evaluate the predictive value of tumor expression of the excision repair cross-complementation group 1 gene (ERCC1) for the treatment outcomes after platinum-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer (NSCLC). Methods: In this study, we conducted immunohistochemical analysis using a mouse monoclonal anti-ERCC1 antibody (clone 8F1) of operative specimens obtained from 238 patients enrolled in the SLCG0401 study which compared paclitaxel plus carboplatin (CBDCA+PTX) with uracil-tegafur (UFT) as adjuvant chemotherapy for stage IB-IIIA NSCLC. The overall survival (OS) of the patients was compared according to the ERCC1 expression status and adjuvant chemotherapy employed. Results: Of the 238 specimens, 102 (42.9%) showed a positive result for ERCC1 expression. There were no significant differences in the patient characteristics or OS between the tumor ERCC1-positive and -negative patient groups. Among the patients with ERCC1-negative tumors, there was no significant difference in the survival between patient groups treated with CBDCA+PTX and UFT (HR=0.932, 95% CI: 0.52– 1.67, p=0.814). However, among the patients with ERCC1-positive tumors, CBDCA+PTX treatment tended to yield an inferior outcome, in terms of the OS, as compared with UFT treatment (HR=1.852, 95% CI: 0.92– 3.73, p=0.080). Multivariate analysis showed that ERCC1 expression was not an independent predictor of the OS following CBDCA+PTX treatment in completely resected NSCLC patients. Conclusion: In completely resected NSCLC patients with positive tumor ERCC1 expression, adjuvant CBDCA+PTX treatment tended to yield an inferior outcome as compared with UFT treatment in terms of the OS. However, immunohistochemical analysis with the 8F1 antibody cannot be used for clinical decision making at this point. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1435-2451 409 1 2024 Subjective global assessment for nutritional screening and its impact on surgical outcomes: A prospective study in older patients with colorectal cancer 356 EN Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 Nobuhiko Kanaya 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 Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshitaka Kondo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Tamura Perioperative Management Center, Okayama University Hospital Yoshikazu Matsuoka Perioperative Management Center, Okayama University Hospital Hiroshi Morimatsu Perioperative Management Center, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose Our perioperative management center provides preoperative intervention and functional and nutritional assessments for colorectal cancer patients aged over 75 years. This study evaluated the associations of preoperative nutritional status with postoperative outcomes and prognosis in colorectal cancer patients aged 75 years or older. Methods This was a prospective, observational study of 71 colorectal cancer patients aged 75 years or older who underwent surgery between July 2020 and September 2022. The Subjective Global Assessment (SGA) was evaluated as a nutritional index. The patients were classified into three groups: SGA-A (well nourished), B (moderately malnourished), and C (severely malnourished), and the correlations with postoperative outcomes and prognosis were examined. Results The median age of the 71 patients (34 males, 37 females) was 78 (75–92) years, and their median body mass index (BMI) was 22.3 (13.4–31.9) kg/m2. Forty-eight patients had colon cancer, and 23 had rectal cancer. On the SGA, 28 patients were SGA-A, 25 SGA-B, and 18 SGA-C. The SGA-B/C group had significantly higher BMI (p < 0.01) and more ICU admissions (p = 0.02). The G8 score was significantly lower (p = 0.03) in the SGA-B/C group, suggesting coexisting functional decline. In terms of postoperative outcomes, the SGA-B/C group had a significantly longer postoperative hospital stay (p = 0.04). The 3-year OS rates for all stages were 100% in the SGA-A group and 49.7% in the SGA-B/C group (p = 0.03), while the 3-year OS rates for patients excluding Stage IV were 100% in the SGA-A group and 68.5% in the SGA-B/C group, not significantly different (p = 0.14). The 3-year RFS rate was 95.5% in the SGA-A group and 65.3% in the SGA-B/C group (p = 0.15). Conclusion The SGA is a promising nutritional index associated with short-term outcomes in older patients undergoing colorectal cancer surgery. The SGA can be assessed in a few minutes during an outpatient visit, making it useful for routine clinical use. 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. 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. 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. 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.

Wiley Acta Medica Okayama 1880-4276 41 4 2025 Prevalence, Characteristics, and Arrhythmogenic Substrate of Mitral Annular Disjunction Assessed by Cardiac Magnetic Resonance Imaging in Patients With Apparently Idiopathic Ventricular Arrhythmia e70172 EN Saori Asada Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihisa Toh Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Takuro Masuda Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Akira Ueoka Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Masakazu Miyamoto Department of Cardiology, Kagawa Prefectural Central Hospital Koji Nakagawa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Nobuhiro Nishii Kazufumi Nakamura Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Shinsuke Yuasa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Background: Mitral annular disjunction (MAD) is linked to an increased risk of sudden cardiac death, but its association with ventricular arrhythmias (VAs) in Japanese patients is unclear. Methods: We retrospectively analyzed 129 Japanese patients with VAs and no overt structural heart disease who underwent echocardiography and cardiac MRI. Results: MAD was diagnosed in 7.0%, and in 14% of patients with VAs originating from the mitral valve apparatus. MAD was significantly associated with multifocal VAs, late gadolinium enhancement in the papillary muscles, and greater mitral regurgitation. Conclusion: MAD may be an important arrhythmogenic substrate in apparently idiopathic VAs among Japanese patients. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 2363-9024 11 1 2025 Non-convulsive status epilepticus as a cause of delayed emergence after a thoracic surgery: a case report 30 EN Yusuke Iritani Department of Anesthesiology, Okayama Red Cross Hospital Makiko Tani Department of Anesthesiology and Resuscitology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Shinji Iga Department of Anesthesiology and Resuscitology, Okayama University Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Non-convulsive status epilepticus (NCSE) is an electrical discharge which occurs without prominent motor symptoms. NCSE is one of the causes of delayed emergence from anesthesia; however, as far as we know, previous reports of postoperative NCSE were related to patients after neurological surgery. Herein, we report a case of an elderly male who developed initial NCSE after thoracic surgery. The patient remained unresponsive and developed hemiplegia after lung resection, and then the symptoms fluctuated between better and worse. Metabolic disorders and stroke were ruled out, and NCSE was diagnosed by magnetic resonance imaging (MRI) and electroencephalography (EEG). NCSE occurred in a patient who had no predisposing factors or underwent non-neurological surgery. When anesthesiologists encounter delayed emergence, NCSE should be listed as a differential diagnosis and examined by MRI and EEG. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2692-4609 6 1 2025 A Case of Gastric Atypical Lipomatous Tumor/Well‐Differentiated Liposarcoma With Endoscopic Morphological Changes e70146 EN Rika Omote Department of Diagnostic Pathology, NHO Fukuyama Medical Center Shizuma Omote Department of Internal Medicine, Fukuyama Minami Hospital Hiroshi Sonobe Department of Diagnostic Pathology, NHO Fukuyama Medical Center Ryosuke Hamano Department of Surgery, NHO Fukuyama Medical Center Tatsuya Toyokawa Department of Gastroenterology, NHO Fukuyama Medical Center Shinya Otsuka Department of Surgery, NHO Fukuyama Medical Center Takehiro Tanaka Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Yanai Department of Pathology, Okayama University Hospital Masaru Inagaki Department of Surgery, NHO Fukuyama Medical Center Hidetaka Yamamoto Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atypical lipomatous tumor/well-differentiated liposarcoma is a locally aggressive mesenchymal neoplasm composed of adipocytes and stromal cells. Gastric cases are exceedingly rare, and their malignant potential remains unclear. We report a case of a woman in her 60s who was found to have multiple submucosal tumor-like lesions of the stomach. Over time, the tumors increased in size, requiring a laparoscopic partial gastrectomy. Histological examination revealed a tumor composed of both fatty tissue and fibrous stroma with nuclear atypia. Immunohistochemistry showed positivity for CDK4 and MDM2, and fluorescence in situ hybridization confirmed MDM2 amplification, leading to a diagnosis of atypical lipomatous tumor/well-differentiated liposarcoma. This case presented an unusual gastric manifestation, with multiple submucosal tumor-like lesions on endoscopy and exhibiting progressive morphological changes over several years. 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 ADAR1 as a prognostic marker for patients with colorectal cancer and synchronous liver metastasis and a predictor of chemotherapy efficacy 26752 EN Kaori Nitta Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshitaka Kondo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hibiki Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiaki Takahashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Moriwake Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Sho Takeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuki Matsumi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Kishimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masashi Kayano Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shunsuke Nakamura Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Michiue Neutron Therapy Research Center, Okayama University Hideki Yamamoto Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuhei Kondo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eiki Miyake Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 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 Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences RNA editing by adenosine deaminase acting on RNA (ADAR) enzymes plays a role in cancer progression. However, its clinical significance in metastatic colorectal cancer (CRC) remains unclear. This study aimed to evaluate whether ADAR1 expression predicts prognosis and treatment response in colorectal cancer (CRC) with synchronous liver metastasis. This study included 40 patients with stage IV CRC and synchronous liver metastases. ADAR1 expression in tumor tissues was evaluated using immunohistochemistry. Expression levels were quantified using the immunoreactive score, and associations with clinicopathological features, overall survival (OS), and chemotherapy response were examined. High ADAR1 expression was significantly associated with multiple liver metastases (P = 0.0206), lymph node metastasis (P = 0.0241), and reduced response to chemotherapy (P = 0.0224). Significantly shorter OS was observed in patients with high ADAR1 expression in the nucleus (P = 0.0458). ADAR1 expression was an independent prognostic factor comparable to the presence of extrahepatic metastases. Low ADAR1 expression was correlated with a higher likelihood of achieving a response to chemotherapy. ADAR1 expression can reflect tumor aggressiveness and chemotherapy resistance in patients with CRC and synchronous liver metastasis. ADAR1 has considerable potential as a dual-purpose biomarker for stratifying patients based on prognosis and optimizing treatment intensity. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2059-0105 10 1 2025 Oncolytic virus-mediated p53 activation boosts the antitumor immunity of a p53-transduced dendritic cell vaccine 158 EN Motohiko Yamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kanto Suemori Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naohiro Okada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Kajiwara 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 Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroaki Inoue Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoyuki Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Michiue Neutron Therapy Research Center, Okayama University Hospital Yasuo Urata Oncolys BioPharma, Inc Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Dendritic cells (DCs) transduced with replication-deficient, wild-type human p53-expressing adenovirus Ad-p53 (Ad-p53 DCs) induce p53-targeting cytotoxic T lymphocytes (CTLs). However, the antitumor efficacy of Ad-p53 DCs is diminished by weak p53 immunogenicity in tumor cells and poor immune responses. We developed a p53-armed oncolytic adenovirus, OBP-702, to induce tumor-specific p53 expression and antitumor immune response, suggesting a role for OBP-702 in enhancing the antitumor efficacy of Ad-p53 DCs. The combined effect of Ad-p53 DCs and OBP-702 was investigated using murine colon cancer (CC) tumor models. Ad-p53 DCs were obtained by stimulating bone marrow-derived cells with granulocyte-macrophage colony-stimulating factor, interleukin-4, and Ad-p53. Subcutaneous tumor models of CT26 (p53 wild-type) and MC38 (p53 mutant-type) murine CC cell lines were used to evaluate the therapeutic potential of combination therapy in the terms of tumor growth, abscopal effect, antitumor immune response, and presentation of p53 peptides in tumor cells. Combination therapy with Ad-p53 DCs and OBP-702 significantly suppressed the growth of p53-intact CT26 tumors at treated and untreated sites by inducing tumor-infiltration of CD8+ CTLs and CD11c+ DCs. OBP-702-infected tumor cells presented human p53 epitopes in the context of major histocompatibility complex molecules, which were recognized by CTLs induced by Ad-p53 DCs. Combination therapy significantly suppressed the growth of p53-mutant MC38 tumors by activating the antitumor immune response. Our results suggest that OBP-702-mediated presentation of p53 epitopes on tumor cells enhances the antitumor efficacy of Ad-p53 DCs against murine CC tumors by attracting p53-targeting CTLs. No potential conflict of interest relevant to this article was reported.

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

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

Wiley Acta Medica Okayama 1880-4276 41 3 2025 Acute effect of multipoint pacing and fused AV delay in patients receiving cardiac resynchronization therapy e70085 EN Masakazu Miyamoto Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nobuhiro Nishii Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomofumi Mizuno Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akira Ueoka Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takuro Masuda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Saori Asada Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Satoshi Kawada Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Koji Nakagawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: Cardiac resynchronization therapy (CRT) is an established treatment for patients with heart failure with dyssynchrony. However, one-third of patients do not respond positively to it. Recently, multipoint pacing (MPP), which involves pacing from two sites on the left ventricle, has been found to improve symptoms and hemodynamics compared to conventional CRT. An automatic fused atrioventricular (AV) delay that performs fused pacing for intrinsic conduction has also been introduced. However, the combined effect of MPP and fused AV delay on acute hemodynamics is unknown. Objective: To evaluate the acute hemodynamic effects of MPP and fused AV delay in patients undergoing CRT. Methods: A pressure wire was delivered to the left ventricle, and dp/dt was compared with single atrial stimulation pacing in 52 patients with various pacing configurations. Results: Delta dp/dt was greater in MPP than in conventional CRT (10.5 ± 1.0% vs. 8.2 ± 1.0%, p < 0.001) and in fused AV delay than in short AV delay (10.4 ± 0.8% vs. 8.3 ± 1.1, p < 0.001). Hemodynamic parameters significantly most improved with the combination of MPP and fused AV delay. Delta dp/dt was greater in LV pacing than in biventricular (BiV) pacing with MPP and fused AV delay; however, the delta QRS duration was shorter in LV pacing than in BiV pacing. Delta dp/dt and delta QRS duration were negatively correlated. The super-responder rate was 66%. Conclusion: Combining MPP and fused AV delay has an additional effect. Shortening the QRS duration can increase the dp/dt, but the estimated line differs between LV and BiV pacing. No potential conflict of interest relevant to this article was reported.

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

Japan Neurosurgical Society Acta Medica Okayama 2188-4226 12 2025 Safety of Adenosine-assisted Clipping Surgery for Unruptured Cerebral Aneurysms: Interim Results of a Single-center, Single-arm Study 115 119 EN Tomohito HISHIKAWA Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi MURAI Department of Neurosurgery, Kawasaki Medical School Masafumi HIRAMATSU Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun HARUMA Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki EBISUDANI 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 Kenji SUGIU Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuyoshi SHIMIZU Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji NAKAGAWA Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aya KIMURA-ONO Center for Innovative Clinical Medicine, Okayama University Hospital Katsuyuki HOTTA Center for Innovative Clinical Medicine, Okayama University Hospital Hiroshi MORIMATSU Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Isao DATE Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The aim of this single-center, single-arm study was to evaluate the safety of adenosine-assisted clipping surgery for unruptured cerebral aneurysms. Five patients underwent aneurysmal clipping during adenosine-induced hypotension at ≤60 mmHg. The mean age of patients was 63.4±8.5 years, and the mean aneurysm size was 5.3±1.1 mm. The prevalence of patients with modified Rankin Scale scores of zero 30 days after surgery was 100%. The degree of aneurysm obliteration was complete in 4 patients and residual dome in 1 patient. The mean total dosage of adenosine was 37.4±18.8 mg. The mean duration of systolic blood pressure at ≤60 mmHg was 64.2±28.3 secs. No patients exhibited paroxysmal atrial fibrillation within 24 hours after adenosine administration or elevation of high-sensitivity cardiac troponin T on postoperative day 1. There was no reduction in either motor-evoked or somatosensory-evoked potential amplitude during surgery. Adenosine-induced hypotension is a safe procedure in clipping surgery for unruptured cerebral aneurysms. 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.

Wiley Acta Medica Okayama 0014-5793 599 13 2025 Characterization of molecular mechanisms of CaMKKα/1 oligomerization 1914 1924 EN Shun Uenoyama Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Hayato Nitta Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Satomi Ohtsuka Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masaki Magari Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Futoshi Suizu Department of Medical Technology, Kagawa Prefectural University of Health Sciences Hiroshi Tokumitsu Calcium/calmodulin-dependent protein kinase kinase (CaMKK) is an activating kinase for calcium/calmodulin-dependent protein kinase type 1 (CaMKI), calcium/calmodulin-dependent protein kinase type IV (CaMKIV), RAC-alpha serine/threonine-protein kinase (PKB), and AMP-activated protein kinase (AMPK) that has been reported to form an active oligomer in cells. Glutathione S-transferase (GST) pulldown assay from the extracts of COS-7 cells expressing GST- and His6-CaMKKα/1 mutants showed that the C-terminal region containing the autoinhibitory and calmodulin (CaM)-binding sequence (residues 438–463) is required for CaMKKα/1 homo-oligomerization. This was confirmed by the fact that the GST-CaMKKα/1 C-terminal domain (residues 435–505) directly interacted with EGFP-CaMKKα/1 residues 435–505 as well as with wild-type CaMKKα/1. Notably, once oligomerized in cells, CaMKKα/1 is neither exchangeable between the oligomeric complexes nor dissociated by Ca2+/CaM binding. These results support stable oligomerization of CaMKK in the cells by intermolecular self-association of its C-terminal region containing a regulatory domain. No potential conflict of interest relevant to this article was reported.

