岡山大学教育推進機構 教師教育開発センター Acta Medica Okayama 2186-1323 16 2026 大学院共通科目『リーダーシップとSDGs』の教育モデル構築と成果分析 理論学習・ピアレビュー・省察活動によるリーダーシップ教育の新展開 221 235 EN Mamoru ISHIDA Faculty of General Education and Global Studies, Okayama University Shinichi OTSUNE Graduate student, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takuya NAKAZAWA Graduate student, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University 10.18926/CTED/70371 　岡山大学大学院では、博士課程人材のリーダーシップ育成に向け、共通科目『リーダーシップとSDGs』を設計・実践している。本科目はSDGsに貢献するリーダー育成に主眼を置き、理論学習・ピアレビュー・省察・グループディスカッション等の手法を組み合わせ、学生同士の学び合い・自己成長の促進を目的としている。本稿では、学部・研究科ごとに学習成果を分析し、理論に基づく省察的学びと協働的な批評活動がリーダーシップ理解や成長に有用であることを明らかにした。本研究は、学術的理論と実践的活動を織り交ぜたモデル構築と、その継続的改善の意義を示している。 No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2192-4449 15 1 2026 A case of tubulointerstitial nephritis with infiltration of neutrophils and interleukin-17-positive cells associated with Behçet’s disease 35 EN Naruhiko Uchida 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 Natsuki Kubota 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 Katsuyuki Tanabe 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 Behçet’s disease (BD) is a non-infectious inflammatory condition characterized by neutrophilic infiltration. In addition to primary symptoms, including oral and genital ulcers, ocular involvement, and skin lesions, BD can also affect various organs. However, renal involvement, particularly in tubulointerstitial nephritis, has rarely been described. Herein, a rare case of acute tubulointerstitial nephritis in a patient clinically diagnosed with BD is reported. The renal lesion presented with other symptoms of BD and fever, and was considered to be BD-related due to the presence of neutrophilic infiltration and its responsiveness to BD-directed therapy. Alterations in T-helper (Th) 1, Th2, and Th17 cytokine profiles are associated with BD activity. Interleukin (IL)-17 plays a central role in neutrophil activation, and recent studies have demonstrated a strong correlation between IL-17A levels and BD activity. In the present case, elevated serum IL-17A levels and infiltration of IL-17A-positive cells into the renal tissue reflected an active phase of BD and a BD-associated renal lesion. 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 ピア・AI・教員の三者協働フィードバックによるライティング授業の再設計 ―AI利用の実践報告− 174 194 EN Mariko Uzuka Institute for Promotion of Education and Campus Life 10.18926/70120 本稿は、アカデミック・ライティング授業におけるピア・AI・教員のそれぞれの役割と利用順序（自分→ピア→AI→（省察）→教員）を組み込んだ三者協働モデルを設計し、2024〜2025年度に実践した内容を報告する。授業後の学生アンケートでは、AIの即時性・精緻化が評価される一方、依存や有効性の限界に関する懸念も表明された。成績分布においては、AI導入後に下位層が縮小し、学習成果の底上げが示唆された。また、AI誤用や濫用を防ぐには、教室内で建設的な利用法の具体的な指導（例：例文より診断的フィードバックを重視、AI提案の採否理由のメタ記述）が効果的であった。これらの結果から、AIの利点を活かしつつ、学生の判断を中心に据えるライティング授業設計の有効性と課題を提示する。 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.

Wiley Acta Medica Okayama 0022-152X 62 12 2025 An Improved Synthesis of a Key Intermediate for Glycosylation of Biopterin and Its Application for the First Synthesis of Microcystbiopterin B 2021 2029 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Yuta Maeda Department of Chemistry, Faculty of Science, Okayama University Katsuya Iwasaki Department of Chemistry, Faculty of Science, Okayama University A key intermediate for the selective 2′-O-glycosylation of biopterin, N2-(N,N-dimethylaminomethylene)-1′-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]biopterin (12), was efficiently synthesized via a novel route starting from d-glucose, leading to an improved overall yield. This new pathway involves the preparation of a 5-deoxy-l-arabinose phenylhydrazone derivative (9) as a crucial intermediate in the construction of the pteridine ring. Utilizing compound 12, the first synthesis of microcystbiopterin B (4) was accomplished by glycosylation of 12 with 4,6-di-O-acetyl-2-O-(4-methoxybenzyl)-3-O-methyl-α-d-glucopyranosyl bromide (19) in the presence of silver triflate and tetramethylurea, followed by stepwise deprotection. 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.

Wiley Acta Medica Okayama 1085-9489 30 4 2025 A Case of Retinopathy–Sensory Neuropathy Syndrome With a Novel Compound Heterozygous FLVCR1 Variant e70082 EN Yumiko Nakano Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Fukui Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Deguchi Department of Neurology, Okayama City General Medical Center Chika Matsuoka Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohito Kawano Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Taira Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayaka Matsuo Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Osakada Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Taijun Yunoki Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Emi Nomura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mami Takemoto Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuta Morihara Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background and Aims: Retinopathy–sensory neuropathy syndrome (RETSNS), also known as posterior column ataxia with retinitis pigmentosa (PCARP), is a rare neurodegenerative disorder that is caused by biallelic pathogenic variants in FLVCR1. Here, we report a case of a Japanese patient with RETSNS.<br> Methods: Clinical, neuroradiological, and electrophysiological findings were documented. Whole-genome sequencing was performed. Subcloning was carried out to confirm compound heterozygosity. A functional assay was performed to assess the pathogenicity of the variants.<br> Results: The patient showed retinitis pigmentosa and sensory ataxia. Over the course of the disease, autonomic dysfunction has become increasingly evident. Despite consanguinity in the family, whole-genome sequencing identified two heterozygous variants in FLVCR1 (c.369T>G, p.Phe123Leu and c.733A>G, p.Asn245Asp). Cloning of the PCR product followed by Sanger sequencing indicated compound heterozygosity of the variants. Immunocytochemistry of HEK293FT cells transfected with plasmids containing wild-type or variant FLVCR1 cDNA demonstrated altered subcellular localization of the variant FLVCR1 proteins, characterized by reduced membrane localization.<br> Interpretation: We report a novel variant in FLVCR1 causing RETSNS. The functional assay supports the pathogenicity of the variants. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 13 4 2025 Identification of New Repeat Expansion Diseases 244 249 EN Hiroyuki Ishiura Department of Neurology, Okayama UniversityGraduate School of Medicine, Dentistry and Pharmaceutical Sciences Through a genetic study of benign adult familial myoclonus epilepsy (BAFME) type 1, TTTCA and TTTTA repeat expansions have been identified in intron 4 of SAMD12. Lengths of expanded repeats inversely correlated with age at onset of epilepsy. Gain-of-toxic function mechanisms are suggested by the presence of UUUCA-repeat-containing RNA foci. From families with BAFME who did not have repeat expansions in SAMD12, we identified expanded TTTCA and TTTTA repeats in TNRC6A and RAPGEF2. These findings indicated a strong correlation between the repeat motif and the phenotype, leading to the identification of other types of BAFME. We then conducted genetic analysis of neuronal intranuclear inclusion disease (NIID), oculopharyngeal myopathy with leukoencephalopathy (OPML), and oculopharyngodistal myopathy (OPDM). From the observation that NIID, OPML, and OPDM, in addition to fragile X-associated tremor/ataxia syndrome, have shared clinical features, a direct search for CGG repeat expansions successfully led to the identification of the causative genes. Here, I review recent studies on repeat expansions. No potential conflict of interest relevant to this article was reported.

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

Acta Medica Okayama 2025 Trends in childhood obesity in Japan: A nationwide observational study from 2012 to 2021 EN Shintaro FUJIWARA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Impact of Birth Order on Paediatric Allergic Diseases: A National Birth Cohort in Japan EN Mitsuro KOBAYASHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1320-5358 30 5 2025 A Case of IgA Nephropathy With Membranoproliferative Glomerulonephritis-Like Features Miyu Kanazawa, e70057 EN Miyu Kanazawa Okayama University Medical School Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoya Aoki Okayama University Medical School Mihiro Sue Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Miyake Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naruhiko Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Department of Chronic Kidney Disease and Cardiovascular Disease, 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 A 73-year-old man was referred due to the onset of nephrotic-range proteinuria. He had been diagnosed with rheumatoid arthritis 18 years prior and had achieved remission with treatment, including methotrexate and janus kinase (JAK) inhibitor. Although routine follow-ups had not revealed any urinary abnormalities, subsequent tests detected proteinuria and hematuria in the absence of infection or other symptoms. As the urinary abnormalities persisted, with a serum albumin decrease and proteinuria measuring 5.7 g/day, indicating nephrotic syndrome, the patient was referred to our hospital for further evaluation, and a renal biopsy was performed. Light microscopy revealed mesangial cell proliferation, endocapillary proliferation and double-contoured basement membranes. Immunofluorescence microscopy showed IgA-dominant deposits in both mesangial areas and glomerular capillary walls. Transmission electron microscopy demonstrated electron-dense deposits in the mesangium and subendothelial regions, leading to the diagnosis of membranoproliferative glomerulonephritis (MPGN)-type IgA nephropathy. Immunostaining with the Gd-IgA1 (galactose-deficient IgA1)-specific antibody (KM55) was positive, consistent with the diagnosis. Following the initiation of steroid therapy, proteinuria rapidly decreased, achieving complete remission within 5 months. IgA nephropathy with MPGN-like features often presents as nephrotic syndrome, differing from the typical pathological and clinical presentation of IgA nephropathy, making differentiation from secondary MPGN and other diseases sometimes challenging. This case suggests that KM55 staining may offer additional information in differentiating atypical IgA nephropathy with non-classical pathological features. No potential conflict of interest relevant to this article was reported.