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

Elmer Press, Inc. Acta Medica Okayama 1923-4155 16 5 2025 Nephronophthisis and Retinitis Pigmentosa (Senior-Loken Syndrome) After Living-Donor Kidney Transplantation: Twelve-Year Follow-Up in a Young Woman 164 173 EN Toshihiko Matsuo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yasuhiro Onishi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiroshi Morinaga Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Motoo Araki Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Senior-Loken syndrome is a hereditary ciliopathy with recessive trait that manifests as nephronophthisis and retinitis pigmentosa. This report described an 18-year-old woman who was referred to a University Hospital to set up a treatment plan for chronic renal failure of an unknown cause. She had experienced nocturnal polyurea from the age of 12 years and was found to have an elevated level of serum creatinine at 3 mg/dL at the age of 15 years. She underwent renal biopsy at a hometown regional hospital which showed global glomerulosclerosis in six of the 13 glomeruli examined, renal tubular dilation in irregular shape, and marked interstitial fibrosis with lymphocytic infiltration. At the age of 19 years, she received a living-donor kidney transplant from her 46-year-old father as a preemptive therapy. At surgery, biopsy of the father’s donor kidney showed two glomeruli with global sclerosis out of 24 glomeruli examined, in association with minimal interstitial fibrosis and lymphocytic infiltration. She began to have extended-release tacrolimus 4 mg daily and mycophenolate mofetil 1,000 mg daily. According to the standard protocol, she underwent biopsy of the transplanted donor kidney to reveal interstitial fibrosis and lymphocytic infiltration, in addition to no sign of rejection and no glomerular deposition of immunoglobulins and complements, both 4 weeks and 14 months after the kidney transplantation. At the age of 23 years, 4 years after the kidney transplantation, she was, for the first time, diagnosed retinitis pigmentosa, and hence, Senior-Loken syndrome. She was followed up in the stable condition with basal doses of tacrolimus 5 mg daily, mycophenolate mofetil 1,000 mg daily, and prednisolone 5 mg daily up until now in 12 years after the kidney transplantation. The interstitial fibrosis with lymphocytic infiltration in the donor kidney might be a milder presentation of the disease with recessive inheritance. No potential conflict of interest relevant to this article was reported.

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

Spandidos Publications Acta Medica Okayama 2049-9434 22 6 2025 Effects of aged garlic extract on experimental periodontitis in mice 97 EN Canyan Kuang Department of Pathophysiology‑Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Anna Hirai Division of Periodontics and Endodontics, Department of Dentistry, Okayama University Hospital Chiaki Kamei‑Νagata Division of Periodontics and Endodontics, Department of Dentistry, Okayama University Hospital Hiroshi Nango Central Research Institute, Wakunaga Pharmaceutical Co., Ltd. Masahiro Ohtani Central Research Institute, Wakunaga Pharmaceutical Co., Ltd. Kazuhiro Omori Department of Pathophysiology‑Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Takashiba Department of Pathophysiology‑Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aged garlic extract (AGE) has been reported to exert anti‑inflammatory effects. AGE has been recently found to reduce the inflammatory symptoms of periodontitis, a widespread chronic inflammatory disease caused by oral bacterial infection. However, the mechanisms underlying these effects remain unclear. In the present study, it was aimed to determine the effects of AGE on experimental periodontitis and the related inflammatory factors. AGE (2 g/kg/day) was orally administered to 15 mice during the experimental period, while a control group consisted of 15 mice that received pure water. A total of 3 days after initiation of administration, the left maxillary second molar was ligated with a 5‑0 silk thread for 7 days. Blood biochemical tests were performed to monitor the systemic effects of AGE. Alveolar bone loss was measured morphometrically using a stereomicroscope, and reverse transcription‑quantitative PCR was performed to assay mRNAs of proinflammatory cytokines in gingival tissues. A histological survey was also performed to identify osteoclasts in periodontitis lesions (five mice per group). The total protein and albumin levels showed no significant differences between the AGE and control groups. However, ligation‑induced bone resorption was lower in the AGE group than in the control group (P=0.01). Additionally, ligature increased the mRNA expression of inflammatory cytokines, whereas AGE administration tended to suppress them. Remarkably, tumor necrosis factor gene expression was significantly suppressed (P=0.04). The number of osteoclasts in periodontitis lesions was reduced in the AGE‑treated group. These results indicate that AGE prevents alveolar bone loss by suppressing the inflammatory responses related to osteoclast differentiation in the periodontal tissue. Further research is needed to elucidate the role of AGE in reducing inflammatory bone resorption. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0340-7004 74 7 2025 Osteosarcoma cell-derived CCL2 facilitates lung metastasis via accumulation of tumor-associated macrophages 193 EN Hiroya Kondo Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Fujiwara Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aki Yoshida Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Miho Kure Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Demiya Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Hata Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Uotani Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Joe Hasei Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Kunisada Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Yoshioka Department of Molecular and Cellular Medicine, Tokyo Medical University Toshifumi Ozaki Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Osteosarcoma (OS) is the most common malignant tumor of bone in children and adolescents. Although lung metastasis is a major obstacle to improving the prognosis of OS patients, the underlying mechanism of lung metastasis of OS is poorly understood. Tumor-associated macrophages (TAMs) with M2-like characteristics are reportedly associated with lung metastasis and poor prognosis in OS patients. In this study, we investigated the metastasis-associated tumor microenvironment (TME) in orthotopic OS tumor models with non-metastatic and metastatic OS cells. Non-metastatic and metastatic tumor cells derived from mouse OS (Dunn and LM8) and human OS (HOS and 143B) were used to analyze the TME associated with lung metastasis in orthotopic OS tumor models. OS cell-derived secretion factors were identified by cytokine array and enzyme-linked immunosorbent assay (ELISA). Orthotopic tumor models with metastatic LM8 and 143B cells were analyzed to evaluate the therapeutic potential of a neutralizing antibody in the development of primary and metastatic tumors. Metastatic OS cells developed metastatic tumors with infiltration of M2-like TAMs in the lungs. Cytokine array and ELISA demonstrated that metastatic mouse and human OS cells commonly secreted CCL2, which was partially encapsulated in extracellular vesicles. In vivo experiments demonstrated that while primary tumor growth was unaffected, administration of CCL2-neutralizing antibody led to a significant suppression of lung metastasis and infiltration of M2-like TAMs in the lung tissue. Our results suggest that CCL2 plays a crucial role in promoting the lung metastasis of OS cells via accumulation of M2-like TAMs. No potential conflict of interest relevant to this article was reported.

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

岡山大学理学部地球科学科 Acta Medica Okayama 1340-7414 31 1 2025 南西諸島の前弧域における付加体を含む堆積層のモデル化 1 15 EN Masanao KOMATSU Okayama Gakuin University Sohei URAKAMI Formerly Department of Earth Sciences, Okayama University Taro OKAMOTO Department of Earth and Planetary Sciences, School of Science, Institute of Science Tokyo Hiroshi TAKENAKA Department of Earth Sciences, Okayama University 10.18926/ESR/68676 　We combine the recent seismic reflection profiles to construct a new seismic velocity model of the sedimentary layer incorporating the accretionary prism along the Ryukyu trench. In constructing the new model, we refer to the zoning (ZONE1 to ZONE4) identified by Okamura et al. (2017, Tectonophys.). The construction process consists of the following steps: First, we digitize either unconformities or VP=4 to 5 km/s lines as the seismic basement, whichever is more clearly identifiable. Second, the digitized thickness data of the sedimentary layer from the reflection profiles are geometrically modeled and interpolated to make the three-dimensional structure model. Finally, we supplement the external region of the constructed 3-D sedimentary model using the J-SHIS model provided by the NIED to complete the velocity structure model in the entire Ryukyu arc. The main features of our model are as follows: In ZONE1, off Ishigaki-jima island, the thick sedimentary layer extends about 50 km wide from the Ryukyu trench. In ZONE2, off Miyako-jima island, the thinner layer compared to the other zones is found near the trench, with a thin sedimentary terrace covering the area behind it. In ZONE3, off Okinawa-jima island, the sedimentary layer deepens as it approaches the trench. In ZONE4, off Tokara islands, the deepest layer among all zones is identified. We then conduct 3-D finite-difference simulations of seismic wave propagation using the new and the previous models to confirm the improvement of the new model. In the simulations, the effects of the accretionary prism along the Ryukyu trench on the seismic wave propagation are clearly identified. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1477-9560 23 1 2025 Anticoagulant effects of edoxaban in cancer and noncancer patients with venous thromboembolism 36 EN Masashi Yoshida Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Matsuo Department of General Internal Medicine 3, Kawasaki Medical School Takanori Naito Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Kuroda Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital Koji Tokioka Department of Cardiovascular Medicine, Okayama City Hospital Kunihiko Hatanaka Department of Cardiovascular Medicine, Japanese Red Cross Society Himeji Hospital Ryohei Fujimoto Department of Cardiovascular Medicine, Tsuyama Chuo Hospital Hidenaru Yamaoka Department of Cardiovascular Medicine, Okayama Rosai Hospital Yutaka Kajikawa Department of Cardiovascular Medicine, NHO Fukuyama Medical Center Kazuki Suruga Department of Cardiovascular Medicine, Okayama Medical Center Hiroki Sugiyama Department of Cardiovascular Medicine, Okayama Saiseikai General Hospital Tsuyoshi Miyaji Hosogi Hospital Yoshimasa Morimoto Department of Cardiovascular Medicine, Fukuyama City Hospital Nobuhiro Okamura Okamura Isshindow Hospital Toshihiro Sarashina Kuroda Clinic Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ito Department of General Internal Medicine 3, Kawasaki Medical School Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Background Edoxaban, a direct oral anticoagulant (DOAC), is a first-line treatment for venous thromboembolism (VTE) and the suppression of VTE recurrence. In patients with cancer, however, recurrent VTE after DOAC treatment may be more common than in noncancer patients. To evaluate our hypothesis that the anticoagulation effect of edoxaban is lower in VTE patients with cancer than in noncancer patients. Methods This study was a prospective, multicenter, observational study including patients treated with edoxaban for VTE in Japan. The primary outcome was the difference in the prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimer level at 5 h after initial edoxaban administration between the cancer and noncancer groups. An additional outcome was the longitudinal change in PT and APTT from 5 h to overnight after edoxaban administration. The incidence of adverse events was further investigated. Results PT and APTT at 5 h after initial edoxaban administration were not significantly different between the cancer (n = 84) and noncancer groups (n = 138) (e.g., log-transformed APTT 3.55 vs. 3.55, p = 0.45). However, D-dimer in the cancer groups was significantly greater than that in the noncancer groups (log-transformed 1.83 vs. 1.79, p = 0.009). PT and APTT significantly decreased from 5 h to overnight after edoxaban, but a similar pattern was observed in each group. All adverse events after edoxaban administration were also similar between patients with cancer and noncancer. Conclusion PT and APTT after edoxaban administration were similar between VTE patients with cancer and noncancer groups, suggesting that edoxaban has anticoagulation effects on cancer-associated VTE similar to those of noncancer patients. Trial registration UMIN000041973; Registration Date: 2020.10.5. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 79 2 2025 Effectiveness of Postoperative Irradiation in Patients with cN0 Early Breast Cancer Treated with Sentinel Lymph Node Surgery 101 107 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 Original Article 10.18926/AMO/68648 To evaluate the effectiveness of postoperative irradiation (POI) for patients with cN0 early breast cancer, we retrospectively analyzed the cases of 650 consecutive breast cancer patients who underwent sentinel lymph node (SLN)-guided surgery (2005-2022) at our hospital. In this cohort, 53% (278/521) of the patients who underwent breast conservative surgery (BCS) and 96% (124/129) of those treated with mastectomy did not receive POI. The patients who underwent BCS were treated with POI using opposing tangential field irradiation. A false negative (FN) SLN was retrospectively defined as a negative metastasis in SLN plus positive recurrence in the axillary lymph nodes. Recurrence was detected in 83 patients. A logistic regression analysis revealed that the nuclear grade (odds ratio [OR] 1.69), POI (OR 0.41), and postoperative hormone therapy (OR 0.40) were each significantly related to recurrence. The 26.1% (12/46) FN rate of the non-POI patients decreased to 5.8% (1/17) compared to those treated with POI. The rate of axillary recurrence was significantly lower in the POI group (0.4%) versus the non-POI group (2.7%) (p=0.0355). The rate of locoregional recurrence was also significantly lower in the POI group (2.0%) versus the non-POI group (13.4%) (p<0.0001). No significant difference was observed in the rate of distant recurrence between the POI (4.0%) and non-POI (3.3%) (p=0.831) groups. These results indicated that the postoperative opposing tangential field irradiation of conserved breast tissue inhibited recurrence in the axillary lymph nodes. 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.

Elsevier Acta Medica Okayama 1083-351X 301 4 2025 Roles of basic amino acid residues in substrate binding and transport of the light-driven anion pump Synechocystis halorhodopsin (SyHR) 108334 EN Masaki Nakama Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoyasu Noji Department of Applied Chemistry, The University of Tokyo Keiichi Kojima Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Susumu Yoshizawa Atmosphere and Ocean Research Institute, The University of Tokyo Hiroshi Ishikita Department of Applied Chemistry, The University of Tokyo Yuki Sudo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Microbial rhodopsins are photoreceptive seventransmembrane a-helical proteins, many of which function as ion transporters, primarily for small monovalent ions such as Na+, K+, Cl-, Br-, and I-. Synechocystis halorhodopsin (SyHR), identified from the cyanobacterium Synechocystis sp. PCC 7509, uniquely transports the polyatomic divalent SO42- inward, in addition to monovalent anions (Cl- and Br-). In this study, we conducted alanine-scanning mutagenesis on twelve basic amino acid residues to investigate the anion transport mechanism of SyHR. We quantitatively evaluated the Cl-and SO42- transport activities of the WT SyHR and its mutants. The results showed a strong correlation between the Cl-and SO42- transport activities among them (R = 0.94), suggesting a shared pathway for both anions. Notably, the R71A mutation selectively abolished SO42- transport activity while maintaining Cl- transport, whereas the H167A mutation significantly impaired both Cl-and SO42- transport. Furthermore, spectroscopic analysis revealed that the R71A mutant lost its ability to bind SO42- due to the absence of a positive charge, while the H167A mutant failed to accumulate the O intermediate during the photoreaction cycle (photocycle) due to reduced hydrophilicity. Additionally, computational analysis revealed the SO42- binding modes and clarified the roles of residues involved in its binding around the retinal chromophore. Based on these findings and previous structural information, we propose that the positive charge and hydrophilicity of Arg71 and His167 are crucial for the formation of the characteristic initial and transient anion-binding site of SyHR, enabling its unique ability to bind and transport both Cl-and SO42-. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1380-3743 45 3 2025 Rapid development of naked malting barley germplasm through targeted mutagenesis 32 EN Hiroshi Hisano Institute of Plant Science and Resources, Okayama University Hiroaki Sakai Research Center for Advanced Analysis, National Agriculture and Food Research Organization Mika Hamaoka Institute of Plant Science and Resources, Okayama University Hiromi Munemori Institute of Plant Science and Resources, Okayama University Fumitaka Abe Institute of Crop Science, National Agriculture and Food Research Organization Brigid Meints Department Crop and Soil Science, Oregon State University Kazuhiro Sato Institute of Plant Science and Resources, Okayama University Patrick M. Hayes Department Crop and Soil Science, Oregon State University Covered barley (Hordeum vulgare) has historically been preferred for malting, as the husk in this plant protects the embryo during harvest and acts as a filter during brewing. Naked barley, which is typically used as food, has the potential to be used in brewing due to recent technical advances, but the grains contain higher levels of β-glucan and polyphenols, which are undesirable in brewing. Introducing the naked trait into brewing cultivars through crossing is time-consuming due to the need to eliminate these undesirable traits. In this study, we rapidly developed naked barley that is potentially suitable for malting by introducing targeted mutations into Nudum (NUD) using CRISPR/Cas9-mediated targeted mutagenesis. The doubled haploid line ‘DH120366’, which was used as the parental line, was derived from a cross between two covered malting barley cultivars. We generated CRISPR/Cas9-mediated targeted mutagenized barley harboring mutations in NUD via Agrobacterium tumefaciens-mediated transformation and confirmed the presence of mosaic mutations in one individual from among 16 T0 transformants. We sowed T1 grains exhibiting the naked trait and sequenced the NUD gene in these T1 seedlings, identifying two types of mutations. Shotgun high-throughput whole-genome sequencing confirmed the absence of the transgene in at least one nud mutant line following k-mer-based analysis. Cultivation in a closed growth chamber revealed no significant differences in agronomic traits between the nud mutants and the wild type. This study demonstrates the feasibility of rapidly developing naked barley with potential use for malting and brewing by targeting only NUD via targeted mutagenesis. 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.

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

Wiley Acta Medica Okayama 0965-7576 2025 Wake Not a Sleeping Lion: Free Trade Agreements and Decision Rights in Multinationals EN Hiroshi Mukunoki Faculty of Economics, Gakushuin University Hirofumi Okoshi Faculty of Economics, Okayama University Free trade agreements with rules of origin affect the location of input production for vertically integrated multinational enterprises. The relocation induced by a free trade agreement changes the allocation of decision rights within multinational enterprises and the purpose of transfer pricing from avoiding high taxes to strengthening their product market competitiveness. This study shows that a free trade agreement with rules of origin may hurt both a multinational enterprise and a local firm, despite tariff elimination, when the relocation occurs and the decision rights change from centralization to decentralization. Moreover, such a free trade agreement can hurt consumers. Nevertheless, rules of origin increase the feasibility of free trade agreements due to larger tax revenues. No potential conflict of interest relevant to this article was reported.

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

Informa UK Limited Acta Medica Okayama 1323-5818 45 1 2024 A new species of Ovassiminea Thiele, 1927 (Gastropoda: Truncatelloidea: Assimineidae) from the Yaeyama Islands, Okinawa, southern Japan ― the northernmost record among recent species of the genus 58 73 EN Hiroshi Fukuda Conservation of Aquatic Biodiversity, Faculty of Agriculture, Okayama University Hirofumi Kubo Okinawa Prefectural Institute of Health and Environment Ovassiminea hayasei n. sp. is described from mangrove swamps in Iriomote and Ishigaki Islands, of the Yaeyama Islands at the southwestern part of the Ryūkyū Archipelago, Okinawa, Japan. This is the northernmost record among recent species of the genus Ovassiminea Thiele, 1927, which is distributed in the tropical and subtropical regions of the Western Pacific. The new species is known to be restricted to extremely narrow ranges and is evaluated as vulnerable in red lists by the governments of Japan and Okinawa Prefecture. A list of all available (five recent and five fossil) species names of Ovassiminea hitherto described, with synonymies, is also given as an Appendix. No potential conflict of interest relevant to this article was reported.

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

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

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 4 2025 上西川町の窪田次郎、そして勤のこと 274 280 EN Hiroshi YAMASHITA 資料紹介 (Materials and data) 10.18926/67962 No potential conflict of interest relevant to this article was reported.

岡山大学文学部 Acta Medica Okayama 0285-4864 77 2024 祭礼行事・民俗芸能の維持・存続に関する研究の展開状況─その数量的把握の試み─ 15 26 EN Hiroshi TAKANO 10.18926/okadai-bun-kiyou/67915 No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 187 2024 意味づけするとは何か 145 151 EN Hiroshi MIYAZAKI Faculty of Education, Okayama University Takuya SOBUKAWA Global Education Center, Waseda University 10.18926/bgeou/67901 　人間はコミュニケーションの動物であると言われる。しかしその対象についての解釈（意味）が異なればコミュニケーションは成立しない。本論では意味づけするとはどういうことなのかについて考える。 No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2470-1343 9 50 2024 Conformational Flexibility of D1-Glu189: A Crucial Determinant in Substrate Water Selection, Positioning, and Stabilization within the Oxygen-Evolving Complex of Photosystem II 50041 50048 EN Hiroshi Isobe Research Institute for Interdisciplinary Science, Okayama University Takayoshi Suzuki Research Institute for Interdisciplinary Science, Okayama University Michihiro Suga Research Institute for Interdisciplinary Science, Okayama University Jian-Ren Shen Research Institute for Interdisciplinary Science, Okayama University Kizashi Yamaguchi Center for Quantum Information and Quantum Biology, Osaka University Photosynthetic water oxidation is a vital process responsible for producing dioxygen and supplying the energy necessary to sustain life on Earth. This fundamental reaction is catalyzed by the oxygen-evolving complex (OEC) of photosystem II, which houses the Mn4CaO5 cluster as its catalytic core. In this study, we specifically focus on the D1-Glu189 amino acid residue, which serves as a direct ligand to the Mn4CaO5 cluster. Our primary goal is to explore, using density functional theory (DFT), how the conformational flexibility of the D1-Glu189 side chain influences crucial catalytic processes, particularly the selection, positioning, and stabilization of a substrate water molecule within the OEC. Our investigation is based on a hypothesis put forth by Li et al. (Nature, 2024, 626, 670), which suggests that during the transition from the S2 to S3 state, a specific water molecule temporarily coordinating with the Ca ion, referred to as O6*, may exist as a hydroxide ion (OH-). Our results demonstrate a key mechanism by which the detachment of the D1-Glu189 carboxylate group from its coordination with the Ca ion allows the creation of a specialized microenvironment within the OEC that enables the selective attraction of O6* in its deprotonated form (OH-) and stabilizes it at the catalytic metal (MnD) site. Our findings indicate that D1-Glu189 is not only a structural ligand for the Ca ion but may also play an active and dynamic role in the catalytic process, positioning O6* optimally for its subsequent participation in the oxidation sequence during the water-splitting cycle. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Carboxyhemoglobin and Methemoglobin Levels and Hemolysis in Children Undergoing Cardiac Surgery With Cardiopulmonary Bypass EN Tsubasa YOSHIDA 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 Near-infrared Photoimmunotherapy Targeting Cancer-Associated Fibroblasts in Patient-Derived Xenografts Using a Humanized Anti-Fibroblast Activation Protein Antibody EN Teruki KOBAYASHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

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

Japan Prosthodontic Society Acta Medica Okayama 1883-1958 68 1 2023 Tooth morphology fusion technique is more accurate than conventional technique in transferring morphology of provisional to definitive screw-retained, implant-supported crown: A preliminary intervention study 139 146 EN Takuya Mino Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yoko Kurosaki Department of Oral Rehabilitation and Implantology, Okayama University Hospital Kana Tokumoto Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Koji Izumi SHIKEN Corporation Hiroshi Mitsumune SHIKEN Corporation Kenji Maekawa Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Ueda Dental Technician Laboratory, Okayama University Hospital Tomohito Nakano Dental Technician Laboratory, Okayama University Hospital Junichi Sejima Dental Technician Laboratory, Okayama University Hospital Aya Kimura-Ono Department of Oral Rehabilitation and Implantology, Okayama University Hospital Takuo Kuboki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Purpose: To compare the accuracy of the tooth morphology fusion (TMF) digital technique and customized impression transfer coping (conventional) technique when transferring the morphology of a provisional crown to a definitive screw-retained implant-supported crown. Methods: Six cases of partial edentulism (one anterior and five posterior) treated with oral implant placement in our clinic for the loss of three or fewer teeth in the maxilla or mandible between April 2017 and September 2018 were included. After implant placement and re-entry surgery, provisional restorations were made and adjusted to obtain the ideal morphology. Two definitive restorations were constructed by transferring the complete morphology of the provisional restorations, including the subgingival contour, using the TMF digital and conventional techniques. Three sets of surface morphological data were obtained using a desktop scanner. The three-dimensional total discrepancy volume (TDV) between the provisional restoration (reference) and the two definitive restorations was digitally measured by overlapping the surface data of the stone cast using the Boolean operation. Each TDV ratio (%) was calculated by dividing the TDV by the volume of provisional restoration. The median TDV ratios for TMF and conventional techniques were compared using the Wilcoxon signed-rank test. Results: The median TDV ratio between provisional and definitive restorations constructed using the TMF digital technique (8.05%) was significantly lower than that obtained using the conventional technique (13.56%, P < 0.05). Conclusions: In this preliminary intervention study, the TMF digital technique was more accurate than the conventional technique for the transfer of morphology from provisional to definitive prosthesis. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 19 10 2024 The protective effect of carbamazepine on acute lung injury induced by hemorrhagic shock and resuscitation in rats e0309622 EN Yaqiang Li Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroko Shimizu Department of Anesthesiology and Resuscitology, Okayama University Medical School Ryu Nakamura Department of Anesthesiology and Resuscitology, Okayama University Medical School Yifu Lu Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Risa Sakamoto Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Emiko Omori Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Takahashi Okayama Saidaiji Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hemorrhagic shock and resuscitation (HSR) enhances the risk of acute lung injury (ALI). This study investigated the protective effect of carbamazepine (CBZ) on HSR-induced ALI in rats. Male Sprague-Dawley rats were allocated into five distinct groups through randomization: control (SHAM), saline + HSR (HSR), CBZ + HSR (CBZ/HSR), dimethyl sulfoxide (DMSO) + HSR (DMSO/HSR), and CBZ + chloroquine (CQ) + HSR (CBZ/CQ/HSR). Subsequently, HSR models were established. To detect tissue damage, we measured lung histological changes, lung injury scores, and wet/dry weight ratios. We measured neutrophil counts as well as assessed the expression of inflammatory factors using RT-PCR to determine the inflammatory response. We detected autophagy-related proteins LC3II/LC3I, P62, Beclin-1, and Atg12-Atg5 using western blotting. Pretreatment with CBZ improved histopathological changes in the lungs and reduced lung injury scores. The CBZ pretreatment group exhibited significantly reduced lung wet/dry weight ratio, neutrophil aggregation and number, and inflammation factor (TNF-alpha and iNOS) expression. CBZ changed the expression levels of autophagy-related proteins (LC3II/LC3I, beclin-1, Atg12-Atg5, and P62), suggesting autophagy activation. However, after injecting CQ, an autophagy inhibitor, the beneficial effects of CBZ were reversed. Taken together, CBZ pretreatment improved HSR-induced ALI by suppressing inflammation, at least in part, through activating autophagy. Thus, our study offers a novel perspective for treating HSR-induced ALI. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1432-0851 74 1 2024 Dendritic cell maturation is induced by p53-armed oncolytic adenovirus via tumor-derived exosomes enhancing systemic antitumor immunity 12 EN Tomoko Ohtani Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kento Kumon Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiaki Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoma Sugimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Dendritic cells (DCs) are crucial in cancer immunity, because they activate cytotoxic T cells by presenting tumor antigens. Recently, oncolytic virus therapy has been recognized as a systemic immune stimulator. We previously developed a telomerase-specific oncolytic adenovirus (OBP-301) and a p53-armed OBP-301 (OBP-702), demonstrating that these viruses strongly activate systemic antitumor immunity. However, their effects on DCs remained unclear. In the present study, the aim was to elucidate the mechanisms of DC activation by OBP-702, focusing particularly on tumor-derived exosomes. Exosomes (Exo53, Exo301, or Exo702) were isolated from conditioned media of human or murine pancreatic cancer cell lines (Panc-1, MiaPaCa-2, and PAN02) after treatment with Ad-p53, OBP-301, or OBP-702. Exo702 derived from Panc-1 and MiaPaCa-2 cells significantly upregulated CD86, CD80, CD83 (markers of DC maturation), and IFN-γ in DCs in vitro. Similarly, Exo702 derived from PAN02 cells upregulated CD86 and IFN-γ in bone marrow-derived DCs in a bilateral PAN02 subcutaneous tumor model. This DC maturation was inhibited by GW4869, an inhibitor of exosome release, and anti-CD63, an antibody targeting the exosome marker. Intratumoral injection of OBP-702 into PAN02 subcutaneous tumors significantly increased the presence of mature DCs and CD8-positive T cells in draining lymph nodes, leading to long-lasting antitumor effects through the durable activation of systemic antitumor immunity. In conclusion, tumor-derived exosomes play a significant role in DC maturation following OBP-702 treatment and are critical for the systemic activation of antitumor immunity, leading to the abscopal effect. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-4409 13 16 2024 Direct Binding of Synaptopodin 2-Like Protein to Alpha-Actinin Contributes to Actin Bundle Formation in Cardiomyocytes 1373 EN Hiroshi Yamada Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirona Osaka Graduate School of Science, Nagoya University Nanami Tatsumi Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miu Araki Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Abe Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiko Kaihara Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Takahashi Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eizo Takashima Division of Malaria Research, Proteo-Science Center, Ehime University Takayuki Uchihashi Graduate School of Science, Nagoya University Keiji Naruse Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohji Takei Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Synaptopodin 2-like protein (SYNPO2L) is localized in the sarcomere of cardiomyocytes and is involved in heart morphogenesis. However, the molecular function of SYNPO2L in the heart is not fully understood. We investigated the interaction of SYNPO2L with sarcomeric alpha-actinin and actin filaments in cultured mouse cardiomyocytes. Immunofluorescence studies showed that SYNPO2L colocalized with alpha-actinin and actin filaments at the Z-discs of the sarcomere. Recombinant SYNPO2La or SYNPO2Lb caused a bundling of the actin filaments in the absence of alpha-actinin and enhanced the alpha-actinin-dependent formation of actin bundles. In addition, high-speed atomic force microscopy revealed that SYNPO2La directly bound to alpha-actinin via its globular ends. The interaction between alpha-actinin and SYNPO2La fixed the movements of the two proteins on the actin filaments. These results strongly suggest that SYNPO2L cooperates with alpha-actinin during actin bundle formation to facilitate sarcomere formation and maintenance. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 78 4 2024 Pneumocephalus with Inverted Papilloma in the Frontoethmoidal Sinus: Case Report and Literature Review 337 343 EN Seiichiro Makihara Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiro Otani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Uraguchi Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sawako Ono Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aiko Shimizu Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryosuke Ikemachi Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Okazaki Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Ota Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Matsumoto Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shotaro Miyamoto Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital Munechika Tsumura Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital Seiya Hayashi Department of Neurosurgery, Kagawa Rosai Hospital Michiari Umakoshi Department of Neurosurgery, Kagawa Rosai Hospital Koji Hirashita Department of Neurosurgery, Kagawa Rosai Hospital Mizuo Ando Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/67550 Here, we describe the unique case of a pneumocephalus originating from an inverted papilloma (IP) in the frontoethmoidal sinus. A 71-year-old man with diabetes presented with headaches and altered consciousness. Imaging revealed the pneumocephalus together with bone destruction in the left frontal sinus. He underwent simultaneous endoscopic endonasal and transcranial surgery using an ORBEYE exoscope. Pathological diagnosis of the tumor confirmed IP. Post-surgery, the pneumocephalus was significantly resolved and the squamous cell carcinoma antigen level, which had been elevated, decreased. This case underscores the importance of a multidisciplinary approach and innovative surgical methods in treating complex sinonasal pathologies. No potential conflict of interest relevant to this article was reported.

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

MDPI Acta Medica Okayama 2077-0383 13 15 2024 Impact of Serum Indoxyl Sulfate on One-Year Adverse Events in Chronic Kidney Disease Patients with Heart Failure 4384 EN Keiichiro Iwasaki Department of Cardiovascular Medicine, Okayama University Institute of Academic and Research, Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Institute of Academic and Research, Medicine, Dentistry and Pharmaceutical Sciences Chikara Urabe Department of Cardiovascular Medicine, Okayama University Institute of Academic and Research, Medicine, Dentistry and Pharmaceutical Sciences Satoru Sakuragi Department of Cardiovascular Medicine, Iwakuni Clinical Center Yusuke Kawai Department of Cardiovascular Medicine, Okayama City Hospital Soichiro Fuke Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital Masayuki Doi Department of Cardiology, Kagawa Prefectural Central Hospital Atsushi Takaishi Department of Cardiology, Mitoyo General Hospital Takefumi Oka Department of Cardiology, Tsuyama Chuo Hospital Naoto Tokunaga Department of Cardiology, Ibara City Hospital Hiroshi Ito Department of General Internal Medicine 3, Kawasaki Medical School Background/Objectives: Indoxyl sulfate, a uremic toxin, is associated with mortality and cardiovascular events in patients with chronic kidney disease (CKD). This study aimed to evaluate the prognostic implications of serum indoxyl sulfate levels in patients with heart failure and CKD. Methods and Results: This was a prospective multicenter observational study. Overall, 300 patients with chronic heart failure with a previous history of hospitalization and an estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73 m2 or less (CKD stage G3b to G5) without dialysis were analyzed. The primary outcome assessed in a time-to-event analysis from the measurement of indoxyl sulfate was a composite of all-cause death, hospitalization for heart failure, nonfatal myocardial infarction, and nonfatal stroke. Clinical events were followed-up to one year after indoxyl sulfate measurement. The median patient age was 75 years, and 57% of the patients were men. We divided the cohort into low and high indoxyl sulfate categories according to a median value of 9.63 mg/mL. The primary outcome occurred in 27 of 150 patients (18.0%) in the low indoxyl sulfate group and 27 of 150 patients (18.0%) in the high indoxyl sulfate group (hazard ratio, 1.00; 95% confidence interval, 0.58 to 1.70, p = 0.99). In the post hoc exploratory analyses, the results were consistent across age, sex, body mass index, left ventricular ejection fraction, eGFR, and N-terminal pro b-type natriuretic peptide. Conclusions: Among heart failure patients with CKD stages G3b to 5G, serum indoxyl sulfate concentrations were not significantly associated with the subsequent occurrence of cardiovascular events. No potential conflict of interest relevant to this article was reported.