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

American Chemical Society (ACS) Acta Medica Okayama 0163-3864 2025 First Total Synthesis of the Kikai Island Polybrominated C3′–N1 Bisindole Alkaloid by a Directed Metalation Strategy EN Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The first total synthesis of one out of four Kikai Island polybrominated C3′–N1 bisindole alkaloids from red alga Laurencia brongniartii is described. The key steps involve both dehydration of trans-hemiaminal and a C2′-methylthiolation of bisindole using dimethyl disulfide through directed metalation, followed by C3-methylthiolation using a N-SMe succinimide reagent. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0385-2407 2025 A Case of Netherton Syndrome/SPINK5-Syndromic Epidermal Differentiation Disorder Evaluated by Serial Tape-Stripping: Persistent Elevation of Serine Protease Activities Despite Clinical Improvement EN Shin Morizane Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Anri Morita Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ko Sunagawa Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hayato Nomura Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken‐Ichi Hasui Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mamoru Ouchida Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1939-5981 2025 Effect of Repeated Gravity Casting on the Microstructure and Mechanical Properties of 6061 Aluminum Alloy EN Mitsuhiro Okayasu Department of Mechanical Systems and Engineering, Okayama University Shouei Makino Department of Mechanical Systems and Engineering, Okayama University Shota Nakagawa Research & Development Center, Marketing & Technology Division, UACJ Corporation Shuhei Takeuchi Department of Mechanical Systems and Engineering, Okayama University Yoshifumi Shinzato Research & Development Center, Marketing & Technology Division, UACJ Corporation Tadashi Minoda Research & Development Center, Marketing & Technology Division, UACJ Corporation Naotaka Ohtsuka Research & Development Center, Marketing & Technology Division, UACJ Corporation This study systematically investigates the effects of repeated gravity casting on the microstructure and mechanical properties of 6061 aluminum alloy. With an increasing number of casting cycles from one to ten, grain coarsening and a decrease in dislocation density were observed, mainly due to the significant depletion of magnesium from 1.03 to 0.01% and titanium from 0.009 to 0.005%. These microstructural changes led to a decrease in solid-solution strengthening and grain-boundary strengthening, resulting in a 30% reduction in tensile strength, while ductility increased by about three times. Moreover, work hardening decreased with increasing the casting cycle, which can be attributed not only to the microstructural changes but also to the increase in stacking fault energy (SFE) associated with compositional evolution. From the transmission electron microscopy (TEM) observations, in the 1-cycle sample, Mg2Si precipitates were finely dispersed and a high amount of Mg element in the matrix, resulting in significant dislocation accumulation, whereas the 10-cycle sample exhibited weaker dislocation tangling. These microstructural evolutions provide insight into the degradation of mechanical performance in aluminum alloys subjected to multiple casting processes. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2510-1560 2025 Enhanced electric power generation in PZT ceramics via stress control EN Mitsuhiro Okayasu Department of Mechanical Systems and Engineering, Okayama University Itsuki Shimazu Department of Mechanical Systems and Engineering, Okayama University This study aimed to enhance the electric power generation of lead zirconate titanate piezoelectric (PZT) ceramics by optimizing stress distribution. Specifically, it focused on applying high stress over a broad area of the PZT ceramic to induce shape deformation in the PZT plate. Pre-straining the PZT plate into an arch shape improved voltage generation, reaching its peak at a maximum deflection of 0.04 mm due to the expanded and intensified stress distribution. However, exceeding this deflection threshold led to a decline in voltage output due to material degradation, including crack formation and 90° domain switching. Finite element analysis confirmed that the increased stress distribution in the pre-strained PZT plate contributed to higher voltage output. Additionally, electron backscatter diffraction analysis revealed that at higher pre-strains (deflection of 0.08 mm), 90°domain switching occurred, resulting in increased internal strain and potential crack formation. Experimental investigations using bulk PZT rods further demonstrated that moderate pre-straining effectively enhanced voltage output. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1939-5981 2025 Upgrading Recycle Technology for Iron Removal in ADC12 Alloy Using Gravity and Magnetic Force EN M. Okayasu Department of Mechanical Systems and Engineering, Okayama University S. Takeuchi Department of Mechanical Systems and Engineering, Okayama University M. Syahid Department of Mechanical Engineering, Hasanuddin University T. Ikeda Department of Mechanical Systems and Engineering, Okayama University As there is a technical issue to remove iron elements during aluminum recycling process, an attempt was made to evaluate the effectiveness of magnetic and gravitational separation methods for removing iron from Al-Si-Cu alloy (ADC12). A rare-earth samarium–cobalt (SmCo) magnet was employed during the solidification process to attract Fe-rich eutectic structures. The microstructural analysis revealed that block-like Fe-Cr-Si-based phases formed preferentially near the magnet and at the bottom of the crucible, suggesting that magnetic and gravity attraction contributed to the localized segregation of these phases. However, other Fe-based phases, including Fe-Si-based ones, are not strongly affected by magnet. Additionally, prolonged heating in the solid–liquid coexistence (SLC) region at 577 °C for 10 h led to the settling of a largely grown Fe-Cr-Si-rich crystal at the bottom of the crucible due to gravity. Other structures, such as Si-rich eutectic phases, were not influenced by gravity, which may be caused by the low density of Si compared to Fe one. From this approach, combining magnetic attraction and gravitational settling is a promising method to promote the removal of iron impurities from aluminum alloys. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0361-5235 54 7 2025 Electric Power Generation of PZT Piezoelectric Ceramics Using Both Direct and Inverse Piezoelectric Effects 5143 5150 EN Mitsuhiro Okayasu Department of Mechanical Systems and Engineering, Okayama University Itsuki Shimazu Department of Mechanical Systems and Engineering, Okayama University The power generation characteristics of lead zirconate titanate (PZT) piezoelectric ceramics (E-PZT) were experimentally investigated using a specialized PZT system which utilizes both the direct and inverse piezoelectric effects inherent to PZT materials. Specifically, electric voltage was generated from the vibration of E-PZT through the inverse piezoelectric effect, induced by mechanical energy transferred from the vibration of a PZT piezoelectric ceramic plate, such as a buzzer (B-PZT). In this system, an insulating material was placed between the B-PZT and E-PZT plates to address the electrical conductivity of the PZT ceramic. Various insulating materials with different thicknesses and different hardness were prepared. Additionally, the PZT systems were mounted in several distinct configurations to evaluate their power generation performance: a fully fixed around the PZT plate and a free-hanging setup. The influence of insulation materials and mounting conditions on electrical output was analyzed at various loading conditions, e.g., loading value and frequency. The results demonstrated that the generated electric voltage decreased with increasing insulation thickness and hardness, suggesting that thinner and softer insulating materials enhance output voltage. Conversely, when the PZT system was securely fixed around the PZT plate with an appropriate fixture, a higher and more stable electric voltage was generated. The voltage generated also varied by the loading condition, which is related to the strain value of the E-PZT plate, demonstrating a linear relationship between the strain and the output voltage. Notably, the strain was significantly influenced by resonant frequencies, which played a crucial role in achieving higher voltage outputs. Based on these experimental results, two power generation systems have been proposed. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0002-7863 2025 Optogenetic Cancer Therapy Using the Light-Driven Outward Proton Pump Rhodopsin Archaerhodopsin-3 (AR3) EN Shin Nakao Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichi Kojima Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keita Sato Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoya Kemmotsu Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hideyo Ohuchi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yosuke Togashi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Sudo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Medicines used for cancer treatment often cause serious side effects by damaging normal cells due to nonspecific diffusion. To address this issue, we previously developed an optical method to induce apoptotic cell death via intracellular pH alkalinization using the outward proton pump rhodopsin, Archaerhodopsin-3 (AR3) in various noncancer model cells in vitro and in vivo. In this study, we applied this method to cancer cells and tumors to evaluate its potential as an anticancer therapeutic strategy. First, we confirmed that AR3-expressing murine cancer cell lines (MC38, B16F10) showed apoptotic cell death upon green light irradiation, as indicated by increased levels of cell death and apoptosis-related markers. Next, we established stable AR3-expressing MC38 and B16F10 cells by using viral vectors. When these AR3-expressing cells were subcutaneously transplanted into C57BL/6 mice, the resulting tumors initially grew at a rate comparable to that of control tumors lacking AR3 expression or light stimulation. However, upon green light irradiation, AR3-expressing tumors exhibited either a marked reduction in size or significantly suppressed growth, accompanied by the induction of apoptosis signals and decreased proliferation signals. These results demonstrate that AR3-mediated cell death has potent antitumor effects both in vitro and in vivo. This optical method thus holds promise as a novel cancer therapy with potentially reduced side effects. 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.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 9 2025 Impact of a Peer-Led International Training Program on Work Motivation Among Early-Career Psychiatrists: A Mixed-Methods Study e93012 EN Toshihiro Shimizu Department of Psychiatry, Saitama Prefectural Psychiatric Hospital Junko Kitaoka Department of Psychiatry, Fukkoukai Tarumi Hospital Ken Suzutani Department of Psychiatry, Aizu Medical Center Yuto Satake Department of Psychiatry, The University of Osaka Masahide Koda Co-learning Community Healthcare Re-innovation Office, Graduate School of Medicine, Okayama University Izumi Kuramochi Department of Epileptology and Psychiatry, National Center of Neurology and Psychiatry Norman Sartorius Psychiatry, Association for the Improvement of Mental Health Programs (AIMHP) Background<br> The Japan Young Psychiatrists Organization (JYPO) has conducted a Course for Academic Development of Psychiatrists (CADP), a peer-led residential international training program, since 2002 to promote the professional development of early-career psychiatrists. This study aimed to evaluate the impact of CADP on participants' work motivation using a psychometric scale and to identify the factors contributing to these changes.<br> Methods<br> We conducted a mixed-method study with 23 Japanese participants of the 21st CADP from March 8 to 10, 2024, in Himeji, Japan. Work motivation was assessed using the abbreviated version of the Measure of Multifaceted Work Motivations (MWM-12) at two time points: two weeks before and three months after the course. The total and subitem scores of the MWM-12 were analyzed using the Wilcoxon signed-rank test. Furthermore, free-text responses collected before and after the course were subjected to qualitative analyses.<br> Results<br> Significant improvements were observed in the MWM-12 total score from pre-course to post-course. Significant increases were also identified in specific sub-items: M1 (directionality of achievement-oriented motivation), M4 (directionality of competition-oriented motivation), M6 (sustainability of competition-oriented motivation), and M9 (sustainability of cooperation-oriented motivation). Qualitative analysis revealed changes in key categories, including growth as a psychiatrist, personal networking, personal growth, and increased motivation. The integration of quantitative and qualitative findings suggested that enhanced career perspectives (M1), professional growth and peer interaction (M4), and increased self-confidence and support networks (M6 and M9) contributed to improved motivation.<br> Conclusion<br> This study demonstrated that a three-day, two-night peer-led training program positively influenced work motivation among early-career psychiatrists. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 2025 Neutrophil-to-lymphocyte ratio affects the impact of proton pump inhibitors on efficacy of immune checkpoint inhibitors in patients with non‑small-cell lung cancer EN Tomoki Hori Department of Pharmacy, Nara Prefecture General Medical Center Kazuhiro Yamamoto Department of Integrated Clinical and Basic Pharmaceutical Science, Okayama University Takefumi Ito Department of Respiratory Medicine, Nara Prefecture General Medical Center Shigeki Ikushima Department of Pharmacy, Nara Prefecture General Medical Center Tomohiro Omura Department of Pharmacy, Kobe University Hospital Ikuko Yano Department of Pharmacy, Kobe University Hospital Background The neutrophil-to-lymphocyte ratio (NLR) at the initiation of immune checkpoint inhibitor (ICI) therapy is a known predictor of prognosis. Proton pump inhibitors (PPIs) reportedly attenuate the therapeutic efficacy of ICIs. However, the attenuation effects are not consistently observed across all patients. This study aimed to evaluate whether NLR serves as a stratification factor to determine the impact of PPI on the efficacy of ICI.<br> Methods This retrospective study was conducted in patients with NSCLC treated with ICI monotherapy. Patients were stratified into two groups (higher NLR (≥ 4) and lower NLR (< 4)). PPI use was defined as the administration of PPIs within 30 days before or after ICI initiation. The primary outcome was progression-free survival (PFS) and the secondary outcome was overall survival (OS).<br> Results Among the 132 patients included, PPI users exhibited significantly shorter median PFS and OS than non-PPI users. In the higher NLR group (n = 61), PPI users had a markedly shorter PFS and OS than non-PPI users (median PFS: 1.6 vs. 8.2 months; p < 0.01, median OS: 3.3 vs. 19.6 months; p = 0.015). Conversely, in the lower NLR group (n = 71), no significant difference in PFS and OS was observed between PPI users and non-PPI users (median PFS: 2.8 vs. 7.3 months, p = 0.83, median OS: 17.6 vs. 24.4 months, p = 0.40).<br> Conclusion NLR may be a significant stratification factor for evaluating the impact of PPI on PFS and OS in patients with NSCLC undergoing ICI monotherapy. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1598-2351 2025 Hydrogen Embrittlement Characteristics of Austenitic Stainless Steels After Punching Process EN Mitsuhiro Okayasu Department of Mechanical and Systems Engineering, Okayama University Xichang Li Department of Mechanical and Systems Engineering, Okayama University Tomohisa Kawakami SHOYO SANGYO Co., Ltd. This study investigates the influence of microstructural characteristics on the hydrogen embrittlement of SUS304 austenitic stainless steel. The investigation utilized SUS304 sheets with a thickness of 1.5 mm, which were processed by punching with an 8 mm diameter to make specimens. Severe plastic deformation was localized near the punching edge, with the extent of deformation determined by the punching speed. Slower punching speeds induced more pronounced plastic strain, which was closely associated with work hardening and strain-induced martensitic (SIM) transformation. The SIM phase was predominantly observed within a depth of approximately 0.1 mm from the punched edge when processed at a punching speed of 0.25 mm/s, corresponding to roughly 10% of the cross-sectional area of the sample. These microstructural changes led to a significant reduction in tensile and fatigue strength, thereby exacerbating susceptibility to severe hydrogen embrittlement, despite the limited extent of microstructural alteration. Based on these findings, a modified Goodman diagram for SUS304 austenitic stainless steel, incorporating mechanical properties and hydrogen embrittlement behavior, was proposed. No potential conflict of interest relevant to this article was reported.

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

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

Oxford University Press (OUP) Acta Medica Okayama 0002-9262 2025 Immortal time bias from selection: a principal stratification perspective kwaf146 EN Bronner P Gonçalves Faculty of Health and Medical Sciences, University of Surrey Etsuji Suzuki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Immortal time bias due to post-treatment definition of eligibility criteria can affect experimental and observational studies, and yet, in contrast to the extensive literature on the classical form of immortal time bias, it has seldom been the focus of methodological discussions. Here, we propose an account of eligibility-related immortal time bias that uses the principal stratification framework to explain the noncomparability of treatment arms (or exposure groups) conditional on selection. In particular, we show that the statistical estimand that conditions on observed eligibility after time zero of follow-up can be interpreted using partially overlapping principal strata. Furthermore, we show that, under this perspective, as the timing of eligibility approaches time zero of follow-up, the probabilities of the outcome for eligible individuals monotonically approach the corresponding unconditional (in absence of selection) expected potential outcomes under different treatment levels. Our study provides a potential outcomes-based explanation of eligibility-related immortal time bias, and indicates that, in addition to the target trial emulation framework, principal effects might, for some studies, be useful causal estimands. 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.

Elsevier BV Acta Medica Okayama 0960-9822 35 12 2025 Oxytocin facilitates human touch-induced play behavior in rats 2916 2926.e3 EN Himeka Hayashi Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University, Sayaka Tateishi Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University Ayumu Inutsuka Division of Brain and Neurophysiology, Department of Physiology, Jichi Medical University Sho Maejima Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University Daisuke Hagiwara Department of Neuropeptide Research in Psychiatry, Central Institute of Mental Health, German Center for Psychiatry (DZPG), Medical Faculty Mannheim, University of Heidelberg Yasuo Sakuma Department of Anatomy and Neurobiology, Graduate School of Medical Sciences, Nippon Medical School Tatsushi Onaka Division of Brain and Neurophysiology, Department of Physiology, Jichi Medical University Valery Grinevich Department of Neuropeptide Research in Psychiatry, Central Institute of Mental Health, German Center for Psychiatry (DZPG), Medical Faculty Mannheim, University of Heidelberg Hirotaka Sakamoto Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University, Pleasant touch sensations play a fundamental role in social bonding, yet the neural mechanisms underlying affinity-like behaviors remain poorly understood. Here, we demonstrate that juvenile-adolescent rats, which naturally engage in social play with peers characterized by rough-and-tumble interactions and 50 kHz ultrasonic vocalizations indicating pleasant sensations, develop a strong affinity for human hands through similar playful contact achieved by repeated tickling with human hands. Using this rat with tickling-induced high affinity for human hands, we discovered that repeated tickling mimicking rough-and-tumble play led to increased oxytocin receptor (OTR) expression in the ventrolateral part of the ventromedial hypothalamus (VMHvl). Inhibition of oxytocin signaling in the VMHvl reduced affinity-like behaviors from rats to human hands. These findings suggest that OTR neurons in VMHvl play an important role in the increase in affinity for human hands induced by pleasant touch sensation with human touch-induced play behavior. Based on retrograde and anterograde tracing studies examining the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) as primary sources of oxytocin, we demonstrate that a subset of oxytocin fibers in the VMHvl originate from the SON, suggesting that affinity-like behavior from rats to human hands may be controlled by oxytocin signaling from magnocellular neurons. Together, this work advances our understanding of how oxytocin shapes social behavior and may inform the development of therapeutic strategies to promote positive social interactions. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1441-0745 27 3 2025 Factors Influencing Pain Management Practices Among Nurses in University Hospitals in Western Japan: A Cross‐Sectional Study Using Hierarchical Multiple Regression Analysis e70143 EN Mengyao Xi Doctor's Program, Graduate School of Health Sciences, Okayama University Yuki Kajiwara Faculty of Health Sciences, Okayama University Michiko Morimoto Faculty of Health Sciences, Okayama University Effective pain management remains a global nursing challenge, requiring awareness of influencing factors. This cross-sectional study examined such factors among nurses in Western Japan's university hospitals from September to November 2023. A self-reported questionnaire was used to investigate nurses' sociodemographic characteristics, collaboration with physicians in the ward, pain management knowledge, empathy, and pain management practices. Among 695 nurses (69.4% valid response rate), 51.4% had under 5 years' work experience, indicating a relatively junior nursing workforce. The mean practice score was 47.5 (SD = 7.1). Hierarchical regression showed knowledge and empathy increased practice scores by 6.2%. Nurses' empathy, particularly their perspective-taking, explained pain management practice (β = 0.242, p < 0.001). Information-sharing with pain specialists, effective collaboration with physicians in the ward, work experience, and clinical pain education were also associated with pain management practices (all p < 0.05). This study suggests that enhancing nurses' empathy and fostering a collaborative ward environment may be essential strategies to improve the pain management quality. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0743-7463 41 21 2025 Unraveling the Molecular Mechanism of Transient Multilamellar Formation in Ethanol-Modified Vesicle Solutions 13372 13380 EN Kana Shibata Department of Materials Chemistry, Nagoya University Masatoshi Maeki Division of Applied Chemistry, Faculty of Engineering, Hokkaido University Manabu Tokeshi Division of Applied Chemistry, Faculty of Engineering, Hokkaido University Wataru Shinoda Research Institute for Interdisciplinary Science, Okayama University A recent microfluidic-based small-angle X-ray scattering (SAXS) measurement intriguingly suggested the transient formation of multilamellar structures during the mixing of unilamellar vesicles with ethanol in an aqueous solution. This study explores a possible molecular mechanism underlying this phenomenon, primarily through coarse-grained molecular dynamics (CG-MD) simulations. We first examined lipid aggregate morphology as a function of ethanol concentration in an aqueous solution. Even though vesicles were observed in pure aqueous solution, increasing ethanol concentrations led to more frequent pore formation in vesicular membranes. At ethanol concentrations above 52%, vesicles destabilized and transformed into worm-like micelles. We hypothesized that the transient multilamellar structures might arise from vesicle stacking due to variations in the effective interactions between vesicles. However, a series of potential of mean force (PMF) calculations consistently showed repulsive interactions between vesicles, regardless of ethanol concentration, ruling out this possibility. In contrast, once lipid aggregates transformed into worm-like micelles, the PMF barrier between them dropped (∼5kBT), promoting fusion. Our CG-MD simulations further demonstrated that lipid aggregates (micelles) readily fused and grew in high ethanol concentrations. Upon subsequent exposure to lower ethanol levels, these enlarged aggregates reorganized into vesicles with internal lamellar structure─multilamellar vesicles. These findings suggest that the heterogeneous mixing of unilamellar vesicular solutions with ethanol in a microfluidic device plays a key role in the emergence of transient multilamellar structures. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1523-7060 2025 Transformation of α,β-Unsaturated Aldehydes with a Small Amount of Electricity: Cyanosilylation, Isomerization, and Nucleophilic Addition EN Mayu Fujii Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nanaho Ueno Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koichi Mitsudo Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Eisuke Sato Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Seiji Suga Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University An electrochemical method was developed to convert α,β-unsaturated aldehydes into carboxylic acid derivatives via cyanosilylation, isomerization, and nucleophilic addition. This reaction is more sustainable than the usual electrochemical organic reaction because this reaction proceeds catalytically with active species generated by a very small amount of electricity. Furthermore, scale-up synthesis with a flow reactor has been achieved. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Low frequency of intracranial progression in advanced NSCLC patients treated with cancer immunotherapies EN Naoya KEMMOTSU Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Baseline gut microbiota as a predictive marker for the efficacy of neoadjuvant chemotherapy in patients with early breast cancer: a multicenter prospective cohort study in the Setouchi Breast Project‑14 EN Shogo NAKAMOTO Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2193-5807 2025 2-Hydroxy-3-(Pyrrolidin-1-yl)-Indolines: A Platform for Accessing Decorated Deaminokynurenines Enabled by a Double Tautomeric Control e202500439 EN Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University In this study we introduce indoline hemiaminals as phenacyl bromide surrogates for the synthesis of deaminokynurenine derivatives through cyclic-linear tautomeric intermediates. The reaction proceeds through a tandem process involving the ring opening of indoline hemiaminals, generating transient acyclic aldehydes which are then trapped with in situ generated enolate species. Our protocol overcomes traditional dilemma in production of polar-mismatch 1,4-dicarbonyl compounds by utilizing a transient highly electrophilic linear aldehyde and late-stage transposition of carbonyl moiety. The synthetic utility of our transformation was demonstrated by follow-up transformations, including the first total synthesis of quinoline-2,4-dione alkaloid. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0306-5251 2025 Comprehensive analysis of adverse event profile changes with pertuzumab addition to trastuzumab‐based breast cancer therapy: Disproportionality analysis using VigiBase EN Tatsuaki Takeda Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Jun Matsumoto Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Tomonori Sakai Department of Pharmacy, Okayama University Hospital Naohiro Iwata Department of Pharmacy, Okayama University Hospital Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Noritaka Ariyoshi Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Aims: Pertuzumab is used in combination with trastuzumab-based therapy for HER2-positive breast cancer. However, real-world safety information on pertuzumab remains limited. This study assessed the safety of adding pertuzumab to trastuzumab-based therapy for HER2-positive breast cancer using real-world data.<br> Methods: VigiBase, the World Health Organization's global database of adverse events (AEs), containing reports from November 1967 to December 2023, was used. Signals for pertuzumab-associated AEs in breast cancer cases were detected using the reporting odds ratio (ROR).<br> Results: Signals of trastuzumab plus pertuzumab relative to trastuzumab alone were detected in gastrointestinal disorders (ROR: 1.45, 95% confidence interval: 1.26–1.67), including diarrhoea (3.49, 2.83–4.30); infections and infestations (1.54, 1.24–1.91); and skin and subcutaneous tissue disorders (ROR: 1.63, 1.40–1.90), including pruritus (1.96, 1.51–2.55) and rash (1.63, 1.20–2.23). Further, signals of trastuzumab plus docetaxel plus pertuzumab relative to those of trastuzumab plus docetaxel were detected in gastrointestinal disorders (1.63, 1.38–1.93), including nausea (1.72, 1.24–2.39) and vomiting (1.48, 1.01–2.17), and in nervous system disorders (1.50, 1.20–1.87), including paraesthesia (2.60, 1.33–5.08) and peripheral sensory neuropathy (5.94, 1.79–19.71). The frequency of AEs causing or prolonging hospitalization was increased with trastuzumab plus pertuzumab compared to that with trastuzumab alone (1.18, 1.00–1.38).<br> Conclusions: AE profiles after the addition of pertuzumab to trastuzumab-based therapy were comprehensively identified. The findings in this study highlight the importance of considering these AEs when selecting pertuzumab combination therapy to ensure the safety of patients with breast cancer. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1523-7060 27 18 2025 Electrochemical Oxidation of Benzyl Alcohols via Hydrogen Atom Transfer Mediated by 2,2,2-Trifluoroethanol 4737 4741 EN Takahiro Kawajiri API R&D Laboratory, Research Division, Shionogi & Co., Ltd. Masahiro Hosoya API R&D Laboratory, Research Division, Shionogi & Co., Ltd. Satoshi Goda API R&D Laboratory, Research Division, Shionogi & Co., Ltd. Eisuke Sato Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Seiji Suga Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University We report a novel electrochemical oxidation of benzyl alcohols. We found that trifluoroethanol plays a role as a hydrogen atom transfer (HAT) mediator, enabling the oxidation of electron-deficient substrates that are difficult to directly oxidize on electrode surfaces. Density functional theory calculations, cyclic voltammetry measurements, and constant potential electrolysis studies supported the proposed HAT mechanism. Moreover, the obtained carbonyl compounds could be functionalized in an electrochemical one-pot manner, further highlighting their synthetic utility. No potential conflict of interest relevant to this article was reported.