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

Royal Society of Chemistry Acta Medica Okayama 2041-6520 15 32 2024 Boosting charge separation in organic photovoltaics: unveiling dipole moment variations in excited non-fullerene acceptor layers 12686 12694 EN Akira Yamakata Graduate School of Natural Science and Technology, Okayama University Kosaku Kato Graduate School of Natural Science and Technology, Okayama University Takumi Urakami Department of Molecular Engineering, Graduate School of Engineering, Kyoto University Sota Tsujimura Department of Chemistry, Graduate School of Science, Kobe University Kasumi Murayama Department of Chemistry, Graduate School of Science, Kobe University Masahiro Higashi Department of Complex Systems Science, Graduate School of Informatics, Nagoya University Hirofumi Sato Department of Molecular Engineering, Graduate School of Engineering, Kyoto University Yasuhiro Kobori Department of Chemistry, Graduate School of Science, Kobe University Tomokazu Umeyama Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo Hiroshi Imahori Department of Molecular Engineering, Graduate School of Engineering, Kyoto University The power conversion efficiency (PCE) of organic photovoltaics (OPVs) has reached more than 19% due to the rapid development of non-fullerene acceptors (NFAs). To compete with the PCEs (26%) of commercialized silicon-based inorganic photovoltaics, the drawback of OPVs should be minimized. This drawback is the intrinsic large loss of open-circuit voltage; however, a general approach to this issue remains elusive. Here, we report a discovery regarding highly efficient NFAs, specifically ITIC. We found that charge-transfer (CT) and charge dissociation (CD) can occur even in a neat ITIC film without the donor layer. This is surprising, as these processes were previously believed to take place exclusively at donor/acceptor heterojunctions. Femtosecond time-resolved visible to mid-infrared measurements revealed that in the neat ITIC layers, the intermolecular CT immediately proceeds after photoirradiation (<0.1 ps) to form weakly-bound excitons with a binding energy of 0.3 eV, which are further dissociated into free electrons and holes with a time-constant of 56 ps. Theoretical calculations indicate that stacking faults in ITIC (i.e., V-type molecular stacking) induce instantaneous intermolecular CT and CD in the neat ITIC layer. In contrast, J-type stacking does not support such CT and CD. This previously unknown pathway is triggered by the larger dipole moment change on the excited state generated at the lower symmetric V-type molecular stacking of ITIC. This is in sharp contrast with the need of sufficient energy offset for CT and CD at the donor-acceptor heterojunction, leading to the significant voltage loss in conventional OPVs. These results demonstrate that the rational molecular design of NFAs can increase the local dipole moment change on the excited state within the NFA layer. This finding paves the way for a groundbreaking route toward the commercialization of OPVs. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1547-5271 21 10 2024 Risk stratification for the occurrence of ventricular fibrillation in patients with early repolarization syndrome 1787 1794 EN Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Saori Asada Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Akira Ueoka Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Tomofumi Mizuno Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Takuro Masuda Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Masakazu Miyamoto Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Satoshi Kawada Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Koji Nakagawa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Nobuhiro Nishii Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Background Several signs of malignant early repolarizations have been proposed in patients with early repolarization syndrome (ERS). However, reports have challenged the efficacy of these signs in predicting future ventricular fibrillation (VF) in patients with ERS. Objective This study aimed to assess the predictive value of various electrocardiogram (ECG) markers for future VF events in patients with ERS. Methods We retrospectively evaluated the clinical characteristics of 44 patients with ERS to identify risk factors for VF during follow-up. Results After the initial event, 16 patients experienced VF (VF group), whereas 28 did not (non-VF group). The VF group had a longer QRS interval, more fragmented QRS (fQRS), and a higher T/R voltage ratio than the non-VF group. Wide J waves were more prevalent in the VF group; however, other J-wave markers did not differ between the groups. Positive late potentials recorded on signal-averaged ECGs were more frequent in the VF group. Whereas none of the patients showed spontaneous Brugada syndrome on ECG, the VF group frequently exhibited pilsicainide-induced ST-segment elevation. These ECG markers were significantly associated with the occurrence of VF during follow-up. Patients with multiple ECG factors, including QRS abnormalities (wide QRS or fQRS), wide J waves, and a high T/R ratio, had a worse prognosis than patients without multiple factors, effectively stratifying patient risk. Conclusion The occurrence of VF in patients with ERS may be associated with conduction abnormalities such as QRS widening, fQRS, high T/R ratio, positive late potentials, and pilsicainide test results. Therefore, ECG factors could be useful in identifying high-risk patients. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 0250-7005 44 6 2024 Senescent Fibroblasts Potentiate Peritoneal Metastasis of Diffuse-type Gastric Cancer Cells via IL-8–mediated Crosstalk 2497 2509 EN YUNCHENG LI Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences HIROSHI TAZAWA Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences YASUO NAGAI Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences SHUTO FUJITA Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TOMOHIRO OKURA Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences RYOHEI SHOJI Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences MOTOHIKO YAMADA Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences SATORU KIKUCHI Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences SHINJI KURODA Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TOSHIAKI OHARA Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences KAZUHIRO NOMA Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences MASAHIKO NISHIZAKI Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences SHUNSUKE KAGAWA Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TOSHIYOSHI FUJIWARA Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Aim: Diffuse-type gastric cancer (DGC) often forms peritoneal metastases, leading to poor prognosis. However, the underlying mechanism of DGC-mediated peritoneal metastasis is poorly understood. DGC is characterized by desmoplastic stroma, in which heterogeneous cancer-associated fibroblasts (CAFs), including myofibroblastic CAFs (myCAFs) and senescent CAFs (sCAFs), play a crucial role during tumor progression. This study investigated the CAF subtypes induced by GC cells and the role of sCAFs in peritoneal metastasis of DGC cells. Materials and Methods: Conditioned medium of human DGC cells (KATOIII, NUGC-4) and human intestinal-type GC (IGC) cells (MKN-7, N87) was used to induce CAFs. CAF subtypes were evaluated by analyzing the expression of α–smooth muscle actin (α-SMA), senescence-associated β-galactosidase (SA-β-gal), and p16 in human normal fibroblasts (GF, FEF-3). A cytokine array was used to explore the underlying mechanism of GC-induced CAF subtype development. The role of sCAFs in peritoneal metastasis of DGC cells was analyzed using a peritoneally metastatic DGC tumor model. The relationships between GC subtypes and CAF-related markers were evaluated using publicly available datasets. Results: IGC cells significantly induced α-SMA+ myCAFs by secreting transforming growth factor–β, whereas DGC cells induced SA-β-gal+/p16+ sCAFs by secreting interleukin (IL)-8. sCAFs further secreted IL-8 to promote DGC cell migration. In vivo experiments demonstrated that co-inoculation of sCAFs significantly enhanced peritoneal metastasis of NUGC-4 cells, which was attenuated by administration of the IL-8 receptor antagonist navarixin. p16 and IL-8 expression was significantly associated with poor prognosis of DGC patients. Conclusion: sCAFs promote peritoneal metastasis of DGC via IL-8–mediated crosstalk. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 2296-858X 11 2024 Late-onset renal variant Fabry disease with R112H mutation and mild increase in plasma globotriaosylsphingosine: a case report 1383309 EN Keiko Tanaka Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Hitoshi Sugiyama Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Hiroshi Morinaga Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Akifumi Onishi Department of Nephrology, Fukuyama City Hospital Katsuyuki Tanabe Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Haruhito A. Uchida Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Hiroki Maruyama Department of Clinical Nephroscience, Niigata University Graduate School of Medical and Dental Sciences Jun Wada Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Fabry disease (FD) is an X-linked disorder resulting in a deficiency of alpha-galactosidase A (GLA) activity. The R112H mutation of GLA is relatively common in Japanese FD patients, characterized by a late-onset phenotype, almost normal to mild lyso-Gb3 elevation, and mild clinical symptoms, despite low GLA activity. This is due to the structural features of the R112H GLA protein. We herein report the case of a 42-year-old male patient with late-onset FD with a R112H mutation. The patient exhibited only renal involvement with no other organ damage and was successfully treated with galactosidase beta and subsequent migalastat for approximately 10 years. Especially, migalastat was clinically effective in normalizing plasma lyso-Gb3 levels and inhibiting the progression of renal damage associated with FD. Therefore, the use of migalastat in the FD patients with R112H mutation is highly recommended based on this case report. 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.

Springer Science and Business Media LLC Acta Medica Okayama 2662-4729 47 3 2024 Evaluation of output factors of different radiotherapy planning systems using Exradin W2 plastic scintillator detector 1177 1189 EN Yasuharu Ando Hiroshima City Hospital Masahiro Okada Hiroshima City North Medical Center Asa Citizens Hospital Natsuko Matsumoto Hiroshima City North Medical Center Asa Citizens Hospital Kawasaki Ikuhiro Hiroshima City North Medical Center Asa Citizens Hospital Soichiro Ishihara Hiroshima City Hospital Hiroshi Kiriu Hiroshima City Hospital Yoshinori Tanabe Department of Radiological Technology, Graduate School of Health Sciences, Okayama University This study aims to evaluate the output factors (OPF) of different radiation therapy planning systems (TPSs) using a plastic scintillator detector (PSD). The validation results for determining a practical field size for clinical use were verified. The implemented validation system was an Exradin W2 PSD. The focus was to validate the OPFs of the small irradiation fields of two modeled radiation TPSs using RayStation version 10.0.1 and Monaco version 5.51.10. The linear accelerator used for irradiation was a TrueBeam with three energies: 4, 6, and 10 MV. RayStation calculations showed that when the irradiation field size was reduced from 10 × 10 to 0.5 × 0.5 cm2, the results were within 2.0% of the measured values for all energies. Similarly, the values calculated using Monaco were within approximately 2.0% of the measured values for irradiation field sizes between 10 × 10 and 1.5 × 1.5 cm2 for all beam energies of interest. Thus, PSDs are effective validation tools for OPF calculations in TPS. A TPS modeled with the same source data has different minimum irradiation field sizes that can be calculated. These findings could aid in verification of equipment accuracy for treatment planning requiring highly accurate dose calculations and for third-party evaluation of OPF calculations for TPS. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2047-0525 13 1 2024 Sensitivity and specificity of the question “do you have any concerns regarding your mouth related to undergoing surgery?” for predicting perioperative oral health problems in patients with primary esophageal and lung cancer: a retrospective observational study 36 EN Aiko Yoshitomi Division of Hospital Dentistry, Okayama University Hospital Yoshihiko Soga Division of Hospital Dentistry, Okayama University Hospital Reiko Yamanaka-Kohno Division of Hospital Dentistry, Okayama University Hospital Hiroshi Morimatsu Perioperative Management Center, Okayama University Hospital Background Perioperative oral management contributes to the prevention of dental/systemic complications. However, a professional dental checkup before surgery is generally not performed and relies on the patient’s answer to a simple question by medical professionals other than dentists: “Do you have any concerns regarding your mouth related to undergoing surgery?” Here, we evaluated the sensitivity and specificity of this question for predicting perioperative oral health problems in patients with primary esophageal and primary lung cancer. Methods We performed an oral cavity check in all patients before scheduled surgery for primary esophageal and lung cancer. A total of 183 patients were enrolled (M, 112; F, 71; 24–88 years, median, 69 years), consisting of 61 with primary esophageal cancer (M, 46; F, 15; 24–85 years, median, 69 years) and 122 with primary lung cancer (M, 66; F; 56; 33–88 years, median, 69 years). All subjects provided a response to this question, and an oral cavity check was performed by dentists. The sensitivity and specificity of this question for detecting oral health problems were evaluated retrospectively. Results Overall sensitivity and specificity for detecting oral health problems were 0.263 and 0.898, respectively. There were no significant differences by sex or disease (primary esophageal or lung cancer). Conclusion This simple question has low sensitivity but high specificity for detecting oral health problems. Although challenging to detect surgical patients with oral health problems by simply asking questions, the results indicated that patients with oral complaints are more likely to have problems during surgery. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0961-8368 32 10 2023 Molecular mechanism of the common and opposing cosolvent effects of fluorinated alcohol and urea on a coiled coil protein e4763 EN Noa Nakata Department of Chemistry, Faculty of Science, Okayama University Ryuichi Okamoto Graduate School of Information Science, University of Hyogo Tomonari Sumi Department of Chemistry, Faculty of Science, Okayama University Kenichiro Koga Department of Chemistry, Faculty of Science, Okayama University Takeshi Morita Department of Chemistry, Graduate School of Science, Chiba University Hiroshi Imamura Department of Bio-Science, Nagahama Institute of Bio-Science and Technology Alcohols and urea are widely used as effective protein denaturants. Among monohydric alcohols, 2,2,2-trifluoroethanol (TFE) has large cosolvent effects as a helix stabilizer in proteins. In contrast, urea efficiently denatures ordered native structures, including helices, into coils. These opposing cosolvent effects of TFE and urea are well known, even though both preferentially bind to proteins; however, the underlying molecular mechanism remains controversial. Cosolvent-dependent relative stability between native and denatured states is rigorously related to the difference in preferential binding parameters (PBPs) between these states. In this study, GCN4-p1 with two-stranded coiled coil helices was employed as a model protein, and molecular dynamics simulations for the helix dimer and isolated coil were conducted in aqueous solutions with 2 M TFE and urea. As 2 M cosolvent aqueous solutions did not exhibit clustering of cosolvent molecules, we were able to directly investigate the molecular origin of the excess PBP without considering the enhancement effect of PBPs arising from the concentration fluctuations. The calculated excess PBPs of TFE for the helices and those of urea for the coils were consistent with experimentally observed stabilization of helix by TFE and that of coil by urea. The former was caused by electrostatic interactions between TFE and side chains of the helices, while the latter was attributed to both electrostatic and dispersion interactions between urea and the main chains. Unexpectedly, reverse-micelle-like orientations of TFE molecules strengthened the electrostatic interactions between TFE and the side chains, resulting in strengthening of TFE solvation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 28 7 2023 Trends and issues in clinical research on satisfaction and quality of life after mastectomy and breast reconstruction: a 5-year scoping review 847 859 EN Miho Saiga Department of Plastic Surgery, Okayama University Hospital Ryoko Nakagiri Department of Plastic Surgery, Okayama University Hospital Yuko Mukai Department of Plastic Surgery, Okayama Rosai Hospital Hiroshi Matsumoto Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Breast reconstruction (BR) aims to improve the satisfaction and quality of life (QOL) of breast cancer survivors. Clinical studies using patient-reported outcomes (PROs) can therefore provide relevant information to the patients and support decision-making. This scoping review was conducted to analyze recent trends in world regions, methods used, and factors investigated. The literature search was conducted in August 2022. Databases of PubMed, MEDLINE, and CINAHL were searched for relevant English-language studies published from 2017 to 2022. Studies involving women with breast cancer who underwent BR after mastectomy and investigated PROs after BR using BR-specific scales were included. Data on the country, publication year, study design, PRO measures (PROMs) used, time points of surveys, and research themes were collected. In total, 147 articles met the inclusion criteria. BREAST-Q was the most widely used, contributing to the increase in the number and diversification of studies in this area. Such research has been conducted mainly in North America and Europe and is still developing in Asia and other regions. The research themes involved a wide range of clinical and patient factors in addition to surgery, which could be influenced by research methods, time since surgery, and even cultural differences. Recent BR-specific PROMs have led to a worldwide development of research on factors that affect satisfaction and QOL after BR. PRO after BR may be influenced by local cultural and social features, and it would be necessary to accumulate data in each region to draw clinically useful conclusion. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0340-7004 72 11 2023 PD-L1-expressing cancer-associated fibroblasts induce tumor immunosuppression and contribute to poor clinical outcome in esophageal cancer 3787 3802 EN Kento Kawasaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Kato Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Ohara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasushige Takeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hijiri Matsumoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seitaro Nishimura Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyoshi Kunitomo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaaki Akai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Teruki Kobayashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriyuki Nishiwaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hajime Kashima Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Shirakawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The programmed cell death 1 protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays a crucial role in tumor immunosuppression, while the cancer-associated fibroblasts (CAFs) have various tumor-promoting functions. To determine the advantage of immunotherapy, the relationship between the cancer cells and the CAFs was evaluated in terms of the PD-1/PD-L1 axis. Overall, 140 cases of esophageal cancer underwent an immunohistochemical analysis of the PD-L1 expression and its association with the expression of the α smooth muscle actin, fibroblast activation protein, CD8, and forkhead box P3 (FoxP3) positive cells. The relationship between the cancer cells and the CAFs was evaluated in vitro, and the effect of the anti-PD-L1 antibody was evaluated using a syngeneic mouse model. A survival analysis showed that the PD-L1+ CAF group had worse survival than the PD-L1- group. In vitro and in vivo, direct interaction between the cancer cells and the CAFs showed a mutually upregulated PD-L1 expression. In vivo, the anti-PD-L1 antibody increased the number of dead CAFs and cancer cells, resulting in increased CD8+ T cells and decreased FoxP3+ regulatory T cells. We demonstrated that the PD-L1-expressing CAFs lead to poor outcomes in patients with esophageal cancer. The cancer cells and the CAFs mutually enhanced the PD-L1 expression and induced tumor immunosuppression. Therefore, the PD-L1-expressing CAFs may be good targets for cancer therapy, inhibiting tumor progression and improving host tumor immunity. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 19 2 2024 Fluorescence-guided assessment of bone and soft-tissue sarcomas for predicting the efficacy of telomerase-specific oncolytic adenovirus e0298292 EN Koji Uotani Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Center for Innovative Clinical Medicine, Okayama University Hospital Joe Hasei 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 Aki Yoshida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuaki Yamakawa 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 Tadashi Komatsubara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroya Kondo Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Morita Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Kiyono Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Suguru Yokoo Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Hata 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 Ken Takeda Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Bone and soft-tissue sarcomas are rare malignancies with histological diversity and tumor heterogeneity, leading to the lack of a common molecular target. Telomerase is a key enzyme for keeping the telomere length and human telomerase reverse transcriptase (hTERT) expression is often activated in most human cancers, including bone and soft-tissue sarcomas. For targeting of telomerase-positive tumor cells, we developed OBP-301, a telomerase-specific replication-competent oncolytic adenovirus, in which the hTERT promoter regulates adenoviral E1 gene for tumor-specific viral replication. In this study, we present the diagnostic potential of green fluorescent protein (GFP)-expressing oncolytic adenovirus OBP-401 for assessing virotherapy sensitivity using bone and soft-tissue sarcomas. OBP-401-mediated GFP expression was significantly associated with the therapeutic efficacy of OBP-401 in human bone and soft-tissue sarcomas. In the tumor specimens from 68 patients, malignant and intermediate tumors demonstrated significantly higher expression levels of coxsackie and adenovirus receptor (CAR) and hTERT than benign tumors. OBP-401-mediated GFP expression was significantly increased in malignant and intermediate tumors with high expression levels of CAR and hTERT between 24 and 48 h after infection. Our results suggest that the OBP-401-based GFP expression system is a useful tool for predicting the therapeutic efficacy of oncolytic virotherapy on bone and soft-tissue sarcomas. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 0040-5752 136 4 2023 FLOURY ENDOSPERM 6 mutations enhance the sugary phenotype caused by the loss of ISOAMYLASE1 in barley 94 EN Ryo Matsushima Institute of Plant Science and Resources, Okayama University Hiroshi Hisano Institute of Plant Science and Resources, Okayama University Ivan Galis Institute of Plant Science and Resources, Okayama University Satoko Miura Department of Biological Production, Akita Prefectural University Naoko Crofts Department of Biological Production, Akita Prefectural University Yuto Takenaka College of Life Sciences, Ritsumeikan University Naoko F. Oitome Department of Biological Production, Akita Prefectural University Takeshi Ishimizu College of Life Sciences, Ritsumeikan University Naoko Fujita Department of Biological Production, Akita Prefectural University Kazuhiro Sato Institute of Plant Science and Resources, Okayama University Starch is a biologically and commercially important glucose polymer synthesized by plants as semicrystalline starch granules (SGs). Because SG morphology affects starch properties, mutants with altered SG morphology may be useful in breeding crops with desirable starch properties, including potentially novel properties. In this study, we employed a simple screen for mutants with altered SG morphology in barley (Hordeum vulgare). We isolated mutants that formed compound SGs together with the normal simple SGs in the endosperm and found that they were allelic mutants of the starch biosynthesis genes ISOAMYLASE1 (HvISA1) and FLOURY ENDOSPERM 6 (HvFLO6), encoding starch debranching enzyme and CARBOHYDRATE-BINDING MODULE 48-containing protein, respectively. We generated the hvflo6 hvisa1 double mutant and showed that it had significantly reduced starch biosynthesis and developed shrunken grains. In contrast to starch, soluble α-glucan, phytoglycogen, and sugars accumulated to higher levels in the double mutant than in the single mutants. In addition, the double mutants showed defects in SG morphology in the endosperm and in the pollen. This novel genetic interaction suggests that hvflo6 acts as an enhancer of the sugary phenotype caused by hvisa1 mutation. 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 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 Impact of Travel Distance on Surgical Outcomes of Patients Surgically Treated for Non-Small Cell Lung Cancer: A Single-Center Study in Ehime, Japan 143 149 EN Hisayuki Shigematsu Department of Thoracic Surgery, NHO Shikoku Cancer Center Natsumi Yamashita Clinical Research Center, NHO Shikoku Cancer Center Hiroshi Suehisa Department of Thoracic Surgery, NHO Shikoku Cancer Center Tsuyoshi Ueno Department of Thoracic Surgery, NHO Shikoku Cancer Center Tsuyoshi Ryuko Department of Thoracic Surgery, NHO Shikoku Cancer Center Takahito Sugihara Department of Thoracic Surgery, NHO Shikoku Cancer Center Shohei Nakashima Department of Thoracic Surgery, NHO Shikoku Cancer Center Yoshifumi Sano Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine Motohiro Yamashita Department of Thoracic Surgery, NHO Shikoku Cancer Center Original Article 10.18926/AMO/66923 Travel burden is a poor prognostic factor for many cancers worldwide because it hinders optimal diagnosis and treatment planning. Currently, the impact of travel burden on survival after surgery for non-small cell lung cancer (NSCLC) in Japan is largely unexplored. We examined the impact of travel distance on the postoperative outcomes of patients with NSCLC in Ehime Prefecture, Japan. The data of 1212 patients who underwent surgical resection for NSCLC were retrospectively reviewed. Patients were divided into quartiles based on the travel distance from their home to the hospital (≤ 13 km, 13-40 km, 40-57 km, and > 57 km) in Ehime Prefecture. We found no significant differences among the quartiles in baseline clinicopathological characteristics, including sex, smoking status, histology, surgical procedure, clinical stage, and pathological stage. Overall survival (OS) and relapse-free survival (RFS) also were not significantly different among the travel distance quartiles. We conclude that travel distance did not impact OS or RFS among patients with NSCLC who underwent surgical resection at our institution. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1880-4276 40 3 2024 Artificial intelligence to detect noise events in remote monitoring data 560 577 EN Nobuhiro Nishii Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kensuke Baba Cyber-Physical Engineering Informatics Research Core, Okayama University Ken'Ichi Morooka Division of Industrial Innovation Sciences, Graduate School of Natural Science and Technology, Okayama University Haruto Shirae Division of Industrial Innovation Sciences, Graduate School of Natural Science and Technology, Okayama University Tomofumi Mizuno Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takuro Masuda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akira Ueoka Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Saori Asada Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masakazu Miyamoto Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Satoshi Kawada Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Koji Nakagawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: Remote monitoring (RM) of cardiac implantable electrical devices (CIEDs) can detect various events early. However, the diagnostic ability of CIEDs has not been sufficient, especially for lead failure. The first notification of lead failure was almost noise events, which were detected as arrhythmia by the CIED. A human must analyze the intracardiac electrogram to accurately detect lead failure. However, the number of arrhythmic events is too large for human analysis. Artificial intelligence (AI) seems to be helpful in the early and accurate detection of lead failure before human analysis. Objective: To test whether a neural network can be trained to precisely identify noise events in the intracardiac electrogram of RM data. Methods: We analyzed 21 918 RM data consisting of 12 925 and 1884 Medtronic and Boston Scientific data, respectively. Among these, 153 and 52 Medtronic and Boston Scientific data, respectively, were diagnosed as noise events by human analysis. In Medtronic, 306 events, including 153 noise events and randomly selected 153 out of 12 692 nonnoise events, were analyzed in a five-fold cross-validation with a convolutional neural network. The Boston Scientific data were analyzed similarly. Results: The precision rate, recall rate, F1 score, accuracy rate, and the area under the curve were 85.8 ± 4.0%, 91.6 ± 6.7%, 88.4 ± 2.0%, 88.0 ± 2.0%, and 0.958 ± 0.021 in Medtronic and 88.4 ± 12.8%, 81.0 ± 9.3%, 84.1 ± 8.3%, 84.2 ± 8.3% and 0.928 ± 0.041 in Boston Scientific. Five-fold cross-validation with a weighted loss function could increase the recall rate. Conclusions: AI can accurately detect noise events. AI analysis may be helpful for detecting lead failure events early and accurately. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 14 1 2024 Development of a novel AAK1 inhibitor via Kinobeads-based screening 6723 EN Akari Yoshida Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Satomi Ohtsuka Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Fumiya Matsumoto Department of Science Education, Graduate School of Education, Okayama University Tomoyuki Miyagawa Department of Science Education, Graduate School of Education, Okayama University Rei Okino Department of Science Education, Graduate School of Education, Okayama University Yumeya Ikeda Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Natsume Tada Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Akira Gotoh Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masaki Magari Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Naoya Hatano Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ryo Morishita CellFree Sciences Co. Ltd Ayano Satoh Organelle Systems Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yukinari Sunatsuki Graduate School of Natural Science and Technology, Okayama University Ulf J. Nilsson Department of Chemistry, Lund University Teruhiko Ishikawa Department of Science Education, Graduate School of Education, Okayama University Hiroshi Tokumitsu Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University A chemical proteomics approach using Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) inhibitor-immobilized sepharose (TIM-063-Kinobeads) identified main targets such as CaMKK alpha/1 and beta/2, and potential off-target kinases, including AP2-associated protein kinase 1 (AAK1), as TIM-063 interactants. Because TIM-063 interacted with the AAK1 catalytic domain and inhibited its enzymatic activity moderately (IC50 = 8.51 mu M), we attempted to identify potential AAK1 inhibitors from TIM-063-derivatives and found a novel AAK1 inhibitor, TIM-098a (11-amino-2-hydroxy-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one) which is more potent (IC50 = 0.24 mu M) than TIM-063 without any inhibitory activity against CaMKK isoforms and a relative AAK1-selectivity among the Numb-associated kinases family. TIM-098a could inhibit AAK1 activity in transfected cultured cells (IC50 = 0.87 mu M), indicating cell-membrane permeability of the compound. Overexpression of AAK1 in HeLa cells significantly reduced the number of early endosomes, which was blocked by treatment with 10 mu M TIM-098a. These results indicate TIM-063-Kinobeads-based chemical proteomics is efficient for identifying off-target kinases and re-evaluating the kinase inhibitor (TIM-063), leading to the successful development of a novel inhibitory compound (TIM-098a) for AAK1, which could be a molecular probe for AAK1. TIM-098a may be a promising lead compound for a more potent, selective and therapeutically useful AAK1 inhibitor. No potential conflict of interest relevant to this article was reported.

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

岡山大学理学部地球科学科 Acta Medica Okayama 1340-7414 30 1 2024 岡山大学津島キャンパスおける微動探査 13 20 EN Nobuyuki YAMADA Faculty of Science and Technology, Kochi University Hiroshi TAKENAKA Department of Earth Sciences, Okayama University 10.18926/ESR/66845 　In this report, microtremor array observations were conducted in the Tsushima Campus of Okayama University, and the subsurface velocity structure was estimated from the analysis of the records. The results indicate that a five-layer S-wave velocity structure from the surface to the seismic basement equivalent layer with thicknesses of 8, 24, 80 and 180 m and velocities of 150, 450, 1100, 1700 and 3200 m/s, respectively, is reasonable. This model explains to some extent the observed phase velocity and H/V spectral ratios. It is also consistent with the surface borehole results. Furthermore, the areal characteristics of the H/V spectral ratios were also presented, allowing us to estimate the trend of the ground structure in shallow areas. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 2324-7096 12 2024 Pericardial Effusion in Association With Periodontitis: Case Report and Review of 8 Patients in Literature EN Toshihiko Matsuo Okayama University Chie Nakago Matsuo Okayama University Nobuhiko Matsuo Okayama University Ayano Mori Nagashima Hospital Masaaki Murakami Okayama Heart Clinic Hiroshi Ito Okayama University Periodontal diseases are well-known background for infective endocarditis. Here, we show that pericardial effusion or pericarditis might have origin also in periodontal diseases. An 86-year-old man with well-controlled hypertension and diabetes mellitus developed asymptomatic increase in pericardial effusion. Two weeks previously, he took oral new quinolone antibiotics for a week because he had painful periodontitis along a dental bridge in the mandibular teeth on the right side and presented cheek swelling. The sputum was positive for Streptococcus species. He was healthy and had a small volume of pericardial effusion for the previous 5 years after drug-eluting coronary stents were inserted at the left anterior descending branch 10 years previously. The differential diagnoses listed for pericardial effusion were infection including tuberculosis, autoimmune diseases, and metastatic malignancy. Thoracic to pelvic computed tomographic scan demonstrated no mass lesions, except for pericardial effusion and a small volume of pleural effusion on the left side. Fluorodeoxyglucose positron emission tomography disclosed many spotty uptakes in the pericardial effusion. The patient denied pericardiocentesis, based on his evaluation of the risk of the procedure. He was thus discharged in several days and followed at outpatient clinic. He underwent dental treatment and pericardial effusion resolved completely in a month. He was healthy in 6 years until the last follow-up at the age of 92 years. We also reviewed 8 patients with pericarditis in association with periodontal diseases in the literature to reveal that periodontal diseases would be the background for developing infective pericarditis and also mediastinitis on some occasions. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1043-3074 46 5 2024 Combined simultaneous endoscopic endonasal and transcranial surgery using high‐definition three‐dimensional exoscope for malignant tumors of the anterior skull base 1074 1082 EN Seiichiro Makihara Department of Otolaryngology – Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiro Otani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Uraguchi Department of Otolaryngology – Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aiko Shimizu Department of Otolaryngology – Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aya Murai Department of Otolaryngology – Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaya Higaki Department of Otolaryngology – Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoki Akisada Department of Otolaryngology – Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Fujimoto Department of Otolaryngology – Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuma Makino Department of Otolaryngology – Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Joji Ishida Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Fujii 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 Tomoyuki Ota Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Hiroshi Matsumoto Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Mizuo Ando Department of Otolaryngology – Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Advanced surgical interventions are required to treat malignancies in the anterior skull base (ASB). This study investigates the utility of endoscopic endonasal and transcranial surgery (EETS) using a high-definition three-dimensional exoscope as an alternative to traditional microscopy. Methods: Six patients with carcinomas of varying histopathologies underwent surgery employing the EETS maneuver, which synchronized three distinct surgical modalities: harvesting of the anterolateral thigh flap, initiation of the transnasal technique, and initiation of the transcranial procedure. Results: The innovative strategy enabled successful tumor resection and skull base reconstruction without postoperative local neoplastic recurrence, cerebrospinal fluid leakage, or neurological deficits. Conclusion: The integration of the exoscope and EETS is a novel therapeutic approach for ASB malignancies. This strategy demonstrates the potential of the exoscope in augmenting surgical visualization, enhancing ergonomics, and achieving seamless alignment of multiple surgical interventions. This technique represents a progressive shift in the management of these complex oncological challenges. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0007-0920 130 7 2024 Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus 1187 1195 EN Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Kadowaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaki Sakamoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Hamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoma Sugimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiaki Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Ohtani Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kento Kumon Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahito Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Pancreatic cancer is an aggressive, immunologically “cold” tumor. Oncolytic virotherapy is a promising treatment to overcome this problem. We developed a telomerase-specific oncolytic adenovirus armed with p53 gene (OBP-702). Methods: We investigated the efficacy of OBP-702 for pancreatic cancer, focusing on its long-term effects via long-lived memory CD8 + T cells including tissue-resident memory T cells (TRMs) and effector memory T cells (TEMs) differentiated from effector memory precursor cells (TEMps). Results: First, in vitro, OBP-702 significantly induced adenosine triphosphate (ATP), which is important for memory T cell establishment. Next, in vivo, OBP-702 local treatment to murine pancreatic PAN02 tumors increased TEMps via ATP induction from tumors and IL-15Rα induction from macrophages, leading to TRM and TEM induction. Activation of these memory T cells by OBP-702 was also maintained in combination with gemcitabine+nab-paclitaxel (GN) in a PAN02 bilateral tumor model, and GN + OBP-702 showed significant anti-tumor effects and increased TRMs in OBP-702-uninjected tumors. Finally, in a neoadjuvant model, in which PAN02 cells were re-inoculated after resection of treated-PAN02 tumors, GN + OBP-702 provided long-term anti-tumor effects even after tumor resection. Conclusion: OBP-702 can be a long-term immunostimulant with sustained anti-tumor effects on immunologically cold pancreatic cancer. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1466-8033 26 7 2024 The effect of solvent molecules on crystallisation of heterotrinuclear MII–TbIII–MII complexes with tripodal nonadentate ligands 1004 1014 EN Kazuma Takahara Graduate School of Natural Science and Technology, Okayama University Yuki Horino Graduate School of Natural Science and Technology, Okayama University Koki Wada Graduate School of Natural Science and Technology, Okayama University Hiromu Sakata Graduate School of Natural Science and Technology, Okayama University Daichi Tomita Faculty of Science, Okayama University Yukinari Sunatsuki Advanced Science Research Center, Okayama University Hiroshi Isobe Research Institute for Interdisciplinary Science, Okayama University Masaaki Kojima Graduate School of Natural Science and Technology, Okayama University Takayoshi Suzuki Graduate School of Natural Science and Technology, Okayama University The crystal structures and crystallisation behaviours of MII–TbIII–MII heterotrinuclear complexes, [(L)MTbM(L)]NO3 (M = Mn and Zn; L3－ stands for a conjugated base of H3L = 1,1,1-tris[(3-methoxysalicylideneamino)methyl]ethane), obtained from various organic solvents (MeOH, EtOH, CH2Cl2 and CHCl3) were investigated. The trinuclear complex cation has two asymmetric centres (Δ or Λ) at two MII sites as a result of the twisted tripodal arms of L3－. Single-crystal X-ray diffraction analysis revealed that all the analysed Zn–Tb–Zn complexes had homochiral structures (Δ,Δ- or Λ,Λ-enantiomers) in each single crystal; however, the type of crystallisation behaviour showed clear differences depending on the type of solvent molecule. Specifically, crystallisation from MeOH or CH2Cl2 resulted in the exclusive formation of the Λ-conglomerates with the Λ,Λ-enantiomers―a phenomenon we recently termed ‘absolute spontaneous resolution’. The analogous Mn–Tb–Mn complex crystallised from MeOH also resulted in the same phenomenon as that of Zn–Tb–Zn. In contrast, the meso-type (Δ,Λ) achiral isomer of the Mn–Tb–Mn complex was deposited for the first time in a series of MII–LnIII–MII trinuclear complexes from a CH2Cl2 or EtOH solution. Density functional theory calculations were performed to compare the thermodynamic stability of homochiral (Λ,Λ) and meso-type (Δ,Λ) complex cations of [(L)MnTbMn(L)]+ in MeOH and EtOH. Results were consistent with the molecular structures observed in the crystallographic analysis of the compounds deposited from these solvents. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 18 11 2023 p53-armed oncolytic adenovirus induces autophagy and apoptosis in KRAS and BRAF-mutant colorectal cancer cells e0294491 EN Shuta Tamura Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoto Hori Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuncheng Li 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 Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Colorectal cancer (CRC) cells harboring KRAS or BRAF mutations show a more-malignant phenotype than cells with wild-type KRAS and BRAF. KRAS/BRAF-wild-type CRCs are sensitive to epidermal growth factor receptor (EGFR)-targeting agents, whereas KRAS/BRAF-mutant CRCs are resistant due to constitutive activation of the EGFR-downstream KRAS/BRAF signaling pathway. Novel therapeutic strategies to treat KRAS/BRAF mutant CRC cells are thus needed. We recently demonstrated that the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 exhibit therapeutic potential against KRAS-mutant human pancreatic cancer cells. In this study, we evaluated the therapeutic potential of OBP-301 and OBP-702 against human CRC cells with differing KRAS/BRAF status. Human CRC cells with wild-type KRAS/BRAF (SW48, Colo320DM, CACO-2), mutant KRAS (DLD-1, SW620, HCT116), and mutant BRAF (RKO, HT29, COLO205) were used in this study. The antitumor effect of OBP-301 and OBP-702 against CRC cells was analyzed using the XTT assay. Virus-mediated modulation of apoptosis, autophagy, and the EGFR-MEK-ERK and AKT-mTOR signaling pathways was analyzed by Western blotting. Wild-type and KRAS-mutant CRC cells were sensitive to OBP-301 and OBP-702, whereas BRAF-mutant CRC cells were sensitive to OBP-702 but resistant to OBP-301. Western blot analysis demonstrated that OBP-301 induced autophagy and that OBP-702 induced autophagy and apoptosis in human CRC cells. In BRAF-mutant CRC cells, OBP-301 and OBP-702 suppressed the expression of EGFR, MEK, ERK, and AKT proteins, whereas mTOR expression was suppressed only by OBP-702. Our results suggest that p53-armed oncolytic virotherapy is a viable therapeutic option for treating KRAS/BRAF-mutant CRC cells via induction of autophagy and apoptosis. No potential conflict of interest relevant to this article was reported.