岡山大学教師教育開発センター Acta Medica Okayama 2186-1323 15 2025 児童の自己理解を促すキャリア教育の実践事例の検討　―強み介入を活用して― 267 279 EN Shinji YOSHIKAWA Uwanari Elementary School Kouhei ISODA Uwanari Elementary School Tsuguyuki IZUMI Faculty of Education, Okayama University 10.18926/CTED/68496 本研究では，公立小学校4年生を対象に，キャリア教育における自己理解能力の育成を目的とし，ポジティブ心理学に基づく性格特性的強み介入 (Character Strengths Intervention：CSI) と将来の夢についての学習を関連付けた学級活動 (３) の授業を行った。本実践を通して，児童は自分の強みを理解し，それを将来に活かそうとする意識が高まるとともに，互いの強みを認め合う活動によって児童同士の関係性の構築が促進された。一方で，学校全体でのキャリア教育の系統性と発展性の検討，強みの活用が難しい児童への個別支援の必要性が今後の課題として指摘された。 No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0743-7463 41 11 2025 Droplet Impact Behavior on Convex Surfaces with a Circumferential Wettability Difference 7640 7647 EN Taku Ishikawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yutaka Yamada Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kazuma Isobe Faculty of Environmental, Life, Natural Science and Technology, Okayama University Akihiko Horibe Faculty of Environmental, Life, Natural Science and Technology, Okayama University Controlling the bouncing behavior of the impacting droplets is an important issue for splay cooling, icing prevention, and other applications. The bouncing behavior of impacting droplets on superhydrophobic curved surfaces and flat substrates with a wettability difference has been widely investigated, and droplets impacting these surfaces show shorter contact times than those on superhydrophobic flat surfaces and droplet transport. However, there have been few studies on the droplet impact behavior on curved surfaces with a wettability difference, where efficient droplet control could be achieved by combining the features. In the present study, droplet impact experiments were conducted using copper cylinders with different circumferential wettabilities from hydrophilic to superhydrophobic, varying the impact velocity, cylinder diameter, and rotation angle. Droplets that impacted the wettability boundary showed asymmetric deformation and moved to the hydrophilic side, owing to the driving force of the wettability difference. Moreover, the droplet behavior was classified into four types: the droplet bounced off the surface, the droplet bounced off the surface and split, the droplet attached to the surface, and the droplet attached to the surface and split. The droplet behavior was estimated by using the maximum spreading width of the droplet impacted on the flat substrate. We evaluated whether the droplets attached to the surface or bounced off the surface after impact using the Weber number and rotation angle, and the estimations were in agreement with the experimental results for cylinder diameters of 4 and 6 mm. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 14 4 2025 Natural Course and Long-Term Outcomes of Gastric Subepithelial Lesions: A Systematic Review 1055 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Objectives: Gastric subepithelial lesions (SELs) are often incidentally detected during endoscopic examinations, with most patients being asymptomatic and lesions measuring <20 mm. Despite their generally indolent nature, certain SELs, such as gastrointestinal stromal tumors, require resection. Current guidelines recommend periodic surveillance; however, the natural course and long-term outcomes of gastric SELs have not been sufficiently investigated. This systematic review aimed to synthesize evidence on the progression, growth rate, and risk factors associated with gastric SELs to inform clinical management strategies. Methods: A comprehensive search of PubMed was conducted for peer-reviewed studies published between January 2000 and November 2024. Eligible studies included original studies on the follow-up and progression of gastric SELs. Non-English articles, reviews, case reports, and unrelated topics were excluded. In total, 277 articles were screened, with 15 additional articles identified through manual screening. Ultimately, 41 articles were included in the analysis. The study protocol is registered in PROSPERO (CRD42024614865). Results: Large-scale studies reported low growth rates of 2.0-8.5% over 2.0-5.0 years, while smaller studies reported a broader range of growth rates of 5.4-28.4%. The factors contributing to these discrepancies include patient selection, follow-up duration, and growth criteria. Risk factors for lesion size increase include larger initial lesion size, irregular margins, heterogeneous echo patterns, and certain tumor locations. Conclusions: These findings underscore the need for individualized management strategies based on lesion size, imaging characteristics, and risk factors. The close monitoring of high-risk lesions is crucial for timely intervention. Standardized growth criteria and optimized follow-up protocols are essential for improving clinical decision making and patient outcomes. No potential conflict of interest relevant to this article was reported.