Oxford University Press Acta Medica Okayama 2474-9842 8 1 2024 Epidural versus patient-controlled intravenous analgesia on pain relief and recovery after laparoscopic gastrectomy for gastric cancer: randomized clinical trial zrad161 EN Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Matsusaki Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hajime Kashima Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuo Takata Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ema Mitsui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Epidural analgesia (EDA) is a main modality for postoperative pain relief in major open abdominal surgery within the Enhanced Recovery After Surgery protocol. However, it remains unclear whether EDA is an imperative modality in laparoscopic gastrectomy (LG). This study examined non-inferiority of patient-controlled intravenous analgesia (PCIA) to EDA in terms of postoperative pain and recovery in patients who underwent LG. Methods: In this open-label, non-inferiority, parallel, individually randomized clinical trial, patients who underwent elective LG for gastric cancer were randomized 1:1 to receive either EDA or PCIA after surgery. The primary endpoint was pain score using the Numerical Rating Scale at rest 24 h after surgery, analysed both according to the intention-to-treat (ITT) principle and per protocol. The non-inferiority margin for pain score was set at 1. Secondary outcomes were postoperative parameters related to recovery and adverse events related to analgesia. Results: Between 3 July 2017 and 29 September 2020, 132 patients were randomized to receive either EDA (n = 66) or PCIA (n = 66). After exclusions, 64 patients were included in the EDA group and 65 patients in the PCIA group for the ITT analysis. Pain score at rest 24 h after surgery was 1.94 (s.d. 2.07) in the EDA group and 2.63 (s.d. 1.76) in the PCIA group (P = 0.043). PCIA was not non-inferior to EDA for the primary endpoint (difference 0.69, one side 95% c.i. 1.25, P = 0.184) in ITT analysis. Postoperative parameters related to recovery were similar between groups. More EDA patients (21 (32.8%) versus 1 (1.5%), P < 0.001) developed postoperative hypotension as an adverse event. Conclusions: PCIA was not non-inferior to EDA in terms of early-phase pain relief after LG. Registration number: UMIN000027643 (https://www.umin.ac.jp/ctr/index-j.htm). Conclusions: PCIA was not non-inferior to EDA in terms of early-phase pain relief after LG.Registration number: UMIN000027643 (https://www.umin.ac.jp/ctr/index-j.htm). No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 13 1 2023 Bundling of collagen fibrils influences osteocyte network formation during bone modeling 22028 EN Mana Hashimoto Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haruka Takahashi Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kaori Tabata-Okubo Department of Orthodontics, Okayama University Hospital Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Kazuaki Tokunaga Nikon Corporation Haruka Matsumori Nikon Corporation Yoshihito Ishihara Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaru Kaku Division of Bio‑prosthodontics, Faculty of Dentistry and Graduate School of Medical and Dental Sciences, Niigata University Tadahiro Iimura Department of Pharmacology, Faculty and Graduate School of Dental Medicine, Hokkaido University Toru Hara Research Center for Structural Materials, National Institute for Materials Science Hiroshi Kamioka Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Osteocytes form a cellular network by gap junctions between their cell processes. This network is important since intercellular communication via the network is essential for bone metabolism. However, the factors that influence the formation of this osteocyte network remain unknown. As the early stage of osteocyte network formation occurs on the bone surface, we observed a newly formed trabecular bone surface by orthogonal focused ion beam-scanning electron microscopy. The embedding late osteoblast processes tended to avoid bundled collagen fibrils and elongate into sparse collagen fibrils. Then, we examined whether the inhibition of bundling of collagen fibrils using a potent lysyl oxidase inhibitor, beta-aminopropionitrile (BAPN) changed the cellular network of the chick calvaria. The osteocyte shape of the control group was spindle-shape, while that of the BAPN group was sphere-shaped. In addition, the osteocyte processes of the control group were elongated vertically to the long axis of the cell body, whereas the osteocyte processes of the BAPN group were elongated radially. Therefore, it was suggested that the bundling of collagen fibrils influences normal osteocyte network formation during bone modeling. No potential conflict of interest relevant to this article was reported.

eLife Sciences Publications Acta Medica Okayama 2050-084X 12 2023 Characterization of tryptophan oxidation affecting D1 degradation by FtsH in the photosystem II quality control of chloroplasts RP88822 EN Yusuke Kato Institute of Plant Science and Resources (IPSR), Okayama University Hiroshi Kuroda Research Institute for Interdisciplinary Science, Okayama University Shin-Ichiro Ozawa Institute of Plant Science and Resources (IPSR), Okayama University Keisuke Saito Research Center for Advanced Science and Technology, The University of Tokyo Vivek Dogra Shanghai Center for Plant Stress Biology, Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences Martin Scholz Institute of Plant Biology and Biotechnology, University of Münster Guoxian Zhang Institute of Plant Science and Resources (IPSR), Okayama University Catherine de Vitry Institut de Biologie Physico-Chimique, Unité Mixte de Recherche 7141, Centre National de la Recherche Scientifique and Sorbonne Université Pierre et Marie Curie Hiroshi Ishikita Research Center for Advanced Science and Technology, The University of Tokyo Chanhong Kim Shanghai Center for Plant Stress Biology, Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences Michael Hippler Institute of Plant Science and Resources (IPSR), Okayama University Yuichiro Takahashi Research Institute for Interdisciplinary Science, Okayama University Wataru Sakamoto Institute of Plant Science and Resources (IPSR), Okayama University Photosynthesis is one of the most important reactions for sustaining our environment. Photosystem II (PSII) is the initial site of photosynthetic electron transfer by water oxidation. Light in excess, however, causes the simultaneous production of reactive oxygen species (ROS), leading to photo-oxidative damage in PSII. To maintain photosynthetic activity, the PSII reaction center protein D1, which is the primary target of unavoidable photo-oxidative damage, is efficiently degraded by FtsH protease. In PSII subunits, photo-oxidative modifications of several amino acids such as Trp have been indeed documented, whereas the linkage between such modifications and D1 degradation remains elusive. Here, we show that an oxidative post-translational modification of Trp residue at the N-terminal tail of D1 is correlated with D1 degradation by FtsH during high-light stress. We revealed that Arabidopsis mutant lacking FtsH2 had increased levels of oxidative Trp residues in D1, among which an N-terminal Trp-14 was distinctively localized in the stromal side. Further characterization of Trp-14 using chloroplast transformation in Chlamydomonas indicated that substitution of D1 Trp-14 to Phe, mimicking Trp oxidation enhanced FtsH-mediated D1 degradation under high light, although the substitution did not affect protein stability and PSII activity. Molecular dynamics simulation of PSII implies that both Trp-14 oxidation and Phe substitution cause fluctuation of D1 N-terminal tail. Furthermore, Trp-14 to Phe modification appeared to have an additive effect in the interaction between FtsH and PSII core in vivo. Together, our results suggest that the Trp oxidation at its N-terminus of D1 may be one of the key oxidations in the PSII repair, leading to processive degradation by FtsH. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0093-691X 210 2023 Negative correlations of mitochondrial DNA copy number in commercial frozen bull spermatozoa with the motility parameters after thawing 154 161 EN Hai Thanh Nguyen Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University Son Quang Do Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University Hiroshi Kobayashi Okayama Prefectural Center for Animal Husbandry and Research Takuya Wakai Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University Hiroaki Funahashi Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University The purpose of the current study was to investigate the relationship between mitochondrial content of commercial frozen-thawed bull spermatozoa and motility. Firstly, mitochondrial DNA copy number per spermatozoon (MDCN), mitochondrial content (MC), the percentage of spermatozoa with high mitochondrial membrane potential (HMMP), intracellular reactive oxygen species (ROS) and motility parameters of frozen-thawed spermatozoa derived from five bulls were determined by using qPCR, flow cytometry and CASA, respectively, and analyzed the relationships. Results showed that all parameters examined, including MDCN, MC, HMMP, ROS and motility indicators, significantly differed among frozen spermatozoa from different bulls. Both MDCN and MC were negatively correlated with HMMP and motility indicators, but positively with ROS, of course, whereas there was a highly positive relationship between MDCN and MC. Secondly, when MDCN and MC were examined in frozen spermatozoa prepared at different points in the lives of four bulls, those did not correlate overall throughout their lives (1.3–14.3 years old), but did correlate significantly in two sires. From these results, we conclude that MDCN and MC of frozen spermatozoa differ among sires, and are negatively correlated with HMMP and sperm motility parameters, probably due to mitochondrial oxidative stress resulted in the presence of ROS, demonstrating that these appear to be useful markers to assess sires’ spermatozoa. It should be noted that the MDCN and MC of bull spermatozoa may not vary overall with the age of the sire, whereas those changes with age in some individuals and may affect sperm motility. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2666-5018 4 10 2023 Syncope and loss of consciousness after implantation of a cardioverter-defibrillator in patients with Brugada syndrome: Prevalence and characteristics in long-term follow-up 641 649 EN Saori Asada Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomofumi Mizuno Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuro Masuda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akira Ueoka Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masakazu Miyamoto Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Kawada Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Nakagawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiro Nishii Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Syncope is a significant prognostic factor in patients with Brugada syndrome (BrS). However, the risk of ventricular arrhythmia in patients with nonarrhythmic loss of consciousness (LOC) is similar to that in asymptomatic patients. LOC events after implantable cardioverter-defibrillator (ICD) implantation may provide insights into underlying causes of the initial LOC episode. Objective The purpose of this study was to examine LOC characteristics following ICD implantation. Methods We retrospectively analyzed 112 patients with BrS (mean age 47 years; 111 men) who were treated with an ICD. The patients were classified into 3 groups based on symptoms at implantation: asymptomatic (35 patients); LOC (46 patients); and ventricular tachyarrhythmia (VTA) (31 patients). We evaluated the incidence and cause of LOC during long-term follow-up after ICD implantation. Results During mean follow-up of 12.2 years, 41 patients (37%) experienced LOC after ICD implantation. Arrhythmic LOC occurred in 5 asymptomatic patients, 14 LOC patients, and 16 patients with VTA. Nonarrhythmic LOC, similar to the initial episode, occurred after ICD implantation in 6 patients with prior LOC (2 with neurally mediated syncope and 4 with epilepsy). Most epileptic patients experienced LOC during rest or sleeping, and did not show an abnormal encephalogram during initial evaluation of the LOC episodes. Conclusion After ICD implantation, 13% of patients had nonarrhythmic LOC similar to the initial episode. Accurate classification of LOC based on a detailed medical history is important for risk stratification, although distinguishing arrhythmic LOC from epilepsy-related LOC episodes can be challenging depending on the circumstances and characteristics of the LOC event. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2666-5204 15 2023 Collapse-related traumatic intracranial hemorrhage following out-of-hospital cardiac arrest: A multicenter retrospective cohort study 100418 EN Fumiya Inoue Department of Emergency Medicine, Hiroshima City Hospital Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshihisa Ichiba Department of Emergency Medicine, Hiroshima City Hospital Takayuki Otani Department of Emergency Medicine, Hiroshima City Hospital Hiroshi Naito Department of Emergency Medicine, Hiroshima City Hospital Yoshinori Kosaki Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuya Murakami Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atsuyoshi Iida Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: Sudden loss of consciousness as a result of cardiac arrest can cause severe traumatic head injury. Collapse-related traumatic intracranial hemorrhage (CRTIH) following out-of-hospital cardiac arrest (OHCA) may be linked to poor neurological outcomes; however, there is a paucity of data on this entity. This study aimed to investigate the frequency, characteristics, and outcomes of CRTIH following OHCA. Methods: Adult patients treated post-OHCA at 5 intensive care units who had head computed tomography (CT) scans were included in the study. CRTIH following OHCA was defined as a traumatic intracranial injury from collapse due to sudden loss of consciousness associated with OHCA. Patients with and without CRTIH were compared. The primary outcome assessed was the frequency of CRTIH following OHCA. Additionally, the clinical features, management, and consequences of CRTIH were analyzed descriptively. Results: CRTIH following OHCA was observed in 8 of 345 enrolled patients (2.3%). CRTIH was more frequent after collapse outside the home, from a standing position, or due to cardiac arrest with a cardiac etiology. Intracranial hematoma expansion on follow up CT was seen in 2 patients; both received anticoagulant therapy, and one required surgical evacuation. Three patients (37.5%) with CRTIH had favorable neurological outcomes 28 days after collapse. Conclusions: Despite its rare occurrence, physicians should pay special attention to CRTIH following OHCA during the post-resuscitation care period. Larger prospective studies are warranted to provide a more explicit picture of this clinical condition. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1045-3873 35 2 2023 Significant delayed conduction and characteristic ventricular tachycardias in patients with cardiac sarcoidosis and electrical storm 307 316 EN Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Nakagawa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Akira Ueoka Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Tomofumi Mizuno Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Takuro Masuda Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Saori Asada Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Masakazu Miyamoto Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Satoshi Kawada Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Nobuhiro Nishii Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry Introduction: Electrical storm (ES) of ventricular tachyarrhythmias (VTAs) is an important cause of sudden death in patients with cardiac sarcoidosis (CS). VTAs in CS are associated with myocardial scarring and inflammation. However, little is known about the risk factors of ES in patients with CS and VTAs. The objective of this study is to clarify the characteristics and risk factors for the development of ES in patients with CS. Methods: The study population included consecutive 52 patients with CS and sustained VTA. Twenty-five out of 52 patients experienced ES. We evaluated clinical characteristics, imaging modalities, and electrocardiogram (ECG) parameters to determine the risk factors associated with ES. Results: Half of the patients experienced VTAs as the initial symptom of sarcoidosis, and eight patients had ES as the initial VTA episode. There were no differences in cardiac imaging abnormalities between patients with and without ES. Among ECG markers, significant QRS fragmentation (odds ratio [OR]: 7.9, p = .01) and epsilon waves (OR: 12.24, p = .02) were associated with ES. Among the ventricular tachycardia (VT) characteristics, multiple morphologies of monomorphic VTs (OR: 10.9, p < .01), short VT cycle lengths (OR: 12.5, p < .01), and polymorphic VT (OR: 13.5, p < .01) were associated with ES. Bidirectional VTs were detected in 10 patients with ES and one patient without ES. Immunosuppressive therapy relieved ES in some patients. Conclusions: ES was common in patients with CS and VTAs. Significant depolarization abnormalities that appeared as QRS fragmentation, epsilon waves, and specific VT characteristics were associated with ES. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 24 24 2023 Positive Regulation of S-Adenosylmethionine on Chondrocytic Differentiation via Stimulation of Polyamine Production and the Gene Expression of Chondrogenic Differentiation Factors 17294 EN Loc Dinh Hoang Advanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eriko Aoyama Advanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Miki Hiasa Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Omote Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Kubota Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuo Kuboki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaharu Takigawa Advanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences S-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate the expression of differentiated phenotype of chondrocytes. We also found that the cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2, and chondroitin sulfate biosynthetic enzymes. The blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, Alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 135 3 2023 医学における「ビジュアルアート教育」の展開：第４ステップ― 医学教育に必要な“気づき”を与える授業― 152 157 EN Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Okayama University Hospital Mikako Obika Department of General Medicine, Okayama University Hospital Takuya Kubo Department of Emergency and Critical Care Medicine, Okayama University Hospital Masumi Otsuka OTSUKA DESIGN Co., Ltd. Yuko Okamoto Okayama Prefectural Museum of Art Koh Fukutomi Okayama Prefectural Museum of Art Hiroshi Matsumoto Department of Plastic and Reconstructive Surgery, Okayama University Hospital 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 建白書ヲ読ミテ ―識語の語るもの― 290 298 EN Hiroshi YAMASHITA 資料紹介 (Materials and data) 10.18926/66200 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.

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 Decreased expression of hyaluronan synthase and loss of hyaluronan-rich cells in the anterior tibial fascia of the rat model of chemotherapy-induced peripheral neuropathy EN RUILIN WANG 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 Cardiopulmonary Resuscitation May Not Stop Glutamate Release in the Cerebral Cortex EN Miki FUSHIMI 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 RNA Editing is a Valuable Biomarker for Predicting Carcinogenesis in Ulcerative Colitis EN Kazutaka TAKAHASHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

岡山大学経済学会 Acta Medica Okayama 2433-4146 55 2 2023 地方公共サービス革新プロセスの視座の構築 1 14 EN Daiji Fujii Hiroshi Kanaji 10.18926/OER/66033 　When local governments develop public services, they often experience innovation processes. More often, the innovation processes referred to here seem to be the perceived needs for transformation faced with external pressures and the purposive responses to them. This article tries to depict this discourse from a different viewpoint. One of the perspectives that has been proposed so far is that the external environments are made up of multiple actors, and that the historical backgrounds and the relationships between these actors affect the structure of administrative organizations and the methods of providing public services. The transformation processes could be one-time events no matter how long the processes may take, but this article tries to argue they may connote a circular mechanism where both of the administrative organizations and the external actors feedback to each other. In order to elaborate this direction of theorizing, three steps are employed by applying existent literature of various types developed in rather a broader context of social sciences. First, if one of the goals of postmodern theorization is liberating the psychological energies of actors from the cramped social reality that structuralists postulated, then Actor-Network-Theory may be useful. Second, according to Sarasbathy’s research on entrepreneurial behaviors, the view that we effectuate our future through what we can do now is attractive in order to create a new discourse of social innovations, where we appreciate them as not springing out of nowhere all of sudden. Third, once this article accepts polyphonic views on social realities where congested discourses interact during abovementioned process, the role of civic entrepreneurs on the frontline can never be overstated enough. This is because such civic entrepreneurs could cooperate with minority opinions and raise them into broader contexts of dialogues within societies. No potential conflict of interest relevant to this article was reported.