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

Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 64 2 2024 Atypical lymphoplasmacytic and immunoblastic proliferation: A Systematic Review 97 106 EN Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Toshiaki Takahashi Department of Medicine, John A. Burns School of Medicine, University of Hawai’i Kensuke Takaoka Department of Medicine, John A. Burns School of Medicine, University of Hawai’i Sharina Macapagal Department of Medicine, John A. Burns School of Medicine, University of Hawai’i Chalothorn Wannaphut Department of Medicine, John A. Burns School of Medicine, University of Hawai’i Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Hiroko Toda Department of Pathology, Chugoku Central Hospital Yoshito Nishimura Department of Medicine, John A. Burns School of Medicine, University of Hawai’i Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) was first reported in 1984 as characteristic histological findings in lymph nodes associated with autoimmune diseases, but it has not been clearly defined to date. To summarize the histological characteristics and clinical diagnoses associated with ALPIBP, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including “atypical lymphoplasmacytic and immunoblastic lymphadenopathy” from their inception to December 27, 2023. We also summarized the courses of three cases with a pathological diagnosis of ALPIBP. Nine articles with 52 cases were included. Among the total of 55 cases, including the three from our institution, the median age of the cases was 63.5 years with a female predominance (69.5%). Lymphadenopathy was generalized in 65.6% and regional in 34.4% of cases. RA (24.4%), SLE (24.4%), and autoimmune hemolytic anemia (20.0%), were common clinical diagnoses. A combination of cytotoxic chemotherapy was used in 15.6% of cases due to the suspicion of malignancy. Nodal T-follicular helper cell lymphoma, angioimmunoblastic type, methotrexate-associated lymphoproliferative disorders, and IgG4-related diseases were listed as important diseases that need to be pathologically differentiated from ALPIBP. This review summarizes the current understanding of the characteristics of ALPIBP. Given that underrecognition of ALPIBP could lead to overdiagnosis of hematological malignancy and unnecessary treatment, increased awareness of the condition in pathologists and clinicians is crucial. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1520-6106 129 2 2024 Hydronium Ions Are Less Excluded from Hydrophobic Polymer–Water Interfaces than Hydroxide Ions 726 735 EN Ryan L. Myers Department of Chemistry, The Pennsylvania State University, University Park Aoi Taira Department of Chemistry, Okayama University Chuanyu Yan Department of Chemistry, The Pennsylvania State University, University Park Seung-Yi Lee Department of Chemistry, The Pennsylvania State University, University Park Lauren K. Welsh Department of Chemistry, The Pennsylvania State University, University Park Patrick R. Ianiro Department of Chemistry, University of Pittsburgh at Bradford Tinglu Yang Department of Chemistry, The Pennsylvania State University, University Park Kenichiro Koga Department of Chemistry, Okayama University Paul S. Cremer Department of Chemistry, The Pennsylvania State University, University Park The cloud point temperatures of aqueous poly(N-isopropylacrylamide) (PNIPAM) and poly(ethylene) oxide (PEO) solutions were measured from pH 1.0 to pH 13.0 at a constant ionic strength of 100 mM. This ionic strength was reached by mixing the appropriate concentration of NaCl with either HCl or NaOH. The phase transition temperature of both polymers was nearly constant between pH 2.0 and 12.0. However, the introduction of 100 mM HCl (pH 1.0) led to an increase in the cloud point temperature, although this value was still lower than the cloud point temperature in the absence of salt. By contrast, the introduction of 100 mM NaOH (pH 13.0) caused a decrease in the cloud point temperature, both relative to adding 100 mM NaCl and adding no salt. Nuclear magnetic resonance (NMR) studies of these systems were performed below the cloud point temperature, and the chemical shifts closely tracked the corresponding changes in the phase transition temperature. Specifically, the introduction of 100 mM HCl caused the 1H chemical shift to move downfield for the CH resonances from both PNIPAM and PEO, while 100 mM NaOH caused the same resonances to move upfield. Virtually no change in the chemical shift was seen between pH 2.0 and 12.0. These results are consistent with the idea that a sufficient concentration of H3O+ led to polymer swelling compared to Na+, while substituting Cl– with OH– reduced swelling. Finally, classical all-atom molecular dynamics (MD) simulations were performed with a monomer and 5-mer corresponding to PNIPAM. The results correlated closely with the thermodynamic and spectroscopic data. The simulation showed that H3O+ ions more readily accumulated around the amide oxygen moiety on PNIPAM compared with Na+. On the other hand, OH– was more excluded from the polymer surface than Cl–. Taken together, the thermodynamic, spectroscopic, and MD simulation data revealed that H3O+ was less depleted from hydrophobic polymer/water interfaces than any of the monovalent Hofmeister metal cations or even Ca2+ and Mg2+. As such, it should be placed on the far-right side of the cationic Hofmeister series. On the other hand, OH– was excluded from the interface and could be positioned in the anionic Hofmeister series between H2PO4– and SO42–. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 13 3 2025 Long-Term Follow-Up of a Patient With SPG11 198 200 EN Yosuke Osakada Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chika Matsuoka Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Fukui Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichiro Tsunoda Department of Neurology, Tsuyama Chuo Hospital Kentaro Deguchi Department of Neurology, Okayama City Hospital Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Ishiura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University We present a case of a male patient with disease-causing variants in SPG11, a causative gene for autosomal recessive spastic paraplegia with a thin corpus callosum (ARHSP-TCC), as well as juvenile amyotrophic lateral sclerosis (ALS5) and Charcot–Marie–Tooth disease (CMT2X). A neurological examination at age 18 revealed dysarthria, muscle weakness in bilateral lower extremities, hyperreflexia in patellar reflex, hyporeflexia in Achilles reflex with an extensor plantar reflex, and intellectual disability. Magnetic resonance imaging revealed a thin corpus callosum and ears of the lynx sign. At the age of 26, weakness and muscle atrophy progressed. While no sensory disturbances were noted, there was a mild decrease in sensory nerve action potentials of the sural nerve over the 8 years between 18 and 26. Clinicians should be aware that SPG11 belongs to the same spectrum of disorders as ALS5 and CMT2X and presents various phenotypes depending on the stage of the disease. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1751-0759 18 1 2024 Psychogenic fever and neurodevelopmental disorders among Japanese children 23 EN Ayumi Okada Department of Pediatrics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshie Shigeyasu Department of Pediatrics, Okayama University Hospital Chikako Fujii Department of Pediatrics, Okayama University Hospital Chie Tanaka Department of Pediatrics, Okayama University Hospital Mana Hanzawa Department of Pediatrics, Okayama University Hospital Akiko Sugihara Department of Pediatrics, Okayama University Hospital Makiko Horiuchi Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Psychosocial stress can induce various physical symptoms, including fever, which is a commonly seen symptom in pediatric practice. In cases of unexplained fever, psychogenic fever should be considered as a potential cause. Children with neurodevelopmental disorders may be more vulnerable to stress and therefore more prone to developing somatic symptoms than their peers. This study aimed to elucidate the characteristics of children with psychogenic fever and comorbidity.<br> Methods This study included 21 patients with psychogenic fever who visited the Department of Pediatric Psychosomatic Medicine, Okayama University Hospital. Information on age, sex, disease onset, final estimated diagnosis, comorbidities, treatment course, and outcome was obtained from the patients' medical records.<br> Results Of the 21 patients included, 7 were boys and 14 were girls, and their median age was 13.0 (range: 8.6-14.6) years. A total of 19 patients had no attendance at school, and all patients showed signs of maladjustment in school. The comorbidities included orthostatic dysregulation (n = 4) and migraine (n = 3). Neurodevelopmental disorders were observed in nine patients, eight of whom were diagnosed after the initial visit. The mean treatment duration was 37.2 months. The outcomes were complete remission (n = 9), improvement (n = 4), discontinuation (n = 1), and referral to another physician (n = 7).<br> Conclusion Various comorbidities were observed in the patients of this study with psychogenic fever, including the coexistence of neurodevelopmental disorders, such as autistic spectrum disorder. Children with neurodevelopmental disorders are prone to psychological stress resulting from difficulties in social adjustment. It is crucial to understand the developmental characteristics and environmental adaptation of patients to facilitate accurate diagnosis and treatment. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0947-6539 31 14 2025 Graphene Oxide as a Self‐Carbocatalyst to Facilitate the Ring‐Opening Polymerization of Glycidol for Efficient Polyglycerol Grafting e202404400 EN Yajuan Zou Research Institute for Interdisciplinary Science, Okayama University Kentaro Ohkura Graduate School of Natural Science and Technology, Okayama University Israel Ortiz‐Anaya Research Institute for Interdisciplinary Science, Okayama University Ryota Kimura Graduate School of Natural Science and Technology, Okayama University Alberto Bianco Research Institute for Interdisciplinary Science, Okayama University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Grafting carbon-based nanomaterials (CNMs) with polyglycerol (PG) improves their application potentials in biomedicine and electronics. Although “grafting from” method offers advantages over “grafting to” one in terms of operability and versatility, little is known about the reaction process of glycidol with the surface groups onto CNMs. By using graphene oxide (GO) as a multi-functional model material, we examined the reactivity of the surface groups on GO toward glycidol molecules via a set of model reactions. We reveal that carboxyl groups spontaneously react with the epoxide ring with no need of catalyst, while GO catalyzes the reactions of hydroxyl groups with the epoxide of glycidol. In addition, the hydroxyl group of glycidol can open the epoxide in the basal plane of GO. The subsequent polymerization of PG is supposed to propagate at the primary and/or the secondary hydroxyl groups, generating a ramified PG macromolecule with random branch-on-branch topology. In addition, ketones, benzyl esters and aromatic ethers are found not to react with glycidol even in the presence of GO, while the aldehydes are easily oxidized into carboxyl groups under ambient condition, behaving then as the carboxyl groups. Our findings pose the foundation for understanding the polymerization mechanism of PG on CNMs. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 2193-5807 14 2 2024 Potassium tert-Butoxide-Mediated Ring-Opening of Indolines: Concise Synthesis of 2-Vinylanilines e202400552 EN Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shota Asai School of Pharmacy, Shujitsu University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University A concise and metal-free procedure has been developed for the synthesis of 2-vinylanilines. Reactions of indolines with tert-BuOK in DMSO afford the decorated 2-vinylanilines in yields up to 92 %. In addition, the 2, or 3-substituted indolines could be converted to trisubstituted alkenes. Also, the protocol can be scaled to afford gram quantities of the decorated 2-vinylanilines. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 The concept of X-Ray CT dose evaluation method using radiochromic film and film-folding phantom EN Nobuyoshi TANKI Graduate School of Health Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Delayed diagnostic interval and survival outcomes in pediatric leukemia: A single-center, retrospective study EN Kosuke TAMEFUSA 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 Trans men can achieve adequate muscular development through low-dose testosterone therapy: A long-term study on body composition changes EN Yusuke TOMINAGA 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 Radiological characteristics of skeletal growth in neonates and infants with achondroplasia EN Daisuke MIYAHARA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0366-7022 53 11 2024 SNAr hexafluoroisopropoxylation of electron-rich aryl fluoride with a catalytic electrical input upae196 EN Eisuke Sato Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tomohiro Nakahama Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koichi Mitsudo Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Seiji Suga Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Anodic oxidation–promoted SNAr reactions of electron-rich aryl fluoride were developed. The anodic oxidation of 4-fluoroanisole in hexafluoroisopropyl alcohol (HFIP) with K2CO3 led to SNAr-type hexafluoroisopropoxylation, and the reaction was completed with a catalytic electrical input. The results of cyclic voltammetry suggest that the radical cation of 4-fluoroanisole, which would react with the alkoxide of HFIP, is generated. Electron transfer between the intermediate and the starting material constructs the catalytic cycle, and the elimination of fluoride from the Meisenheimer complex produces the desired compound. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1865-0333 18 1 2024 Deep learning-based approach for acquisition time reduction in ventilation SPECT in patients after lung transplantation 47 57 EN Masahiro Nakashima Division of Radiological Technology, Okayama University Hospital Ryohei Fukui Department of Radiological Technology, Faculty of Health Sciences, Okayama University Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University We aimed to evaluate the image quality and diagnostic performance of chronic lung allograft dysfunction (CLAD) with lung ventilation single-photon emission computed tomography (SPECT) images acquired briefly using a convolutional neural network (CNN) in patients after lung transplantation and to explore the feasibility of short acquisition times. We retrospectively identified 93 consecutive lung-transplant recipients who underwent ventilation SPECT/computed tomography (CT). We employed a CNN to distinguish the images acquired in full time from those acquired in a short time. The image quality was evaluated using the structural similarity index (SSIM) loss and normalized mean square error (NMSE). The correlation between functional volume/morphological volume (F/M) ratios of full-time SPECT images and predicted SPECT images was evaluated. Differences in the F/M ratio were evaluated using Bland–Altman plots, and the diagnostic performance was compared using the area under the curve (AUC). The learning curve, obtained using MSE, converged within 100 epochs. The NMSE was significantly lower (P < 0.001) and the SSIM was significantly higher (P < 0.001) for the CNN-predicted SPECT images compared to the short-time SPECT images. The F/M ratio of full-time SPECT images and predicted SPECT images showed a significant correlation (r = 0.955, P < 0.0001). The Bland–Altman plot revealed a bias of -7.90% in the F/M ratio. The AUC values were 0.942 for full-time SPECT images, 0.934 for predicted SPECT images and 0.872 for short-time SPECT images. Our findings suggest that a deep-learning-based approach can significantly curtail the acquisition time of ventilation SPECT, while preserving the image quality and diagnostic accuracy for CLAD. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0002-9262 193 11 2024 Re: “Defining and identifying local average treatment effects” 1641 1642 EN Etsuji Suzuki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eiji Yamamoto Okayama University of Science No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0271-3586 67 11 2024 Job strain and adverse pregnancy outcomes: A scoping review and meta‐analysis 971 979 EN Kota Nakayama Okayama University Medical School Etsuji Suzuki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Natalie Slopen Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health Ichiro Kawachi Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health Background: Previous studies have shown that job strain is associated with low birthweight (LBW), preterm birth (PTB), and small for gestational age (SGA). We conducted a scoping review and meta-analysis to assess the association between job strain and adverse pregnancy outcomes.<br> Methods: A literature search was performed on PubMed. We included English-language studies that examined the association between job strain (based on the Karasek demand-control model) and pregnancy outcomes. We excluded letters, posters, reviews, and qualitative studies. Random effects meta-analysis was performed. Heterogeneity was assessed using τ2 and I2 statistics. Potential bias was assessed using standard funnel plots. Asymmetry was evaluated by Egger's test. Leave-one-out analysis was performed for sensitivity analyses.<br> Results: Three eligible studies were found for LBW, seven for PTB, and four for SGA. The number of subjects ranged from 135 to 4889, and the prevalence of high job strain ranged from 6.64% to 33.9%. The pooled odds ratio and 95% confidence interval (CI) for LBW, PTB, and SGA were 1.23 (95% CI: 0.97, 1.56), 1.10 (95% CI: 1.00, 1.22), and 1.16 (95% CI: 0.97, 1.39) respectively, indicating modest associations. Heterogeneity for LBW and PTB may not be important but may be moderate for SGA. No publication bias was detected for LBW and PTB, but possible publication bias exists for SGA.<br> Conclusion: We found a modest association between job strain and PTB. Since job strain is only one of the many aspects of an unhealthy work environment, interventions that improve working conditions more broadly are needed. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2212-5345 62 5 2024 A randomized, open-label phase II study on the preventive effect of goshajinkigan against peripheral neuropathy induced by paclitaxel-containing chemotherapy: The OLCSG2101 study protocol 897 900 EN Naoki Nakamura Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Go Makimoto Department of Allergy and Respiratory Medicine, Okayama University Hospital Takaaki Tanaka Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuka Kato Center of Innovative Clinical Medicine, Okayama University Hospital Isao Oze Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute Toshiyuki Kozuki Department of Respiratory Medicine, Shikoku Cancer Center Toshihide Yokoyama Department of Respiratory Medicine, Kurashiki Central Hospital Hirohisa Ichikawa Department of Respiratory Medicine, KKR Takamatsu Hospital Shoichi Kuyama Department of Respiratory Medicine, Iwakuni Clinical Center Naofumi Hara Department of Respiratory Medicine, Okayama Rosai Hospital Yoshinobu Maeda Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Hotta Center of Innovative Clinical Medicine, Okayama University Hospital Background: Paclitaxel (PTX) is an essential cytotoxic anticancer agent and a standard treatment regimen component for various malignant tumors, including advanced unresectable non-small cell lung cancer, thymic cancer, and primary unknown cancers. However, chemotherapy-induced peripheral neuropathy (CIPN) caused by PTX is a significant adverse event that may lead to chemotherapy discontinuation and deterioration of the quality of life (QOL). Although treatment modalities such as goshajinkigan (GJG), pregabalin, and duloxetine are empirically utilized for CIPN, there is no established evidence for an agent as a preventive measure. We designed a randomized phase II trial (OLCSG2101) to investigate whether prophylactic GJG administration can prevent the onset of CIPN induced by PTX.<br> Methods: This study was designed as a two-arm, prospective, randomized, multicenter phase II trial. The patients will be randomly assigned to either the GJG prophylaxis arm (Arm A) or the GJG non-prophylaxis arm (Arm B), using cancer type (lung cancer or not) and age (<70 years or not) as adjustment factors. A total of 66 patients (33 in each arm) will be enrolled.<br> Discussion: The results of this study may contribute to better management of CIPN, which can enable the continuation of chemotherapy and maintenance of the patient's QOL.<br> Ethics and dissemination: Ethical approval was obtained from the certified review board of Okayama University (approval no. CRB21-005) on September 28, 2021. Results will be published in peer-reviewed journals and presented at national and international conferences.<br> Trial registration: Japan Registry of Clinical Trials (registration number jRCTs061210047). No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1860-8965 38 2 2020 The neurotoxicity of psychoactive phenethylamines “2C series” in cultured monoaminergic neuronal cell lines 394 408 EN Masato Asanuma Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ikuko Miyazaki Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiko Funada Division of Drug Dependence, National Institute of Mental Health, National Center of Neurology and Psychiatry Purpose The aim of this study was to evaluate the neurotoxicity of psychoactive abused 2,5-dimethoxy-substituted phenethylamines “2C series” in monoaminergic neurons.<br> Methods After the exposure to “2C series”, 2,5-dimethoxy-4-propylthiophenethylamine (2C-T-7), 2,5-dimethoxy-4-isopropylthiophenethylamine (2C-T-4), 2,5-dimethoxy-4-ethylthiophenthylamine (2C-T-2), 2,5-dimethoxy-4-iodophenethylamine (2C-I) or 2,5-dimethoxy-4-chlorophenethylamine (2C-C), we examined their neurotoxicity, morphological changes, and effects of concomitant exposure to 3,4-methylenedioxymethamphetamine (MDMA) or methamphetamine (METH), using cultured neuronal dopaminergic CATH.a cells and serotonin-containing B65 cells.<br> Results Single dose exposure to “2C series” for 24 h showed significant cytotoxicity as increase in lactate dehydrogenase (LDH) release from both monoaminergic neurons: 2C-T-7, 2C-C (EC50; 100 µM) > 2C-T-2 (150 µM), 2C-T-4 (200 µM) > 2C-I (250 µM) in CATH.a cells and 2C-T-7, 2C-I (150 µM) > 2C-T-2 (250 µM) > 2C-C, 2C-T-4 (300 µM) in B65 cells. The “2C series”-induced neurotoxicity in both cells was higher than that of MDMA or METH (EC50: ≥ 1–2 mM). In addition, apoptotic morphological changes were observed at relatively lower concentrations of “2C series”. The concomitant exposure to non-toxic dose of MDMA or METH synergistically enhanced 2C series drugs-induced LDH release and apoptotic changes in B65 cells, but to a lesser extent in CATH.a cells. In addition, the lower dose of 2C-T-7, 2C-T-2 or 2C-I promoted reactive oxygen species production in the mitochondria of B65 cells, even at the early stages (3 h) without apparent morphological changes.<br> Conclusion The 2,5-dimethoxy-substitution of “2C series” induced severe neurotoxicity in both dopaminergic and serotonin-containing neurons. The non-toxic dose of MDMA or METH synergistically enhanced its neurotoxicity in serotonergic neurons. No potential conflict of interest relevant to this article was reported.