IOP Publishing Acta Medica Okayama 0953-2048 35 5 2022 Experiment and numerical simulation of the combined effect of winding, cool-down, and screening current induced stresses in REBCO coils 054001 EN Hiroshi Ueda Graduate School of Natural Science and Technology, Okayama University Hideaki Maeda Japan Science and Technology Agency Yu Suetomi RIKEN Center for Biosystems Dynamics Research Yoshinori Yanagisawa RIKEN Center for Biosystems Dynamics Research This paper overviews the combined effects of winding, cool-down, and screening current-induced stresses in REBCO coils. First, a simulation method to model the circumferential stress modification effect due to the screening-current is overviewed. The simulation includes coil winding, cooling down, and coil charge up to the operating current. Second, we will compare the numerical simulation results with the experimental results. The numerical simulations for a dry coil and an epoxy impregnated coil agree well with the experimental results. Third, the enhanced circumferential stress did not degrade the performance of a dry winding REBCO coil, but the improved increased compressive stress buckled the coil structure. Finally, it is demonstrated that epoxy impregnation has beneficial effects in reducing the stress modification effect. However, the circumferential stress is enormously enhanced at the coil ends, sometimes resulting in degradation of the coil performance. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry Acta Medica Okayama 2041-6520 14 42 2023 An emissive charge-transfer excited-state at the well-defined hetero-nanostructure interface of an organic conjugated molecule and two-dimensional inorganic nanosheet 11914 11923 EN Tomokazu Umeyama Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo Daizu Mizutani Department of Molecular Engineering, Graduate School of Engineering, Kyoto University Yuki Ikeda Department of Molecular Engineering, Graduate School of Engineering, Kyoto University W. Ryan Osterloh Department of Molecular Engineering, Graduate School of Engineering, Kyoto University Futa Yamamoto Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo Kosaku Kato Graduate School of Natural Science and Technology, Okayama University Akira Yamakata Graduate School of Natural Science and Technology, Okayama University Masahiro Higashi Department of Molecular Engineering, Graduate School of Engineering, Kyoto University Takumi Urakami Department of Molecular Engineering, Graduate School of Engineering, Kyoto University Hirofumi Sato Department of Molecular Engineering, Graduate School of Engineering, Kyoto University Hiroshi Imahori Department of Molecular Engineering, Graduate School of Engineering, Kyoto University Precise engineering of excited-state interactions between an organic conjugated molecule and a two-dimensional semiconducting inorganic nanosheet, specifically the manipulation of charge-transfer excited (CTE) states, still remains a challenge for state-of-the-art photochemistry. Herein, we report a long-lived, highly emissive CTE state at structurally well-defined hetero-nanostructure interfaces of photoactive pyrene and two-dimensional MoS2 nanosheets via an N-benzylsuccinimide bridge (Py-Bn-MoS2). Spectroscopic measurements reveal that no charge-transfer state is formed in the ground state, but the locally-excited (LE) state of pyrene in Py-Bn-MoS2 efficiently generates an unusual emissive CTE state. Theoretical studies elucidate the interaction of MoS2 vacant orbitals with the pyrene LE state to form a CTE state that shows a distinct solvent dependence of the emission energy. This is the first example of organic-inorganic 2D hetero-nanostructures displaying mixed luminescence properties by an accurate design of the bridge structure, and therefore represents an important step in their applications for energy conversion and optoelectronic devices and sensors. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0003-9969 155 2023 Ruxolitinib altered IFN-β induced necroptosis of human dental pulp stem cells during osteoblast differentiation 105797 EN Atsuko Tanaka Department of Orthodontics, Okayama University Hospital Satoru Hayano Department of Orthodontics, Okayama University Hospital Masayo Nagata Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takahiro Kosami Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ziyi Wang Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Kamioka Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objective: This study aimed to evaluate the role of ruxolitinib in the interferon beta (IFN-β) mediated osteoblast differentiation using human dental pulp stem cells (hDPSCs). Design: hDPSCs from five deciduous teeth of healthy patients were stimulated by adding human recombinant IFN-β protein (1 or 2 ng/ml) to the osteogenic differentiation induction medium. Substrate formation was determined using Alizarin Red staining, calcium concentration, and osteoblast marker expression levels. Ruxolitinib was used to inhibit the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway. Apoptosis was detected using terminal deoxynucleotidyl nick-end labeling (TUNEL) staining, and necroptosis was detected using propidium iodide staining and phosphorylated mixed lineage kinase domain-like protein (pMLKL) expression. Results: In the IFN-β-treated group, substrate formation was inhibited by a reduction in alkaline phosphatase (ALP) expression in a concentration-dependent manner. Although the proliferation potency was unchanged between the IFN-β-treated and control groups, the cell number was significantly reduced in the experimental group. TUNEL-positive cell number was not significantly different; however, the protein level of necroptosis markers, interleukin-6 (IL-6) and pMLKL were significantly increased in the substrate formation. Cell number and ALP expression level were improved in the group administered ruxolitinib, a JAK-STAT inhibitor. Additionally, ruxolitinib significantly suppressed IL-6 and pMLKL levels. Conclusion: Ruxolitinib interfered with the IFN-β-mediated necroptosis and osteogenic differentiation via the JAK-STAT pathway. 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 Relationship of Intraoperative SpO2 and ETCO2 Values with Postoperative Hypoxemia in Elderly Patients after Non-Cardiac Surgery 537 543 EN Qingqing Song Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yu Pan Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Kanazawa Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65976 Elderly patients are at higher risk of postoperative hypoxemia due to their decreased respiratory function. The aim of this study was to investigate the relationship of intraoperative oxygen saturation (SpO2) and end-expiratory carbon dioxide (ETCO2) values with postoperative hypoxemia in elderly patients. The inclusion criteria were: 1) patients aged≥75 years; 2) underwent general anesthesia in non-cardiac surgery; 3) operative time longer than two hours; and 4) admission to the intensive care unit (ICU) following surgery performed between January and December 2019. Intraoperative SpO2 and ETCO2 values were collected every minute for the first two hours during surgery. The 253 patients were divided into two groups: SpO2≥92% and SpO2<92%. The time-weighted averages of intraoperative SpO2 and ETCO2 were used to compare differences between the two groups. The incidence of postoperative hypoxemia was 22.5%. For similar ventilator settings, patients with postoperative hypoxemia had lower intraoperative SpO2 and higher ETCO2 values. Sex, ASA classification, and intraoperative SpO2 were independent risk factors for postoperative hypoxemia. In conclusion, postoperative SpO2<92% was a frequent occurrence (> 20%) in elderly patients who underwent major non-cardiac surgery. Postoperative hypoxemia was associated with low intraoperative SpO2 and relatively higher ETCO2. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Neurological Analysis Based on the Terminal End of the Spinal Cord and the Narrowest Level of Injured Spine in Thoracolumbar Spinal Injuries 499 509 EN Yuji Hatakeyama Department of Orthopaedic Surgery, Akita Red Cross Hospital Michio Hongo Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Tadato Kido Department of Orthopaedic Surgery, Akita Rosai Hospital Masakazu Urayama Department of Orthopaedic Surgery, Ogachi Central Hospital Yuji Kasukawa Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Hiroshi Sasaki Department of Orthopaedic Surgery, Noshiro Kousei Medical Center Toshiaki Aizawa Department of Orthopaedic Surgery, Kitaakita Municipal Hospital Daisuke Kudo Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Ryota Kimura Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Yuichi Ono Department of Orthopaedic Surgery, Akita Red Cross Hospital Fumihito Kasama Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Naohisa Miyakoshi Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Original Article 10.18926/AMO/65972 This study aimed to clarify neurological differences among the epiconus, conus medullaris, and cauda equina syndromes. Eighty-seven patients who underwent surgery for acute thoracolumbar spinal injuries were assessed. We defined the epiconus as the region from the terminal end of the spinal cord to the proximal 1.0 to 2.25 vertebral bodies, the conus medullaris as the region proximal to < 1.0 vertebral bodies, and the cauda equina as the distal part of the nerve roots originating from the spinal cord. On the basis of the distance from the terminal end of the spinal cord to the narrowest level of the spinal canal, the narrowest levels were ordered as follows: the epiconus followed by the conus medullaris and cauda equina. The narrowest levels were the epiconus in 22 patients, conus medullaris in 37 patients, and cauda equina in 25 patients. On admission, significantly more patients had a narrowed epiconus of Frankel grades A-C than a narrowed cauda equina. At the final follow-up, there were no significant differences in neurological recovery among those with epiconus, conus medullaris, or cauda equina syndrome. Anatomically classifying the narrowest lesion is useful for clarifying the differences and similarities among these three syndromes. 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 Does Participation in the Setouchi Triennale Foster Social Capital? : A Cross-Sectional Study 443 449 EN Chikara Miyaji 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 Hiroshi Habu 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 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, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Original Article 10.18926/AMO/65966 This study examined whether participation in an art project was associated with higher social capital (SC). We conducted a questionnaire survey from November 2021 to March 2022 among residents aged 20 years or older of Naoshima, an island in Kagawa Prefecture, Japan. Before the survey, the Setouchi Triennale had been held on Naoshima four times, starting in 2010. We calculated propensity scores for Triennale participation and performed propensity score matching. We then compared cognitive and structural SC by Triennale participation and found significant differences, respectively. We adopted a conditional ordered logistic regression analysis with propensity score matching for cognitive or structural SC, and found adjusted odd ratios of 2.913 (95%CI, 1.846-4.596) for cognitive SC and 4.535 (95%CI, 2.839-7.244) for structural SC. Our findings suggest that Triennale participation enhanced the cognitive aspect of SC while also building structural SC. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0022-2623 65 8 2022 Identification of a Vitamin-D Receptor Antagonist, MeTC7, which Inhibits the Growth of Xenograft and Transgenic Tumors In Vivo 6039 6055 EN Negar Khazan Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Kyu Kwang Kim Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Jeanne N. Hansen Department of Pediatrics, University of Rochester Medical Center Niloy A. Singh Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Taylor Moore Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Cameron W. A. Snyder Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Ravina Pandita Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Myla Strawderman Department of Biostatistics and Computational Biology, University of Rochester Medical Center Michiko Fujihara 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 Ye Jian Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center Nicholas Battaglia Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center Naohiro Yano Department of Surgery, Division of Surgical Research, Rhode Island Hospital, Alpert Medical School of Brown University Yuki Teramoto Department of Pathology and Laboratory Medicine, University of Rochester Medical Center Leggy A. Arnold Department of Chemistry and Biochemistry, University of Wisconsin Milwaukee Russell Hopson Department of Chemistry, Brown University Keshav Kishor Department of Chemistry, Birla Institute of Technology Sneha Nayak Department of Chemistry, Birla Institute of Technology Debasmita Ojha Department of Chemistry, Birla Institute of Technology Ashoke Sharon Department of Chemistry, Birla Institute of Technology John M. Ashton Genomics Core Facility, Wilmot Cancer Center, University of Rochester Medical Center Jian Wang Department of Pharmacology and Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Penn State University Michael T. Milano Department of Radiation Oncology, University of Rochester Medical Center Hiroshi Miyamoto Department of Pathology and Laboratory Medicine, University of Rochester Medical Center David C. Linehan Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center Scott A. Gerber Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center Nada Kawar Center for Breast Health and Gynecologic Oncology, Mercy Medical Center Ajay P. Singh Rutgers, The State University of New Jersey Erdem D. Tabdanov CytoMechanobiology Laboratory, Department of Pharmacology, Penn State College of Medicine, Pennsylvania State University Nikolay V. Dokholyan Department of Pharmacology and Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Penn State University Hiroki Kakuta Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Peter W. Jurutka School of Mathematical and Natural Sciences, Arizona State University, Health Futures Center Nina F. Schor Departments of Pediatrics, Neurology, and Neuroscience, University of Rochester Medical Center Rachael B. Rowswell-Turner Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Rakesh K. Singh Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Richard G. Moore Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Vitamin-D receptor (VDR) mRNA is overexpressed in neuroblastoma and carcinomas of lung, pancreas, and ovaries and predicts poor prognoses. VDR antagonists may be able to inhibit tumors that overexpress VDR. However, the current antagonists are arduous to synthesize and are only partial antagonists, limiting their use. Here, we show that the VDR antagonist MeTC7 (5), which can be synthesized from 7-dehydrocholesterol (6) in two steps, inhibits VDR selectively, suppresses the viability of cancer cell-lines, and reduces the growth of the spontaneous transgenic TH-MYCN neuroblastoma and xenografts in vivo. The VDR selectivity of 5 against RXRα and PPAR-γ was confirmed, and docking studies using VDR-LBD indicated that 5 induces major changes in the binding motifs, which potentially result in VDR antagonistic effects. These data highlight the therapeutic benefits of targeting VDR for the treatment of malignancies and demonstrate the creation of selective VDR antagonists that are easy to synthesize. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0177-7971 134 1 2022 Data-driven model of the local wind field over two small lakes in Jyväskylä, Finland 18 EN Takayuki Shuku Graduate School of Environmental and Life Science, Okayama University Janne Ropponen Finnish Environment Institute SYKE, Jyväskylä Office Janne Juntunen Finnish Environment Institute SYKE, Jyväskylä Office Hiroshi Suito Advanced Institute for Materials Research (AIMR), Tohoku University This study presents a data-driven model of the local wind field over two small lakes in Jyväskylä, Finland. Five temporary monitoring stations installed during the summers of 2015 and 2016 observed wind speed/direction around the two lakes. In addition, an official meteorological station located 15 km north of the lakes is permanently available. Our goal was to develop a model that could evaluate wind speed and direction over the two lakes using only data from the permanent station. Statistical analysis for the spatio-temporal wind data revealed that (1) local wind speed is correlated with the elevation and its cyclic pattern is identical to that of the official-station data, and (2) the local wind direction field is spatially homogeneous and is strongly correlated with the official-station data. Based on these results, we built two regression models for estimating spatial distribution of local wind speed and directions based on the digital elevation model (DEM) and official-station data. We compared the predicted wind speeds/directions by the proposed model with the corresponding observation data and a numerical result for model validation. We found that the proposed model could effectively simulate heterogeneous local wind fields and considers uncertainty of estimates. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2045-8932 13 3 2023 Impact of malnutrition on prognosis in patients with pulmonary arterial hypertension e12286 EN Mitsutaka Nakashima Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura 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 Pulmonary arterial hypertension is a life-threatening disease that coexists with right heart failure. We evaluated the relationship between malnutrition and prognosis in patients with pulmonary arterial hypertension, as malnutrition is known as a prognosis determinant in chronic heart failure. We retrospectively reviewed data of patients with pulmonary arterial hypertension before treatment. The Geriatric Nutritional Risk Index, Prognostic Nutritional Index, and Controlling Nutritional Status scores on the day of diagnosis were calculated to assess the nutritional status. Clinical endpoints were defined as composite outcomes of all-cause death or lung transplantation. Eighty patients were enrolled (mean age, 50 years; 23 men). The mean pulmonary arterial pressure was 47 ± 19 mmHg, Geriatric Nutritional Risk Index was 99.9 ± 12.0, and Prognostic Nutritional Index was 46.3 ± 10.0. The median Controlling Nutritional Status score was 2 (1–4). During the median 5.5-year follow-up period, 28 composite events occurred. Kaplan-Meier analysis demonstrated significant differences in the incidence of clinical endpoints between groups divided by each median Geriatric Nutritional Risk Index, Prognostic Nutritional Index, and Controlling Nutritional Status score (p = 0.007, 0.039, and 0.010, respectively). In multivariate Cox regression analysis, clinical endpoints were significantly associated with Geriatric Nutritional Risk Index (hazard ratio: 0.953, 95% confidence interval: 0.918–0.990), Prognostic Nutritional Index (hazard ratio: 0.942, 95% confidence interval: 0.892–0.996), and Controlling Nutritional Status score (hazard ratio: 1.230, 95% confidence interval: 1.056–1.433) after adjustment for factors associated in univariate Cox regression analysis. Malnutrition at diagnosis is a useful prognostic predictor for patients with pulmonary arterial hypertension. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2053-8790 9 1 2022 Association of one-point glucocorticoid-free status with chronic damage and disease duration in systemic lupus erythematosus: a cross-sectional study e000772 EN Ken-ei Sada 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 Yosuke Asano 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 Yoshia Miyawaki Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Keiji Ohashi 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 Takayuki 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 Yoshinori Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Ryusuke Yoshimi Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine Yasuhiro Shimojima Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine Shigeru Ohno Center for Rheumatic Diseases, Yokohama City University Medical Center Hiroshi Kajiyama Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University Kunihiro Ichinose Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Shuzo Sato Department of Rheumatology, Fukushima Medical University School of Medicine Michio Fujiwara Department of Rheumatology, Yokohama Rosai Hospital Nobuyuki Yajima Division of Rheumatology, Department of Medicine, Showa University School of Medicine Objective　It is still unclear how glucocorticoids (GCs) affect the long-term clinical course of patients with SLE. The objective of this study is to explore the factors associated with GC-free treatment status. Methods　Using data from the lupus registry of nationwide institutions, GC dose at registration was compared between short, middle and long disease durations of <5, 5–20 and ≥20 years, respectively. After excluding patients who never used GC, we evaluated the relationship between GC-free status and chronic damage using Systemic Lupus International Collaborating Clinics Damage Index. Results　GC doses at enrolment of the 1019 patients were as follows: GC-free in 101 (10%); 0<prednisolone (PSL) ≤5 mg/day in 411 (40%); 5<PSL ≤7.5 in 169 (17%); 7.5<PSL ≤10 in 194 (19%) and PSL≥10 in 144 (14%) patients. Of the patients who were not currently using GCs, patients who never used GC more frequently had short disease duration (66% with short, 23% with middle and 17% with long disease duration, p=0.00029). Univariate analysis of patients who underwent GC treatment showed that patients without GCs exhibited older age, lower disease activity, less immunosuppressant and hydroxychloroquine use and higher C3 levels. Among patients with a disease duration of ≥20 years, GC-free status was more frequent in patients without chronic damage (11% vs 4%, p=0.023). After adjusting for age, sex and disease activity, no chronic damage accrual was associated with GC-free status (OR 3.6, 95% CI 1.1 to 11.3). Conclusion　Even in the patients with long disease duration, one-point GC-free treatment status might be related to no chronic damage accrual. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 2297-055X 10 2023 In vivo tracking transplanted cardiomyocytes derived from human induced pluripotent stem cells using nuclear medicine imaging 1261330 EN Yukihiro Saito Department of Cardiovascular Medicine, Okayama University Hospital Naoko Nose Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshihiro Iida Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kaoru Akazawa Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayuki Kanno Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Fujimoto Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takanori Sasaki Okayama Medical Innovation Center, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Masaru Akehi Okayama Medical Innovation Center, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Higuchi Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Akagi Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masashi Yoshida Department of Chronic Kidney Disease and Cardiovascular Disease, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Miyoshi Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Ito Department of General Internal Medicine 3, Kawasaki Medical School Kazufumi Nakamura Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Introduction: Transplantation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is a promising treatment for heart failure. Information on long-term cell engraftment after transplantation is clinically important. However, clinically applicable evaluation methods have not yet been established. Methods: In this study, to noninvasively assess transplanted cell engraftment, human SLC5A5, which encodes a sodium/iodide symporter (NIS) that transports radioactive tracers such as 125I, 18F-tetrafluoroborate (TFB), and 99mTc-pertechnetate (99mTcO4－), was transduced into human induced pluripotent stem cells (iPSCs), and nuclear medicine imaging was used to track engrafted human iPSC-CMs. Results: To evaluate the pluripotency of NIS-expressing human iPSCs, they were subcutaneously transplanted into immunodeficient rats. Teratomas were detected by 99mTcO4－ single photon emission computed tomography (SPECT/CT) imaging. NIS expression and the uptake ability of 125I were maintained in purified human iPSC-CMs. NIS-expressing human iPSC-CMs transplanted into immunodeficient rats could be detected over time using 99mTcO4－ SPECT/CT imaging. Unexpectedly, NIS expression affected cell proliferation of human iPSCs and iPSC-derived cells. Discussion: Such functionally designed iPSC-CMs have potential clinical applications as a noninvasive method of grafted cell evaluation, but further studies are needed to determine the effects of NIS transduction on cellular characteristics and functions. No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 183 2023 サー・ウィリアム・テンプルの初期著作 ― ロマンス ― 29 37 EN Hiroshi KISHIMOTO Faculty of Education, Okayama University 10.18926/bgeou/65923 　サー・ウィリアム・テンプルは，グランド・ツアーの滞在先で９編のロマンスを書いている。テンプル最初期の著作である。いずれも短編で，フランソワ・ド・ロセの『現代悲劇物語』の翻案である。そのうち，現在読むことができるのは５編のみである。文学作品として見た場合，物語のプロットや人物造形が単純かつ類型的で，多くの欠点が目立つ。しかしたとえ稚拙なものであろうとも，それら若書きの作品の中に，創作していたときのテンプルの内面をのぞき見ることができる。そこには，恋人ドロシー・オズボーンとの仲を引き裂かれ，大陸の旅先で悶々とした日々を送っていたテンプルのやり場のない感情が込められているのである。本稿は，22 歳前後に書かれた散文ロマンスをテンプルの伝記の中に位置づけ，それと関連づけながら読む必要があることを明らかにした。 No potential conflict of interest relevant to this article was reported.