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

Oxford University Press (OUP) Acta Medica Okayama 1347-6947 88 10 2024 Cytosolic acidification and oxidation are the toxic mechanisms of SO2 in Arabidopsis guard cells 1164 1171 EN Mahdi Mozhgani Institute of Plant Science and Resources, Okayama University Lia Ooi Institute of Plant Science and Resources, Okayama University Christelle Espagne Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC) Sophie Filleur Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC) Izumi C Mori Institute of Plant Science and Resources, Okayama University SO2/H2SO3 can damage plants. However, its toxic mechanism has still been controversial. Two models have been proposed, cytosolic acidification model and cellular oxidation model. Here, we assessed the toxic mechanism of H2SO3 in three cell types of Arabidopsis thaliana, mesophyll cells, guard cells (GCs), and petal cells. The sensitivity of GCs of Chloride channel a (CLCa)-knockout mutants to H2SO3 was significantly lower than those of wildtype plants. Expression of other CLC genes in mesophyll cells and petal cells were different from GCs. Treatment with antioxidant, disodium 4,5-dihydroxy-1,3-benzenedisulfonate (tiron), increased the median lethal concentration (LC50) of H2SO3 in GCs indicating the involvement of cellular oxidation, while the effect was negligible in mesophyll cells and petal cells. These results indicate that there are two toxic mechanisms of SO2 to Arabidopsis cells: cytosolic acidification and cellular oxidation, and the toxic mechanism may vary among cell types. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6694 16 15 2024 Utilizing the Metaverse to Provide Innovative Psychosocial Support for Pediatric, Adolescent, and Young Adult Patients with Rare Cancer 2617 EN Joe Hasei Department of Medical Information and Assistive Technology Development, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hisashi Ishida Department of Pediatrics, Okayama University Hospital Hideki Katayama Department of Palliative and Supportive Care, Okayama University Hospital Naoko Maeda Department of Pediatrics, NHO National Hospital Organization Nagoya Medical Center Akihito Nagano Department of Orthopedic Surgery, Graduate School of Medicine, Gifu University Motoharu Ochi Department of Pediatrics, Okayama University Hospital Masako Okamura Division of Survivorship, Institute for Cancer Control, National Cancer Center Shintaro Iwata Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital Kunihiro Ikuta Department of Orthopedic Surgery, Graduate School of Medicine, Nagoya University Shinichirou Yoshida Department of Orthopedic Surgery, Graduate School of Medicine, Tohoku University Tomohiro Fujiwara Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eiji Nakata Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuichi Nakahara Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyuki Kunisada Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University This study investigated the potential of the metaverse in providing psychological support for pediatric and AYA cancer patients, with a focus on those with rare cancers. The research involved ten cancer patients and survivors from four distinct regions in Japan, who participated in metaverse sessions using customizable avatars, facilitating interactions across geographical and temporal barriers. Surveys and qualitative feedback were collected to assess the psychosocial impact of the intervention. The results demonstrated that the metaverse enabled patients to connect with peers, share experiences, and receive emotional support. The anonymity provided by avatars helped reduce appearance-related anxiety and stigma associated with cancer treatment. A case study of a 19-year-old male with spinal Ewing’s sarcoma highlighted the profound emotional relief fostered by metaverse interactions. The findings suggest that integrating virtual spaces into healthcare models can effectively address the unique needs of pediatric and AYA cancer patients, offering a transformative approach to delivering psychosocial support and fostering a global patient community. This innovative intervention has the potential to revolutionize patient care in the digital age. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0022-3263 89 14 2024 Formal One Carbon Deletion of Indoline Hemiaminals under Tautomeric Control to Access 2-Aminobenzyl Compounds 10349 10354 EN Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Unprecedented tert-BuOK-mediated one carbon deletion of indoline hemiaminals has been achieved. This novel protocol provides an efficient synthetic tool for the construction of 2-aminobenzyl compounds with high chemoselectivity. In addition, functionalized 2-aminobenzyl compounds are difficult to make, for which few limited means of access currently exist. The key to success is the use of in situ generated Heyns rearrangement products (α-amino carbonyl compounds) as precursors for formal one carbon deletion. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2192-4449 14 1 2024 A case of membranous nephropathy complicated by Cronkhite–Canada syndrome successfully treated with mizoribine 72 80 EN Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shiho Morimoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Department of Chronic Kidney Disease and Cardiovascular Disease, 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 Cronkhite–Canada syndrome (CCS) is a non-hereditary disorder characterized by non-neoplastic hamartomatous gastrointestinal polyposis, hair loss, nail atrophy, hyperpigmentation, and diarrhea. While the relationship between CCS and nephritis remains unclear, seven cases of nephritis complicated by CCS have been reported to date, all of which were membranous nephropathy (MN). A 57-year-old man presented with taste disturbance, hair loss, nail plate atrophy, skin pigmentation, and frequent diarrhea. Endoscopic findings showed multiple polyposis of the stomach and large intestine. Given the above, he was diagnosed with CCS. The symptoms gradually improved with prednisolone treatment, although urinary protein and hypoproteinemia appeared during the tapering of prednisolone. He was diagnosed with MN using a renal biopsy, and immunofluorescence microscopy with IgG subclass staining showed predominantly diffuse granular capillary wall staining of IgG4. The cause of secondary MN was not found, including malignant tumors. Nephrotic-range proteinuria persisted despite treatment with prednisolone and cyclosporine. Additional treatment with mizoribine resulted in incomplete remission type 1 of nephrotic syndrome, suggesting that mizoribine may be a treatment option for patients with CCS with steroid-resistant MN. Considering a high prevalence of hypoproteinemia due to chronic diarrhea and protein-losing enteropathy in patients with CCS, proteinuria might be overlooked; thus, follow-up urinalysis would be recommended in patients with CCS. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1520-6106 128 27 2024 Bidirectional Optical Control of Proton Motive Force in Escherichia coli Using Microbial Rhodopsins 6509 6517 EN Kotaro Nakanishi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichi Kojima Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiyuki Sowa Department of Frontier Bioscience and Research Center for Micro-Nano Technology, Hosei University Yuki Sudo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Proton (H+) motive force (PMF) serves as the energy source for the flagellar motor rotation, crucial for microbial motility. Here, to control PMF using light, we introduced light-driven inward and outward proton pump rhodopsins, RmXeR and AR3, into Escherichia coli. The motility of E. coli cells expressing RmXeR and AR3 significantly decreased and increased upon illumination, respectively. Tethered cell experiments revealed that, upon illumination, the torque of the flagellar motor decreased to nearly zero (28 pN nm) with RmXeR, while it increased to 1170 pN nm with AR3. These alterations in PMF correspond to +146 mV (RmXeR) and −140 mV (AR3), respectively. Thus, bidirectional optical control of PMF in E. coli was successfully achieved by using proton pump rhodopsins. This system holds a potential for enhancing our understanding of the roles of PMF in various biological functions. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1613-4125 68 15 2024 Unabsorbed Fecal Fat Content Correlates with a Reduction of Immunoglobulin a Coating of Gut Bacteria in High‐Lard Diet‐Fed Mice 2400078 EN Emiko Katsumata Graduate School of Environmental and Life Science, Okayama University Takeshi Tsuruta Graduate School of Environmental and Life Science, Okayama University Kei Sonoyama Research Faculty of Agriculture, Hokkaido University Takashi Yoshida TAIYO YUSHI Corporation Mio Sasaki TAIYO YUSHI Corporation Mao Teraoka Graduate School of Environmental and Life Science, Okayama University Tianyang Wang Graduate School of Environmental and Life Science, Okayama University Naoki Nishino Graduate School of Environmental and Life Science, Okayama University Scope: Immunoglobulin A (IgA) selectively coats gut bacteria and contributes to regulatory functions in gastrointestinal inflammation and glucose metabolism. Excess intake of lard leads to decrease in the IgA coating of gut bacteria, although the underlying mechanisms remain unknown. This study validates how unabsorbed fat derived from a high-lard diet in the gut affects the IgA coating of bacteria, as assessed in mouse models using three types of dietary fat (lard, medium-, and long-chain triglycerides [MLCTs], and medium-chain triglycerides [MCTs]) exhibiting different digestibilities.<br> Methods and results: C57BL/6J mice are maintained on diets containing lard, MLCTs, or MCTs at 7% or 30% w/w for 10 weeks (n = 6 per group). The fecal fatty acid concentration is measured to quantify unabsorbed fat content. The ratio of IgA-coated bacteria to total bacteria (IgA coating ratio) in the feces is measured by flow cytometry. Compared to lard-fed mice, MLCT- and MCT-fed mice exhibit lower fecal concentrations of palmitic acid, stearic acid, and oleic acid and higher IgA coating ratios at both 7% and 30% dietary fat, and these parameters exhibit significant negative correlations.<br> Conclusion: Unabsorbed fat content in the gut may result in attenuated IgA coating of bacteria in high-lard diet-fed mice.<br> 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 0302-766X 391 2 2022 The medaka mutant deficient in eyes shut homolog exhibits opsin transport defects and enhanced autophagy in retinal photoreceptors 249 267 EN Keita Sato Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yang Liu Department of Cytology and Histology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takahiro Yamashita Department of Biophysics, Graduate School of Science, Kyoto University Hideyo Ohuchi Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Eyes shut homolog (EYS) encodes a proteoglycan and the human mutation causes retinitis pigmentosa type 25 (RP25) with progressive retinal degeneration. RP25 most frequently affects autosomal recessive RP patients with many ethnic backgrounds. Although studies using RP models have facilitated the development of therapeutic medications, Eys has been lost in rodent model animals. Here we examined the roles for Eys in the maintenance of photoreceptor structure and function by generating eys-null medaka fish using the CRISPR-Cas9 system. Medaka EYS protein was present near the connecting cilium of wild-type photoreceptors, while it was absent from the eys−/− retina. The mutant larvae exhibited a reduced visual motor response compared with wild-type. In contrast to reported eys-deficient zebrafish at the similar stage, no retinal cell death was detected in the 8-month post-hatching (8-mph) medaka eys mutant. Immunohistochemistry showed a significant reduction in the length of cone outer segments (OSs), retention of OS proteins in the inner segments of photoreceptors, and abnormal filamentous actin network at the base of cone OSs in the mutant retina by 8 mph. Electron microscopy revealed aberrant structure of calyceal processes, numerous vesiculation and lamellar interruptions, and autophagosomes in the eys-mutant cone photoreceptors. In situ hybridization showed an autophagy component gene, gabarap, was ectopically expressed in the eys-null retina. These results suggest eys is required for regeneration of OS, especially of cone photoreceptors, and transport of OS proteins by regulating actin filaments. Enhanced autophagy may delay the progression of retinal degeneration when lacking EYS in the medaka retina. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Intravenous infusion of cardiac progenitor cells in animal models of single ventricular physiology EN Takuya GOTO 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 Exploring tacit knowledge based on an expert nurse’s practice for stroke patients EN Satsuki OBAMA Graduate School of Health Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Breastfeeding at 6 months of age had a positive impact on overweight and obesity in Japanese adolescents at 15 years of age EN Tomoka KADOWAKI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Percentage of low attenuation area on computed tomography detects chronic lung allograft dysfunction, especially bronchiolitis obliterans syndrome, after bilateral lung transplantation EN Yujiro KUBO Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Development and validation of a symptom illustration scale from the patient-reported outcome common terminology criteria for adverse events for patients with breast cancer EN Yoko SUZUKI 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 A nationwide birth cohort in Japan showed increased risk of early childhood hospitalisation in infants born small for gestational age EN Asami OYAMA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 The effectiveness of simulation-based education combined with peer-assisted learning on clinical performance of first-year medical residents: a case-control study EN Taku MURAKAMI 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 Comparison between olanzapine and aripiprazole treatment for 104 weeks after hospital discharge in schizophrenia spectrum disorders: a multicenter retrospective cohort study in a real-world setting EN Tomonari HOSOKAWA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0003-6862 59 3 2024 Body-size-dependent predation by some jumping spider species (Araneae: Salticidae) on Tribolium castaneum (Coletptera: Tenebrionidae) 267 271 EN Toma Hayashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kentarou Matsumura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takahisa Miyatake Graduate School of Environmental, Life, Natural Science and Technology, Okayama University We examined the predation of two synanthropic jumping spiders, Hasarius adansoni (Araneae: Salticidae) and Plexippus paykulli (Araneae: Salticidae), on Tribolium castaneum (Herbst) (Coletptera: Tenebrionidae), a grain storage pest, that is sometimes found with these species to determine whether the predatory success of synanthropic and grassland jumping spiders on T. castaneum differs. We examined the predation of two synanthropic and three grassland jumping spiders on T. castaneum adults and larvae. We found that the two synanthropic species preyed on T. castaneum adults and larvae, while the three grassland species never attacked T. castaneum adults. The success or failure of predation on T. castaneum adults also depended on the body size of the jumping spiders. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0002-7863 146 22 2024 Skeletal Formation of Carbocycles with CO2: Selective Synthesis of Indolo[3,2-b]carbazoles or Cyclophanes from Indoles, CO2, and Phenylsilane 14935 14941 EN Sha Li Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Shoko Nakahara Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Taishin Adachi Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Takumi Murata Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Kazuto Takaishi Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Tadashi Ema Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University The catalytic reactions of indoles with CO2 and phenylsilane afforded indolo[3,2-b]carbazoles, where the fused benzene ring was constructed by forming two C–H bonds and four C–C bonds with two CO2 molecules via deoxygenative conversions. Nine-membered cyclophanes made up of three indoles and three CO2 molecules were also obtained, where the cyclophane framework was constructed by forming six C–H bonds and six C–C bonds. These multicomponent cascade reactions giving completely different carbocycles were switched simply by choosing the solvent, acetonitrile or ethyl acetate. No potential conflict of interest relevant to this article was reported.

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

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

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

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

Wiley Acta Medica Okayama 1086-9379 59 6 2024 Wetting property of Fe‐S melt in solid core: Implication for the core crystallization process in planetesimals 1314 1328 EN Shiori Matsubara Department of Earth Sciences, Graduate School of Science and Technology, Okayama University Hidenori Terasaki Department of Earth Sciences, Graduate School of Science and Technology, Okayama University Takashi Yoshino Institute for Planetary Materials, Okayama University Satoru Urakawa Department of Earth Sciences, Graduate School of Science and Technology, Okayama University Daisuke Yumitori Department of Earth Sciences, Graduate School of Science and Technology, Okayama University In differentiated planetesimals, the liquid core starts to crystallize during secular cooling, followed by the separation of liquid–solid phases in the core. The wetting property between liquid and solid iron alloys determines whether the core melts are trapped in the solid core or they can separate from the solid core during core crystallization. In this study, we performed high-pressure experiments under the conditions of the interior of small bodies (0.5–3.0 GPa) to study the wetting property (dihedral angle) between solid Fe and liquid Fe-S as a function of pressure and duration. The measured dihedral angles are approximately constant after 2 h and decrease with increasing pressure. The dihedral angles range from 30° to 48°, which are below the percolation threshold of 60° at 0.5–3.0 GPa. The oxygen content in the melt decreases with increasing pressure and there are strong positive correlations between the S + O or O content and the dihedral angle. Therefore, the change in the dihedral angle is likely controlled by the O content of the Fe-S melt, and the dihedral angle tends to decrease with decreasing O content in the Fe-S melt. Consequently, the Fe-S melt can form interconnected networks in the solid core. In the obtained range of the dihedral angle, a certain amount of the Fe-S melt can stably coexist with solid Fe, which would correspond to the “trapped melt” in iron meteorites. Excess amounts of the melt would migrate from the solid core over a long period of core crystallization in planetesimals. No potential conflict of interest relevant to this article was reported.