American Association for the Advancement of Science (AAAS) Acta Medica Okayama 2375-2548 8 24 2022 Amphotericin B assembles into seven-molecule ion channels: An NMR and molecular dynamics study eabo2658 EN Yuichi Umegawa Department of Chemistry, Graduate School of Science, Osaka University Tomoya Yamamoto Department of Chemistry, Graduate School of Science, Osaka University Mayank Dixit Department of Materials Chemistry, Graduate School of Engineering, Nagoya University Kosuke Funahashi Department of Materials Chemistry, Graduate School of Engineering, Nagoya University Sangjae Seo Department of Materials Chemistry, Graduate School of Engineering, Nagoya University Yasuo Nakagawa Department of Chemistry, Graduate School of Science, Osaka University Taiga Suzuki Department of Chemistry, Graduate School of Science, Osaka University Shigeru Matsuoka Department of Chemistry, Graduate School of Science, Osaka University Hiroshi Tsuchikawa Department of Chemistry, Graduate School of Science, Osaka University Shinya Hanashima Department of Chemistry, Graduate School of Science, Osaka University Tohru Oishi Department of Chemistry, Graduate School of Science, Osaka University Nobuaki Matsumori Department of Chemistry, Graduate School of Science, Osaka University Wataru Shinoda Research Institute for Interdisciplinary Science, Okayama University Michio Murata Department of Chemistry, Graduate School of Science, Osaka University Amphotericin B, an antifungal drug with a long history of use, forms fungicidal ion-permeable channels across cell membranes. Using solid-state nuclear magnetic resonance spectroscopy and molecular dynamics simulations, we experimentally elucidated the three-dimensional structure of the molecular assemblies formed by this drug in membranes in the presence of the fungal sterol ergosterol. A stable assembly consisting of seven drug molecules was observed to form an ion conductive channel. The structure is somewhat similar to the upper half of the barrel-stave model proposed in the 1970s but substantially different in the number of molecules and in their arrangement. The present structure explains many previous findings, including structure-activity relationships of the drug, which will be useful for improving drug efficacy and reducing adverse effects. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2047-4873 28 18 2021 Incremental prognostic value of non-alcoholic fatty liver disease over coronary computed tomography angiography findings in patients with suspected coronary artery disease 2059 2066 EN Keishi Ichikawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Osawa Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center Takashi Miki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hironobu Toda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Yoshida 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 Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aims　This study aimed to investigate additional risk stratification benefits of hepatic steatosis (HS) concurrently assessed during coronary computed tomography angiography (CTA) in a large patient cohort with suspected stable coronary artery disease (CAD). Methods and results　In this prospective study, 1148 Japanese outpatients without a history of CAD who underwent coronary CTA for suspected stable CAD (mean age 64 ± 14 years) were included. HS, defined on CT as a hepatic-to-spleen attenuation ratio of <1.0, was examined just before the evaluation of adverse CTA findings, defined as obstructive and/or high-risk plaque. The major adverse cardiac events (MACE) were the composite of cardiac death, acute coronary syndrome, and late revascularization. The incremental predictive value of HS was evaluated using the global χ2 test and C-statistic. HS was identified in 247 (22%) patients. During a median follow-up of 3.9 years, MACE was observed in 40 (3.5%) patients. HS was significantly associated with MACE in a model that included adverse CTA findings (hazard ratio 4.01, 95% confidence interval 2.12–7.59, P < 0.001). By adding HS to the Framingham risk score and adverse CTA findings, the global χ2 score and C-statistic significantly increased from 29.0 to 49.5 (P < 0.001) and 0.74 to 0.81 (P = 0.026), respectively. In subgroup analyses in patients with diabetes mellitus and metabolic syndrome, HS had significant additive predictive value for MACE over the Framingham risk score and adverse CTA findings. Conclusion　In patients with suspected stable CAD, concurrent evaluation of HS during coronary CTA enables more accurate detection of patients at higher risk of MACE. 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. 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. 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). 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.

Institute of Mathematics, Polish Academy of Sciences Acta Medica Okayama 0016-2736 263 2023 The universal factorial Hall–Littlewood P- and Q-functions 133 166 EN Masaki Nakagawa Graduate School of Education Okayama University Hiroshi Naruse Graduate School of Education University of Yamanashi We introduce factorial analogues of the ordinary Hall–Littlewood P- and Q-polynomials, which we call the factorial Hall–Littlewood P- and Q-polynomials. Using the universal formal group law, we further generalize these polynomials to the universal factorial Hall–Littlewood P- and Q-functions. We show that these functions satisfy the vanishing property which the ordinary factorial Schur S-, P-, and Q-polynomials have. By the vanishing property, we derive the Pieri-type formula and a certain generalization of the classical hook formula. We then characterize our functions in terms of Gysin maps from flag bundles in complex cobordism theory. Using this characterization and Gysin formulas for flag bundles, we obtain generating functions for the universal factorial Hall–Littlewood P- and Q-functions. Using our generating functions, we show that our factorial Hall–Littlewood P- and Q-polynomials have a certain cancellation property. Further applications such as Pfaffian formulas for K-theoretic factorial Q-polynomials are also given. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 18 5 2023 Randomized phase II study of daily versus alternate-day administrations of S-1 for the elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm)-IIIA of non-small cell lung cancer: Setouchi Lung Cancer Group Study 1201 e0285273 EN Hiromasa Yamamoto Department of Thoracic Surgery, Okayama University Hospital Junichi Soh Department of Surgery, Division of Thoracic Surgery, Kindai University Faculty of Medicine Norihito Okumura Department of Thoracic Surgery, Kurashiki Central Hospital Hiroyuki Suzuki Department of Chest Surgery, Fukushima Medical University Hospital Masao Nakata Department of General Thoracic Surgery, Kawasaki Medical School Hospital Toshiya Fujiwara Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Kenichi Gemba Department of Respiratory Medicine, Chugoku Central Hospital Isao Sano Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital Takuji Fujinaga Department of General Thoracic Surgery, National Hospital Organization Nagara Medical Center Masafumi Kataoka Department of Surgery and Respiratory Center, Okayama Saiseikai General Hospital Yasuhiro Terazaki Department of Respiratory S0urgery, Saga-Ken Medical Centre Koseikan Nobukazu Fujimoto Department of Medical Oncology and Respiratory Medicine, Okayama Rosai Hospital Kazuhiko Kataoka Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center Shinji Kosaka Department of Thoracic Surgery, Shimane Prefectural Central Hospital Motohiro Yamashita Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center Hidetoshi Inokawa Department of Thoracic Surgery, National Hospital Organization Yamaguchi-Ube Medical Center Masaaki Inoue Department of Chest Surgery, Shimonoseki City Hospital Hiroshige Nakamura Division of General Thoracic Surgery, Tottori University Hospital Yoshinori Yamashita Department of Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Hospital Satoshi Morita Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine Keitaro Matsuo Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute Junichi Sakamoto Tokai Central Hospital Hiroshi Date Department of Thoracic Surgery, Kyoto University Hospital Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Background It is shown that the postoperative adjuvant chemotherapy for non-small cell lung cancer (NSCLC) was associated with survival benefit in an elderly population. We aimed to analyze the feasibility and efficacy of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm) to IIIA (UICC TNM Classification of Malignant Tumours, 7th edition) NSCLC. Methods Elderly patients were randomly assigned to receive adjuvant chemotherapy for one year consisting of either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Arm A) or a daily oral administration of S-1 (80 mg/m2/day) for 14 consecutive days followed by 7-day rest (Arm B). The primary endpoint was feasibility (treatment completion rate), which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more. Results We enrolled 101 patients in which 97 patients received S-1 treatment. The treatment completion rate at 6 months was 69.4% in Arm A and 64.6% in Arm B (p = 0.67). Treatment completion rate in Arm B tended to be lower compared to Arm A, as the treatment period becomes longer (at 9 and 12 months). RDI of S-1 at 12 months and completion of S-1 administration without dose reduction or postponement at 12 months was significantly better in Arm A than in Arm B (p = 0.026 and p < 0.001, respectively). Among adverse events, anorexia, skin symptoms and lacrimation of any grade were significantly more frequent in Arm B compared with Arm A (p = 0.0036, 0.023 and 0.031, respectively). The 5-year recurrence-free survival rates were 56.9% and 65.7% for Arm A and B, respectively (p = 0.22). The 5-year overall survival rates were 68.6% and 82.0% for Arm A and B, respectively (p = 0.11). Conclusion Although several adverse effects were less frequent in Arm A, both alternate-day and daily oral administrations of S-1 were demonstrated to be feasible in elderly patients with completely resected NSCLC. No potential conflict of interest relevant to this article was reported.

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

岡山医学会 Acta Medica Okayama 0030-1558 135 2 2023 オートファジー 92 94 EN Kohji Takei Department of Neurosience, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Yamada Department of Neurosience, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 135 2 2023 医学における「ビジュアルアート教育」の展開：第３ステップ― 岡山県立美術館の協力による対話型鑑賞の導入― 85 88 EN Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Okayama University Hospital Mikako Obika Department of General Medicine, Okayama University Hospital Takuya Kubo Department of Emergency and Critical Care Medicine, Okayama University Hospital Masumi Otsuka OTSUKA DESIGN Co., Ltd. Yuko Okamoto Okayama Prefectural Museum of Art Koh Fukutomi Okayama Prefectural Museum of Art Hiroshi Matsumoto Department of Plastic and Reconstructive Surgery, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 12 15 2023 Evidence for Hypoxia-Induced Shift in ATP Production from Glycolysis to Mitochondrial Respiration in Pulmonary Artery Smooth Muscle Cells in Pulmonary Arterial Hypertension 5028 EN Satoshi Akagi Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazufumi Nakamura Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Megumi Kondo Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Hirohata Department of Medical Technology, Graduate School of Health Sciences, Okayama University Heiichiro Udono Department of Immunology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Mikako Nishida Department of Immunology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yukihiro Saito Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masashi Yoshida Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Miyoshi Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Ito Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: The metabolic state of pulmonary artery smooth muscle cells (PASMCs) from patients with pulmonary arterial hypertension (PAH) is not well understood. In this study, we examined the balance between glycolysis and mitochondrial respiration in non-PAH-PASMCs and PAH-PASMCs under normoxia and hypoxia. Methods: We investigated the enzymes involved in glycolysis and mitochondrial respiration, and studied the two major energy-yielding pathways (glycolysis and mitochondrial respiration) by measuring extracellular acidification rate (ECAR) and cellular oxygen consumption rate (OCR) using the Seahorse extracellular flux technology. Results: Under both normoxia and hypoxia, the mRNA and protein levels of pyruvate dehydrogenase kinase 1 and pyruvate dehydrogenase were increased in PAH-PASMCs compared with non-PAH-PASMCs. The mRNA and protein levels of lactate dehydrogenase, as well as the intracellular lactate concentration, were also increased in PAH-PASMCs compared with non-PAH-PASMCs under normoxia. However, these were not significantly increased in PAH-PASMCs compared with non-PAH-PASMCs under hypoxia. Under normoxia, ATP production was significantly lower in PAH-PASMCs (59 ± 5 pmol/min) than in non-PAH-PASMCs (70 ± 10 pmol/min). On the other hand, ATP production was significantly higher in PAH-PASMCs (31 ± 5 pmol/min) than in non-PAH-PASMCs (14 ± 3 pmol/min) under hypoxia. Conclusions: There is an underlying change in the metabolic strategy to generate ATP production under the challenge of hypoxia. 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.

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

BMC Acta Medica Okayama 1471-2253 23 1 2023 Associations of systemic oxygen consumption with age and body temperature under general anesthesia: retrospective cohort study 216 EN Satoshi Kimura Department of Anesthesiology and Resuscitology, Okayama University Hospital Kazuyoshi Shimizu Department of Anesthesiology and Resuscitology, Okayama University Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Hospital Background　Body temperature (BT) is thought to have associations with oxygen consumption (VO2). However, there have been few studies in which the association between systemic VO2 and BT in humans was investigated in a wide range of BTs. The aims of this study were 1) to determine the association between VO2 and age and 2) to determine the association between VO2 and BT. Methods　This study was a retrospective study of patients who underwent surgery under general anesthesia at a tertiary teaching hospital. VO2 was measured by the Dräger Perseus A500 anesthesia workstation (Dräger Medical, Lubeck, Germany). The associations of VO2 with age and BT were examined using spline regression and multivariable regression analysis with a random effect. Results　A total of 7,567 cases were included in this study. A linear spline with one knot shows that VO2 was reduced by 2.1 ml/kg/min with one year of age (p < 0.001) among patients less than 18 years of age and that there was no significant change in VO2 among patients 18 years of age or older (estimate: 0.014 ml/kg/min, p = 0.08). VO2 in all bands of BT < 36.0 °C was not significantly different from VO2 in BT > = 36 °C and < 36.5 °C. Multivariable linear regression analysis showed that compared with VO2 in BT > = 36 °C and < 36.5 °C as a reference, VO2 levels were significantly higher by 0.57 ml/kg/min in BT > = 36.5 °C and < 37 °C (p < 0.001), by 1.8 ml/kg/min in BT > = 37 °C and < 37.5 °C (p < 0.001), by 3.6 ml/kg/min in BT > = 37.5 °C and < 38 °C (p < 0.001), by 4.9 ml/kg/min in BT > = 38 °C and < 38.5 °C (p < 0.001), and by 5.7 ml/kg/min in BT > = 38.5 °C (p < 0.001). The associations between VO2 and BT were significantly different among categorized age groups (p = 0.03). Conclusions　VO2 increases in parallel with increase in body temperature in a hyperthermic state but remains constant in a hypothermic state. Neonates and infants, who have high VO2, may have a large systemic organ response in VO2 to change in BT. No potential conflict of interest relevant to this article was reported.