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

MDPI Acta Medica Okayama 2077-0383 12 22 2023 Epidemiology and Reporting Characteristics of Systematic Reviews in Orthopedic Journals: A Meta-Epidemiological Study 7031 EN Norio Yamamoto Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunsuke Taito Scientific Research WorkS Peer Support Group (SRWS-PSG) Takanori Miura Scientific Research WorkS Peer Support Group (SRWS-PSG) Takashi Ariie Scientific Research WorkS Peer Support Group (SRWS-PSG) Yosuke Tomita Department of Physical Therapy, Faculty of Health Care, Takasaki University of Health and Welfare Hirofumi Ogihara Scientific Research WorkS Peer Support Group (SRWS-PSG) Daijo Shiratsuchi Graduate School of Health Sciences, Kagoshima University Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasushi Tsujimoto Scientific Research WorkS Peer Support Group (SRWS-PSG) Systematic reviews (SRs) with complete reporting or rigorous methods can lead to less biased recommendations and decisions. A comprehensive analysis of the epidemiological and reporting characteristics of SRs in orthopedics is lacking. We evaluated 360 SRs, including 165 and 195 published in orthopedic journals in 2012 and 2022. According to the established reporting guidelines, we examined these SRs for key epidemiological characteristics, including focus areas, type of meta-analysis (MA), and reporting characteristics. Most SRs (71%) were therapy-related, with a significant proportion originating from authors in the USA, UK, and China. Pairwise MA was performed on half of the SRs. The proportion of protocol registrations improved by 2022 but remained low (33%). Despite a formal declaration of adherence to the reporting guidelines (68%), they were often not used and reported enough. Only 10% of the studies used full search strategies, including trial registries. Publication bias assessments, subgroup analyses, and sensitivity analyses were not even planned. The risk of bias assessment improved in 2022; however, the certainty of the evidence remained largely unassessed (8%). The use and reporting of standard methods in orthopedic SRs have remained suboptimal. Thus, authors, peer reviewers, journal editors, and readers should criticize the results more. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1865-0333 17 1 2024 Evaluation of attenuation correction method for head holder in brain perfusion single-photon emission computed tomography 322 328 EN Masahiro Nakashima ivision of Radiological Technology, Okayama University Hospital Yuta Yamazaki Canon Medical Systems Corporation Head holder attenuation affects brain perfusion single-photon emission computed tomography (SPECT) image quality. Here, we proposed a head holder-attenuation correction (AC) method using attenuation coefficient maps calculated by Chang’s method from CT images. Then, we evaluated the effectiveness of the head holder-AC method by numerical phantom and clinical cerebral perfusion SPECT studies. In the numerical phantom, the posterior counts were 10.7% lower than the anterior counts without head holder-AC method. However, by performing head holder-AC, the posterior count recovered by approximately 6.8%, approaching the true value. In the clinical study, the normalized count ratio was significantly increased by performing the head holder-AC method in the posterior-middle cerebral artery, posterior cerebral artery and cerebellum regions. There were no significant increases in other regions. The head holder-AC method can correct the counts attenuated by the head holder. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2210-7703 46 2 2024 A comparison between the adverse event profiles of patients receiving palbociclib and abemaciclib: analysis of two real-world databases 536 541 EN Tatsuaki Takeda Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Shiho Sugimoto Department of Personalized Medicine and Preventive Healthcare Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Matsumoto Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Naohiro Iwata Department of Pharmacy, Okayama University Hospital Akihiko Nakamoto Department of Pharmacy, Okayama University Hospital Aya Fukuma Ozaki Department of Clinical Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University of California Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Noritaka Ariyoshi Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Background Palbociclib and abemaciclib are cyclin-dependent kinase (CDK) 4/6 inhibitors currently used to treat breast cancer. Although their therapeutic efficacies are considered comparable, differences in adverse event (AE) profiles of the two drugs remain unclear.<br> Aim We analysed two real-world databases, the World Health Organization’s VigiBase and the Food and Drug Administration Adverse Event Reporting System (FAERS), to identify differences in AE profiles of palbociclib and abemaciclib.<br> Method Data of patients with breast cancer receiving palbociclib or abemaciclib recorded until December 2022 were extracted from the VigiBase and FAERS databases. In total, 200 types of AEs were analysed. The reporting odds ratios were calculated using a disproportionality analysis.<br> Results Cytopenia was frequently reported in patients receiving palbociclib, whereas interstitial lung disease and diarrhoea were frequently reported in those receiving abemaciclib. Moreover, psychiatric and nervous system disorders were more common in the palbociclib group, whereas renal and urinary disorders were more common in the abemaciclib group.<br> Conclusion This study is the first to show comprehensively the disparities in the AE profiles of palbociclib and abemaciclib. The findings highlight the importance of considering these differences when selecting a suitable CDK4/6 inhibitor to ensure safe and favourable outcomes for patients with breast cancer. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0947-6539 30 11 2024 On Demand Synthesis of C3−N1’ Bisindoles by a Formal Umpolung Strategy: First Total Synthesis of (±)‐Rivularin A e202302963 EN Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University In this work, a straightforward synthesis of C3−N1’ bisindolines is achieved by a formal umpolung strategy. The protocols were tolerant of a wide variety of substituents on the indole and indoline ring. In addition, the C3−N1’ bisindolines could be converted to C3−N1’ indole-indolines and C3−N1’-bisindoles. Also, we have successfully synthesized (±)-rivularin A through a biomimetic late-stage tribromination as a key step. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0942-2056 32 1 2024 Intercondylar notch width and osteophyte width impact meniscal healing and clinical outcomes following transtibial pullout repair of medial meniscus posterior root tears 116 123 EN Takaaki Hiranaka Department of Orthopaedic Surgery, Okayama University Hospital Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Hospital Yusuke Yokoyama Department of Orthopaedic Surgery, Okayama University Hospital Naohiro Higashihara Department of Orthopaedic Surgery, Okayama University Hospital Masanori Tamura Department of Orthopaedic Surgery, Okayama University Hospital Koki Kawada Department of Orthopaedic Surgery, Okayama University Hospital Haowei Xue Department of Orthopaedic Surgery, Okayama University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Hospital Purpose: This retrospective study aimed to investigate the relationship between intercondylar notch width (ICNW), osteophyte width (OW), and the healing of medial meniscus posterior root tears (MMPRTs) following arthroscopic pullout repair.<br> Methods: The study included 155 patients diagnosed with MMPRTs who underwent transtibial pullout repair. Meniscal healing status was evaluated on second-look arthroscopy using a previously reported meniscus healing score. Patients were divided into two groups based on this score: the high healing score (group HH, healing score ≥ 8 points) and suboptimal healing score (group SO, healing score ≤ 6 points) groups. Computed tomography scans were performed on patients 1 week postsurgery. ICNW and OW widths were measured and relatively evaluated based on their ratio to the intercondylar distance (ICD), represented as the ICNW/ICD ratio (%) and OW/ICD ratio (%), respectively. Patient-reported outcomes were assessed preoperatively and on second-look arthroscopy using the Knee injury and Osteoarthritis Outcome Score (KOOS) and visual analogue scale (VAS).<br> Results: There were no significant demographic differences between the SO and HH group (n = 35 and 120 patients, respectively). Regarding radiographic measurements, significant differences were observed in the ICNW/ICD ratio (group SO, 24.2%; group HH, 25.2%; p = 0.024), OW (group SO, 2.6 mm; group HH, 2.0 mm; p < 0.001), and OW/ICD ratio (group SO, 3.5%; group HH, 2.7%; p < 0.001). Both groups had similar preoperative clinical scores, but postoperative clinical scores, including KOOS-activities of daily living (group SO, 83.4; group HH, 88.7; p = 0.035) and VAS (group SO, 19.1; group HH, 11.3; p = 0.005), were significantly better in group HH.<br> Conclusion: The study suggests that ICNW and OW may play a crucial role in MMPRT healing following arthroscopic pullout repair, as evidenced by the worse clinical outcomes associated with a narrower ICNW and wider OW. These findings highlight the potential significance of ICNW and OW assessments when evaluating meniscal repair indications. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1549-9596 64 2 2023 pSPICA Force Field Extended for Proteins and Peptides 532 542 EN Yusuke Miyazaki Research Institute for Interdisciplinary Science, Okayama University Wataru Shinoda Research Institute for Interdisciplinary Science, Okayama University Many coarse-grained (CG) molecular dynamics (MD) studies have been performed to investigate biological processes involving proteins and lipids. CG force fields (FFs) in these MD studies often use implicit or nonpolar water models to reduce computational costs. CG-MD using water models cannot properly describe electrostatic screening effects owing to the hydration of ionic segments and thus cannot appropriately describe molecular events involving water channels and pores through lipid membranes. To overcome this issue, we developed a protein model in the pSPICA FF, in which a polar CG water model showing the proper dielectric response was adopted. The developed CG model greatly improved the transfer free energy profiles of charged side chain analogues across the lipid membrane. Application studies on melittin-induced membrane pores and mechanosensitive channels in lipid membranes demonstrated that CG-MDs using the pSPICA FF correctly reproduced the structure and stability of the pores and channels. Furthermore, the adsorption behavior of the highly charged nona-arginine peptides on lipid membranes changed with salt concentration, indicating the pSPICA FF is also useful for simulating protein adsorption on membrane surfaces. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 0114-5916 47 3 2023 International Trends in Adverse Drug Event-Related Mortality from 2001 to 2019: An Analysis of the World Health Organization Mortality Database from 54 Countries 237 249 EN Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Shunya Iinuma Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Michio Yamamoto Graduate School of Human Sciences, Osaka University, Osaka, Japan RIKEN Center for Advanced Intelligence Project, Takahiro Niimura Department of Clinical Pharmacology and Therapeutics, Institute of Biomedical Sciences, Tokushima University Graduate School Yuka Osaki Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Sayoko Nishimura Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Ko Harada Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel Yoshito Zamami Department of Pharmacy, Okayama University Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background and Objective<br> Adverse drug events (ADEs) are becoming a significant public health issue. However, reports on ADE-related mortality are limited to national-level evaluations. Therefore, we aimed to reveal overall trends in ADE-related mortality across the 21st century on an international level.<br> Methods<br> This observational study analysed long-term trends in ADE-related mortality rates from 2001 to 2019 using the World Health Organization Mortality Database. The rates were analysed according to sex, age and region. North America, Latin America and the Caribbean, Western Europe, Eastern Europe and Western Pacific regions were assessed. Fifty-four countries were included with four-character International Statistical Classification of Disease and Related Health Problems, Tenth Revision codes in the database, population data in the World Population Prospects 2019 report, mortality data in more than half of the study period, and high-quality or medium-quality death registration data. A locally weighted regression curve was used to show international trends in age-standardised rates.<br> Results<br> The global ADE-related mortality rate per 100,000 population increased from 2.05 (95% confidence interval 0.92–3.18) in 2001 to 6.86 (95% confidence interval 5.76–7.95) in 2019. Mortality rates were higher among men than among women, especially in those aged 20–50 years. The population aged ≥ 75 years had higher ADE-related mortality rates than the younger population. North America had the highest mortality rate among the five regions. The global ADE-related mortality rate increased by approximately 3.3-fold from 2001 to 2019.<br> Conclusions<br> The burden of ADEs has increased internationally with rising mortality rates. Establishing pharmacovigilance systems can facilitate efforts to reduce ADE-related mortality rates globally. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0942-2056 32 1 2024 Weight loss enhances meniscal healing following transtibial pullout repair for medial meniscus posterior root tears 143 150 EN Takaaki Hiranaka Department of Orthopaedic Surgery, Okayama University Hospital Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Hospital Yusuke Yokoyama Department of Orthopaedic Surgery, Okayama University Hospital Naohiro Higashihara Department of Orthopaedic Surgery, Okayama University Hospital Masanori Tamura Department of Orthopaedic Surgery, Okayama University Hospital Koki Kawada Department of Orthopaedic Surgery, Okayama University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Hospital Purpose: This study investigated the impact of weight change on the success of transtibial pullout repair for medial meniscus (MM) posterior root tears (MMPRTs).<br> Methods: The study included 129 patients diagnosed with MMPRTs who had undergone transtibial pullout repair. The patients were screened between July 2018 and November 2021. Patient-reported outcomes were assessed preoperatively and at 12 months postoperatively using the Knee injury and Osteoarthritis Outcome Score (KOOS). MM extrusion (MME) and ΔMME (postoperative MME – preoperative MME) were calculated preoperatively and at 12 months postoperatively using magnetic resonance imaging.<br> Results: Patients were divided into weight loss (body mass index [BMI] decrease of at least 0.5 kg/m2 after primary repair; n = 63) and weight gain (BMI increase of at least 0.5 kg/m2; n = 66) groups. Both groups had similar demographic variables and preoperative clinical scores; patient-reported outcomes significantly improved postoperatively. The weight loss group had significantly greater improvement in KOOS–quality of life (weight loss, 29.4 ± 23.7; weight gain, 23.9 ± 27.6; p = 0.034), lower postoperative MME (weight loss, 3.9 ± 1.7 mm; weight gain, 4.2 ± 1.2 mm; p = 0.043) and lower ΔMME (weight loss, 0.8 ± 0.8 mm; weight gain, 1.2 ± 0.9 mm; p = 0.002) than the weight gain group. Total arthroscopic healing scores (weight loss, 7.6 ± 1.0; weight gain, 7.2 ± 1.5; p = 0.048) and associated subscales, including anteroposterior bridging tissue width (weight loss, 4.0 ± 0.0; weight gain, 3.8 ± 0.7; p = 0.004) and MM posterior root stability (weight loss, 2.6 ± 0.7; weight gain, 2.4 ± 0.7; p = 0.041), significantly differed between the groups.<br> Conclusions: Weight loss was associated with better meniscal healing and less MME progression after MMPRT repair, highlighting the significance of weight management in individuals undergoing meniscal surgery. These findings provide valuable insights into the clinical significance of weight loss in the success of transtibial pullout repair for MMPRTs. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1552-4825 194 5 2023 Radiological characteristics of skeletal growth in neonates and infants with achondroplasia e63525 EN Daisuke Miyahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Yuko Ago Department of Pediatrics, Okayama University Hospital Natsuko Futagawa Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Miyahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yousuke Higuchi Department of Pediatrics, Okayama University Hospital Kazuki Yamada Department of Orthopedics, Okayama University Hospital Tomonori Tetsunaga Department of Orthopedics, Okayama University Hospital Tadashi Moriwake Department of Pediatrics, Iwakuni Clinical Center, National Hospital Organization Hiroyuki Tanaka Department of Pediatrics, Okayama Saiseikai General Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Achondroplasia (ACH) is the most common form of skeletal dysplasia characterized by a rhizomelic short stature. Radiological skeletal findings in pediatric and adult patients with ACH include short long bones, a relatively longer fibula compared to the tibia, a narrow lumbar interpedicular distance, and a hypoplastic iliac wing. Nonetheless, the characteristics of skeletal growth during the neonatal and infantile periods have scarcely been explored. Therefore, this retrospective study aimed to analyze the radiological skeletal growth during the neonatal and infantile periods in 41 Japanese patients with genetically confirmed ACH. The length of long bones in the upper and lower limbs and the lumbar interpedicular distances at L1 and L4 were measured. These parameters showed significant positive correlations with age. The upper segment-to-lower segment ratio in the lower limbs resembled the data of healthy controls from previous reports. The L1/L4 and fibula/tibia ratios increased with age, suggesting that some representative skeletal phenotypes of ACH were less distinct during the neonatal and infantile periods. In conclusion, for the first time, this study radiologically characterized skeletal growth during the neonatal and infantile periods of patients with genetically confirmed ACH. 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.<br> 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.<br> 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.<br> 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.<br> No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1434-193X 27 4 2023 Concise Synthesis of Thiazolo[4,5-b]indoles via Ring Switch/Cyclization Sequences e202301130 EN Koji Yamada Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Tetsu Tsubogo Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Hikaru Kanazawa Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Sayaka Ishizuka Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Koutaro Ohyama Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Masaki Kaida Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The unexpected reactions of indoline hemiaminals affords 2,5-diaryl-4-hydroxythiazolines through a thioamidation/ring switch sequence. The key to success of this transformation is to use a thioamide as a thiazoline precursor under transient tautomeric control. This transformation features mild reaction conditions and good yields with broad functional group tolerance (17 examples, up to 99 % yield). Further transformations of the thiazolines provide a direct entry to dihydrothiazolo[4,5-b]indoles and thiazolo[4,5-b]indoles. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1436-2228 25 6 2023 Nuclear Transformation of the Marine Pennate Diatom Nitzschia sp. Strain NIES-4635 by Multi-Pulse Electroporation 1208 1219 EN Koki Okada Graduate School of Environmental and Life Science, Okayama University Yu Morimoto Graduate School of Environmental and Life Science, Okayama University Yukine Shiraishi Graduate School of Environmental and Life Science, Okayama University Takashi Tamura Faculty of Environmental, Life, Natural Science and Technology, Okayama University Shigeki Mayama The Advanced Support Center for Science Teachers, Tokyo Gakugei University Takashi Kadono Faculty of Agriculture and Marine Science, Kochi University Masao Adachi Faculty of Agriculture and Marine Science, Kochi University Kentaro Ifuku Graduate School of Agriculture, Kyoto University Michiko Nemoto Faculty of Environmental, Life, Natural Science and Technology, Okayama University Nitzschia is one of the largest genera of diatoms found in a range of aquatic environments, from freshwater to seawater. This genus contains evolutionarily and ecologically unique species, such as those that have lost photosynthetic capacity or those that live symbiotically in dinoflagellates. Several Nitzschia species have been used as indicators of water pollution. Recently, Nitzschia species have attracted considerable attention in the field of biotechnology. In this study, a transformation method for the marine pennate diatom Nitzschia sp. strain NIES-4635, isolated from the coastal Seto Inland Sea, was established. Plasmids containing the promoter/terminator of the fucoxanthin chlorophyll a/c binding protein gene (fcp, or Lhcf) derived from Nitzschia palea were constructed and introduced into cells by multi-pulse electroporation, resulting in 500 μg/mL nourseothricin-resistant transformants with transformation frequencies of up to 365 colonies per 108 cells. In addition, when transformation was performed using a new plasmid containing a promoter derived from a diatom-infecting virus upstream of the green fluorescent protein gene (gfp), 44% of the nourseothricin-resistant clones exhibited GFP fluorescence. The integration of the genes introduced into the genomes of the transformants was confirmed by Southern blotting. The Nitzschia transformation method established in this study will enable the transformation this species, thus allowing the functional analysis of genes from the genus Nitzschia, which are important species for environmental and biotechnological development. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0902-0063 38 1 2023 Impact of changes in skeletal muscle mass and quality during the waiting time on outcomes of lung transplantation e15169 EN Akikazu Hagiyama Division of Physical Medicine and Rehabilitation, Okayama University Hospital Seiichiro Sugimoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin Tanaka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kei Matsubara Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshimi Katayama Division of Physical Medicine and Rehabilitation, Okayama University Hospital Masanori Hamada Division of Physical Medicine and Rehabilitation, Okayama University Hospital Masuo Senda Division of Physical Medicine and Rehabilitation, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Introduction: The association of changes in skeletal muscle mass and quality during the waiting time with outcomes of lung transplantation (LT) remains unclear. We aimed to examine the association of changes in skeletal muscle mass and quality during the waiting time, as well as preoperative skeletal muscle mass and quality, with outcomes of LT.<br> Methods: This study included individuals who underwent LT from brain-dead donors. Skeletal muscle mass (cm2/m2) and quality (mean Hounsfield units [HU]) of the erector spinae muscle at the 12th thoracic level were evaluated using computed tomography. Preoperative skeletal muscle mass and quality, and their changes during the waiting time were calculated. We evaluated the associations among mechanical ventilation (MV) duration, intensive care unit (ICU) length of stay (LOS), hospital LOS, 6-minute walk distance at discharge, and 5-year survival after LT.<br> Results: This study included 98 patients. The median waiting time was 594.5 days (interquartile range [IQR], 355.0–913.0). The median changes in skeletal muscle mass and quality were −4.4% (IQR, −13.3–3.1) and −2.9% (IQR, −16.0–4.1), respectively. Severe low skeletal muscle mass at LT was associated with prolonged ICU LOS (B = 8.46, 95% confidence interval [CI]: .51–16.42) and hospital LOS (B = 36.00, 95% CI: 3.23–68.78). Pronounced decrease in skeletal muscle mass during the waiting time was associated with prolonged MV duration (B = 7.85, 95% CI: .89–14.81) and ICU LOS (B = 7.97, 95% CI: .83–15.10).<br> Conclusion: Maintaining or increasing skeletal muscle mass during the waiting time would be beneficial to improve the short-term outcomes of LT. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1472-6920 23 1 2023 The effectiveness of simulation-based education combined with peer-assisted learning on clinical performance of first-year medical residents: a case-control study 859 EN Taku Murakami Department of General Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Akira Yamamoto Department of Hematology and Oncology, Okayama University Hospital Hideharu Hagiya Department of General Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Mikako Obika Department of General Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuhiro Mandai Department of Emergency Medicine, The JIKEI University Tomoko Miyoshi Department of General Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hitomi Kataoka Diversity Enhancement Center, Okayama University Hospital Fumio Otsuka Department of General Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Background Simulation-based education and peer-assisted learning (PAL) are both known as useful educational methods. Previous research has reported that combining these two methods are effective for training medical residents in short-term evaluation. This study was aimed to evaluate the middle- to long-term effects of simulation-based education combined with PAL on the performance of medical residents during emergency department duties.<br> Methods This study was designed as a case-control study and conducted over three years at Okayama University Hospital in Japan. Postgraduate-year-one medical residents were assigned to three groups: a simulation group that received simulation-based education, a lecture group that received traditional lecture-based education, and a control group that received no such prior trainings. Prior training in emergency department duties using PAL was performed as an educational intervention for the simulation and lecture groups during the clinical orientation period. The residents' medical knowledge was assessed by written examinations before and after the orientation. The performance of residents during their emergency department duties was assessed by self-evaluation questionnaires and objective-assessment checklists, following up with the residents for three months after the orientation period and collecting data on their 1st, 2nd, and 3rd emergency department duties. All the datasets collected were statistically analyzed and compared by their mean values among the three groups.<br> Results A total of 75 residents were included in the comparative study: 27 in the simulation group, 24 in the lecture group, and 24 in the control group. The simulation and lecture groups obtained significantly higher written examination scores than the control group. From the self-evaluation questionnaires, the simulation group reported significantly higher satisfaction in their prior training than the lecture group. No significant differences were found in the emergency department performance of the residents among the three groups. However, when evaluating the improvement rate of performance over time, all three groups showed improvement in the subjective evaluation, and only the simulation and lecture groups showed improvement in the objective evaluation.ConclusionSimulation-based education combined with PAL is effective in improving the knowledge and satisfaction of medical residents, suggesting the possibility of improving work performance during their emergency department duties. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1328-8067 65 1 2023 Adverse reactions in young children receiving the coronavirus disease 2019 vaccine e15696 EN Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junya Shimizu Department of Pediatrics, National Hospital Organization, Okayama Medical Center Yuji Yokoyama Department of Pediatrics, Okayama Aiiku Clinic Hirokazu Tsukahara Department of Pediatrics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: We sought to investigate the occurrence of adverse reactions in Japanese children aged 6 months to 4 years who received the BNT162b2 coronavirus disease 2019 (COVID-19) vaccine, to examine parental considerations, and to evaluate potential risk factors associated with post-vaccination fever.<br> Methods: This cross-sectional survey study targeted 1617 children aged 6 months to 4 years who received their primary doses of BNT162b2 from November 10, 2022, to April 30, 2023, in Okayama Prefecture. We surveyed the occurrence of local and systemic reactions within 1 week after vaccination, and described the incidence proportions of adverse reactions for 515 participants overall and by age group. The study also examined the impact of previous COVID-19 infection and co-administration of the seasonal influenza vaccine on post-vaccination fever. A survey also assessed parents' reasons for vaccinating their children and the sources of information they used.<br> Results: Adverse reactions were infrequent (5.2%, with fever ≥37.5°C; no cases exceeded 39°C) and did not increase with vaccine doses administered. The risk of post-vaccination fever was not statistically associated with a history of COVID-19―the adjusted risk ratio (aRR) was 0.99, and the 95% confidence interval (CI) was 0.41–2.39―but was associated with co-administration of the seasonal influenza vaccine (aRR 3.24, 95% CI 1.14–9.18). Parental decisions regarding vaccination were influenced by official government guidelines and primary care physicians' opinion.<br> Conclusion: This study provides valuable insight into the safety profile of the BNT162b2 vaccine in Japanese children aged 6 months to 4 years. Further research involving larger cohorts and appropriate control groups is needed. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0743-7463 39 44 2023 Analysis of Evaporation of Droplet Pairs by a Quasi-Steady-State Diffusion Model Coupled with the Evaporative Cooling Effect 15587 15596 EN Yutaka Yamada Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kazuma Isobe Faculty of Environmental, Life, Natural Science and Technology, Okayama University Akihiko Horibe Faculty of Environmental, Life, Natural Science and Technology, Okayama University Multidroplet evaporation is a common phase-change phenomenon not only in nature but also in many industrial applications, including inkjet printing and spray cooling. The evaporation behavior of these droplets is strongly affected by the distance between neighboring droplets, and in particular, evaporation suppression occurs as the distance decreases. However, further quantitative information, such as the temperature and local evaporation flux, is limited because the analytical models of multidroplet evaporation only treat vapor diffusion, and the effect of the latent heat transfer through the liquid–vapor phase change is ignored. Here, we perform a numerical analysis of evaporating droplet pairs that linked vapor diffusion from the droplet surface and evaporative cooling. Heat transfer through the liquid and gas phases is also considered because the saturation pressure depends on the temperature. The results show an increase in the vapor concentration in the region between the two droplets. Consequently, the local evaporation flux in the proximate region significantly decreases with decreasing separation distance. This means that the latent heat transfer through the phase change is diminished, and an asymmetrical temperature distribution occurs in the liquid and gas phases. These numerical results provide quantitative information about the temperature and local evaporation flux of evaporating droplet pairs, and they will guide further investigation of multiple droplet evaporation. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1434-193X 26 47 2023 Electrochemical Coupling Reactions Using Non‐Transition Metal Mediators: Recent Advances e202300835 EN Koichi Mitsudo Division of Applied Chemistry Graduate School of Environmental Life, Natural Science and Technology, Okayama University Yasuyuki Okumura Division of Applied Chemistry Graduate School of Environmental Life, Natural Science and Technology, Okayama University Eisuke Sato Division of Applied Chemistry Graduate School of Environmental Life, Natural Science and Technology, Okayama University Seiji Suga Division of Applied Chemistry Graduate School of Environmental Life, Natural Science and Technology, Okayama University Indirect electrolysis method using appropriate mediators enables numerous chemical reactions. The general principles of mediators were described herein with a particular focus on non-transition metal mediators. Recent representative examples of bond formation reactions by indirect electrolysis are summarized and discussed here. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Efficacy of prophylactic high-flow nasal cannula therapy for postoperative pulmonary complications after pediatric cardiac surgery: a prospective single-arm study EN Tatsuhiko SHIMIZU 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 Donor’s long-term quality of life following living-donor lobar lung transplantation EN Kento FUJII Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

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

Acta Medica Okayama 2023 Concomitant posterior anchoring further reduces posterior meniscal extrusion during pullout repair of medial meniscus posterior root tears: a retrospective study EN HAOWEI XUE 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.

Springer Science and Business Media LLC Acta Medica Okayama 0021-5155 67 3 2023 A nationwide survey of newly certified visually impaired individuals in Japan for the fiscal year 2019: impact of the revision of criteria for visual impairment certification 346 352 EN Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriko Morimoto Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Kawasaki Department of Vision Informatics, Osaka University Graduate School of Medicine Miyuki Fujiwara Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keisuke Kanenaga Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidetoshi Yamashita Yamagata City Institute of Public Health Taiji Sakamoto Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose　To determine the status of visual impairment certification in Japan in the fiscal year 2019 and the impact of revising the criteria for visual impairment certification implemented in 2018.<br> Study Design　Observational cross-sectional study.<br> Methods　We requested welfare offices throughout Japan to submit data of age, sex, causative diseases, and visual impairment grades for newly certified visually impaired individuals aged ≥ 18 years during the fiscal year 2019. The certification was based on criteria of the Act on Welfare of Physically Disabled Persons.<br> Results　Altogether, data were collected for 16,504 newly certified visually impaired individuals. The most common age group was 80–89 years (29.6%), followed by 70–79 (28.2%) and 60–69 (15.3%) years. The most common causative disease was glaucoma (40.7%), followed by retinitis pigmentosa (13.0%), diabetic retinopathy (10.2%), and macular degeneration (9.1%). The most common impairment grade was grade 2 (40.8%), followed by 5 (21.2%) and 1 (17.0%). Compared to the fiscal year 2015, there was a considerable increase in the number of individuals certified with glaucoma in the fiscal year 2019. Moreover, there was a significant increase in the number of individuals with certified grades 1 and 2 visual impairment, with a decrease in the number of individuals with certified grade 6 visual impairment.<br> Conclusion　The changes revealed in this study were primarily due to the revised certification criteria implemented in July 2018, indicating that it is important to review the certification criteria and to repeat surveys similar to the present study. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0721-832X 259 9 2021 Assessment of epiretinal membrane formation using en face optical coherence tomography after rhegmatogenous retinal detachment repair 2503 2512 EN Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Kanzaki Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichiro Doi Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sayumi Kanzaki Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Kimura Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mio Morizane Hosokawa Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Shiode Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosuke Takahashi Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose　To investigate epiretinal membrane (ERM) formation using en face optical coherence tomography (OCT) after vitrectomy for rhegmatogenous retinal detachment (RRD).<br> Methods　We retrospectively reviewed the medical records of 64 consecutive eyes (64 patients) with RRD treated by vitrectomy without ERM and internal limiting membrane peeling. ERMs and retinal folds were detected by B-scan and en face imaging. The maximum depth of retinal folds (MDRF) was quantified using en face imaging. ERM severity was staged using B-scan imaging. Main outcome measures were ERM detection rate with B-scan and en face imaging, MDRF, ERM staging, postoperative best-corrected visual acuity (BCVA; logarithm of the minimum angle of resolution), and risk factors for ERM formation.<br> Results　The detection rate for ERM formation was significantly higher with en face imaging (70.3%) than with B-scan imaging (46.9%; P = 0.007). There was no significant difference in postoperative BCVA between eyes with ERM formation (0.06 ± 0.26) and those without ERM formation (0.01 ± 0.14; P = 0.298). Forty of 45 (88.9%) eyes with ERM formation were classified as stage 1. Twenty-seven of 45 (60.0%) eyes with ERM formation developed parafoveal retinal folds. The mean MDRF was 27.4 ± 32.2 μm. Multiple retinal breaks and a maximum retinal break size of ≥ 2 disc diameters were significantly associated with ERM formation (P = 0.033 and P = 0.031, respectively).<br> Conclusion　Although ERM formation was observed in 70.3% patients after RRD repair, the formed ERM was not severe and had minimal impact on the postoperative visual acuity. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0721-832X 262 2 2023 Evaluation of epiretinal membrane formation after scleral buckling for treating rhegmatogenous retinal detachment: En face optical coherence tomography image-based study 469 476 EN Ryo Matoba Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Kanzaki Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tetsuro Morita Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shuhei Kimura Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mio Morizane Hosokawa Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Shiode Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Morizane Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose　To assess epiretinal membrane (ERM) formation, severity, and the associated risk factors after scleral buckling using en face optical coherence tomography (OCT) images.<br> Methods　Medical records of 61 consecutive patients (66 eyes) with rhegmatogenous retinal detachment who underwent scleral buckling were retrospectively reviewed. Posterior vitreous detachment (PVD) was determined based on B-scan OCT images. En face OCT images were used to visualize the ERM and retinal folds. ERM formation was identified by comparing en face images pre- and post-surgery. The maximum depth of the retinal folds (MDRF) was measured using en face imaging to objectively assess traction strength.<br> Results　ERM formation occurred in 15 (22.7%) eyes at the final visit; the foveal pit was preserved in all cases. Parafoveal retinal folds were present in 5 (7.6%) eyes, with a mean MDRF of 21.8 ± 12.6 µm. No significant difference was observed in best-corrected visual acuity (logarithm of the minimal angle of resolution) between the ERM formation (-0.019 ± 0.128) and non-ERM formation (-0.001 ± 0.213) groups at the final visit (P = 0.593; Mann-Whitney U test). Multivariate logistic regression analysis revealed that older age and the presence of PVD were significant risk factors for ERM formation (odds ratio 1.07, 95% confidence interval 1.01–1.14, P = 0.032; odds ratio 5.26, 95% confidence interval 1.06–26.10, P = 0.042; respectively).<br> Conclusion　ERM occurred in 22.7% of cases but was mild and did not affect visual acuity. Older age and the presence of PVD are risk factors for ERM formation. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2365-6549 8 31 2023 Polymer Template Synthesis of CuOx/Clay Nanocomposites with Controllable CuOx Formation e202301644 EN Yuki Takeuchi Inorganic Chemistry Laboratory, Graduate School of Natural Science & Technology, Okayama University Takahiro Ohkubo Inorganic Chemistry Laboratory, Graduate School of Natural Science & Technology, Okayama University Metal oxides have the excellent functions including high thermal stability, electrical properties, catalytic performance, and adsorption properties of acid gases such as CO2 via the acid-base interactions. However, they suffer from low reserves, porosity control, and low adsorption efficiency per weight compared with lightweight materials including carbon and silica. To solve these issues, various methods for supporting metal oxides on porous carriers, such as decomposition-precipitation and impregnation, have been investigated, but controlling the formation of metal oxide on clay nanosheets remains as a challenge. Herein, we developed a soft-template method for supporting metal oxide (CuOx) nanoparticles on activated clay nanosheets. The intercalation of polyethyleneimine (PEI)−Cu2+ complexes between the layers of clay nanosheets followed by calcination to construct CuOx and remove the PEI templates afforded CuOx/clay nanocomposites. The constructed CuOx/clay nanocomposites had the close porosity to that of clay. Tuning the Cu2+/PEI ratio in PEI−Cu2+ complex allowed to control CuOx states (loadings, particle sizes, etc.). Tuning of the supporting conditions allowed constructing a structure suitable for CO2 uptake. These findings will contribute to the development of the material science of metal oxide nanoparticles and their hybrid materials in diverse fields including CO2 adsorbents, energy devices, and catalysts. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0020-7136 154 1 2023 Low frequency of intracranial progression in advanced NSCLC patients treated with cancer immunotherapies 169 179 EN Naoya Kemmotsu Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kiichiro Ninomiya Department of Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kei Kunimasa Department of Thoracic Oncology, Osaka International Cancer Institute Takamasa Ishino Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Joji Nagasaki Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihiro Otani Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Michiue Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eiki Ichihara Department of Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kadoaki Ohashi Department of Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takako Inoue Department of Thoracic Oncology, Osaka International Cancer Institute Motohiro Tamiya Department of Thoracic Oncology, Osaka International Cancer Institute Kazuko Sakai Department of Genome Biology, Kindai University Faculty of Medicine Youki Ueda Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiromichi Dansako Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuto Nishio Department of Genome Biology, Kindai University Faculty of Medicine Katsuyuki Kiura Department of Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Isao Date Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yosuke Togashi Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Intracranial metastases are common in nonsmall-cell lung cancer (NSCLC) patients, whose prognosis is very poor. In addition, intracranial progression is common during systemic treatments due to the inability to penetrate central nervous system (CNS) barriers, whereas the intracranial effects of cancer immunotherapies remain unclear. We analyzed clinical data to evaluate the frequency of intracranial progression in advanced NSCLC patients treated with PD-1 blockade therapies compared with those treated without PD-1 blockade therapies, and found that the frequency of intracranial progression in advanced NSCLC patients treated with PD-1 blockade therapies was significantly lower than that in patients treated with cytotoxic chemotherapies. In murine models, intracranial rechallenged tumors after initial rejection by PD-1 blockade were suppressed. Accordingly, long-lived memory precursor effector T cells and antigen-specific T cells were increased by PD-1 blockade in intracranial lesions. However, intracranial rechallenged different tumors are not suppressed. Our results indicate that cancer immunotherapies can prevent intracranial progression, maintaining long-term effects intracranially as well as systemically. If intracranial recurrence occurs during the treatment with PD-1 blockade therapies, aggressive local therapies could be worthwhile. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0021-5155 67 6 2023 Accuracy of ultrasound vs. Fourier-domain optic biometry for measuring preoperative axial length in cases of rhegmatogenous retinal detachment 645 651 EN Shuhei Kimura Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mio Morizane Hosokawa Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Shiode Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryo Matoba Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Kanzaki Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuhito Goto Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Kanenaga Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Etsuji Suzuki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Morizane Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose To identify a method for accurately measuring preoperative axial length (AL) in cases of rhegmatogenous retinal detachment (RRD).<br> Study design Retrospective study.<br> Methods This retrospective study included 83 eyes of 83 patients who underwent vitrectomy for RRD and had both preoperative and postoperative data for AL. Preoperative AL measurements for the affected eye were obtained using ultrasound (aUS-AL) and compared with those for affected and fellow eyes measured using optical biometry (aOB-AL and fOB-AL, respectively). Absolute differences between preoperative aUS-AL, aOB-AL, or fOB-AL measurements and postoperative AL (aPost-AL) were examined.<br> Results In the 41 eyes without macular detachment, the absolute difference between aOB-AL and aPost-AL (0.06±0.07 mm) was significantly smaller than between aUS-AL and aPost-AL (0.21±0.18 mm) and that between fOB-AL and aPost-AL (0.29±0.35 mm) (P = 0.017 and P < 0.001, respectively). In the 42 eyes with macular detachment, the absolute difference between aOB-AL and aPost-AL (1.22±2.40 mm) was significantly larger than between aUS-AL and aPost-AL (0.24±0.24 mm) and between fOB-AL and aPost-AL (0.35±0.49 mm) (P = 0.006, P = 0.016, respectively).<br> Conclusion The current findings suggest that aOB-AL is more accurate than aUS-AL or fOB-AL in cases of RRD without macular detachment, while aUS-AL or fOB-AL is more accurate than aOB-AL in cases with macular detachment. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0953-8194 35 9 2023 Neuropeptidergic control circuits in the spinal cord for male sexual behaviour: Oxytocin–gastrin‐releasing peptide systems e13324 EN Takumi Oti Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University Hirotaka Sakamoto Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University The neuropeptidergic mechanisms controlling socio-sexual behaviours consist of complex neuronal circuitry systems in widely distributed areas of the brain and spinal cord. At the organismal level, it is now becoming clear that “hormonal regulations” play an important role, in addition to the activation of neuronal circuits. The gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord is an important component of the neural circuits that control penile reflexes in rats, circuits that are commonly referred to as the “spinal ejaculation generator (SEG).” Oxytocin, long known as a neurohypophyseal hormone, is now known to be involved in the regulation of socio-sexual behaviors in mammals, ranging from social bonding to empathy. However, the functional interaction between the SEG neurons and the hypothalamo-spinal oxytocin system remains unclear. Oxytocin is known to be synthesised mainly in hypothalamic neurons and released from the posterior pituitary into the circulation. Oxytocin is also released from the dendrites of the neurons into the hypothalamus where they have important roles in social behaviours via non-synaptic volume transmission. Because the most familiar functions of oxytocin are to regulate female reproductive functions including parturition, milk ejection, and maternal behaviour, oxytocin is often thought of as a “feminine” hormone. However, there is evidence that a group of parvocellular oxytocin neurons project to the lower spinal cord and control male sexual function in rats. In this report, we review the functional interaction between the SEG neurons and the hypothalamo-spinal oxytocin system and effects of these neuropeptides on male sexual behaviour. Furthermore, we discuss the finding of a recently identified, localised “volume transmission” role of oxytocin in the spinal cord. Findings from our studies suggest that the newly discovered “oxytocin-mediated spinal control of male sexual function” may be useful in the treatment of erectile and ejaculatory dysfunction. No potential conflict of interest relevant to this article was reported.

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

American Chemical Society (ACS) Acta Medica Okayama 0022-3263 88 14 2023 Oxytrofalcatin Puzzle: Total Synthesis and Structural Revision of Oxytrofalcatins B and C 9920 9926 EN Kazuma Sugitate Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiki Yamashiro Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ibuki Takahashi Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-tobetsu, Hokkaido 0610293, Japan Koji Yamada Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The previously reported structures of oxytrofalcatins B and C possess a benzoyl indole core. However, following synthesis and NMR comparison of both the proposed structure and the synthesized oxazole, we have revised the structure of oxytrofalcatins B and C as oxazoles. The synthetic route developed herein can further our understanding of the biosynthetic pathways that govern the production of natural 2,5-diaryloxazoles. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 0304-8608 167 12 2022 Identification of novel totiviruses from the ascomycetous fungus Geotrichum candidum 2833 2838 EN Haris Ahmed Khan Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST) Hideki Kondo Institute of Plant Science and Resources (IPSR), Okayama University Sabitree Shahi Institute of Plant Science and Resources (IPSR), Okayama University Muhammad Faraz Bhatti Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST) Nobuhiro Suzuki Institute of Plant Science and Resources (IPSR), Okayama University Mycoviruses are widely distributed across the kingdom Fungi, including ascomycetous yeast strains of the class Saccharomycetes. Geotrichum candidum is an important fungal pathogen belonging to Saccharomycetes and has a diverse host range. Here, we report the characterization of four new classical totiviruses from two distinct Geotrichum candidum strains from Pakistan. The four identified viruses were tentatively named “Geotrichum candidum totivirus 1, 2, 3a, and 3b” (GcTV1-3b). The complete dsRNA genomes of the identified totiviruses are 4621, 4592, 4576, and 4576 bp in length, respectively. All totivirus genomes have two open reading frames, encoding a capsid protein (CP) and an RNA-dependent RNA polymerase (RdRP), respectively. The downstream RdRP domain is assumed to be expressed as a CP-RdRP fusion product via -1 frameshifting mediated by a heptameric slippery site. Sequence comparisons and phylogenetic analysis showed that each of the discovered viruses belongs to a new species of the genus Totivirus in the family Totiviridae, with GcTV1 and GcTV3 (a and b strains) clustering in one subgroup and GcTV2 in another subgroup. No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 1438-4957 25 4 2023 Sequential flotation of 4 components in silicon-based waste solar cells 2407 2416 EN Mami Mizukawa Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Noriko Nishimura Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Md. Azhar Uddin Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Yoshiei Kato Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Yu-ichi Uchida Department of Applied Chemistry, Faculty of Fundamental Engineering, Nippon Institute of Technology Si, Al, Cu, and Ag particles’ mixture which mainly composes pulverized silicon-based waste solar cells were individually separated by the batch flotation experiments with high recovery and content, and then a general flow chart of the sequential flotation procedure of n-component was postulated including 2-, 3-, and 4-components. The n-component mixture was separated to 1: n-1 or i: j (i + j = n) by a flotation procedure and n-1 times operation was necessary to divide into the individual component. The first flotation process to separate Al into the froth layer was carried out with a collector of SDS solution after dipping Si, Al, Cu, and Ag mixture into the SDS solution. Si was separated in the froth by the second flotation with a collector of a commercial neutral detergent after Al etching by HCl, and Si, Cu and Ag mixture dipped in the detergent. The Cu and Ag mixture was calcinated at 673 or 773 K and dipped into the detergent, and the third flotation with the collector of the detergent led to Cu in the froth and Ag in the sediment. The 4-component mixture was successfully separated into each component by the 3-consecutive flotation processes. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Prognostic Utility of the Glasgow Prognostic Score for the Long-Term Outcomes After Liver Resection for Intrahepatic Cholangiocarcinoma: A Multi-institutional Study EN Kenta SUI 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 Low incidence of restenosis after successful balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension EN Isao TABUCHI 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 Suramin prevents the development of diabetic kidney disease by inhibiting NLRP3 inflammasome activation in KK-Ay mice EN Kaori ODA 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 Correlation between renal ablation zone in contrast-enhanced CT and non-enhanced MRI during the early period following percutaneous cryoablation EN Noriyuki UMAKOSHI 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 Differences in extracellular fluid volume between acute heart failure patients with and without high systolic blood pressure EN Yusuke NAMBA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2513-0390 6 7 2023 Particle and Heavy Ion Transport Code System‐Based Microdosimetry for the Development of Boron Agents for Boron Neutron Capture Therapy 2300163 EN Takafumi Shigehira Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Hanafusa Neutron Therapy Research Center, Okayama University Kazuyo Igawa Neutron Therapy Research Center, Okayama University Tomonari Kasai Neutron Therapy Research Center, Okayama University Shuichi Furuya Research Laboratory of Accelerator-Based BNCT system, Graduate School of Engineering Nagoya University Hisakazu Nishimori Department of Hematology and Oncology Okayama University Hospital Okayama Okayama 700–8558 Japan Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Hiroyuki Michiue Neutron Therapy Research Center, Okayama University Atsushi Fujimura Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Boron neutron capture therapy (BNCT) is a radiation therapy that selectively kills cancer cells at the cellular level using the boron neutron capture reaction (BNCR) (10B(n.α)7Li). The amount of boron 10B delivers in boronophenylalanine (BPA)-BNCT to achieve anti-tumor effects is ≈15–40 ppm. The same is true for all boron drugs; however, whether the same amount of 10B is required for other boron drugs with different accumulation characteristics has not been intensively investigated. Therefore, herein, a virtual cell model with intracellular organelles is prepared, and the BPA equivalent dose concentration to the cell nucleus is analyzed using particle and heavy ion transport code system-based microdosimetry. Additionally, the intranuclear minimal region (IMR) is set as a reference for the concept of the intranuclear domain in the microdosimetric kinetic model, and the BPA equivalent dose concentration to the IMR is estimated. The required boron delivery dose greatly varies depending on the dose assessment based on the accumulation characteristics of boron agents in intracellular organelles. Evaluation of the BNCR effect according to the accumulation characteristics without being influenced by the specified value of 15–40 ppm is recommended. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1438-4957 25 2 2022 Flotation kinetics of aluminum powders derived from waste crystalline silicon solar cells and its comparison between batch, continuous and column flotation practices 826 834 EN Yoshiei Kato Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Sho Harada Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Noriko Nishimura Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Md. Azhar Uddin Department of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Yu-ichi Uchida Department of Applied Chemistry, Faculty of Fundamental Engineering, Nippon Institute of Technology In this study, floatability rate of aluminum (Al) powders was analyzed for the purpose of separating valuable resources from residual materials in waste photovoltaic (PV) solar cells, and equations for flotation recovery were developed for various flotation types according to the rate-determining steps of the gas flowrate and feed rate. The flotation rate became a zero-order reaction at the rate-determining step of the gas flow rate and had the same form between a batch and continuous typed practices by substituting residence time with real time. Under the rate-determining step of the feed rate, the flotation rate was expressed by the linear combination of the first-order reaction of an even group material. The flotation recovery rate of Al powders was analyzed by the data of a batch floatability experiment and indicated by the linear expression of the first-order reaction of two groups due to the rate-determining step of the feed rate. The calculated separation recovery of n-cell type device increased as the number of cells increased and approached that of the batch and column types. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1472-4782 22 4 2023 Unraveling the stagnation of employee pay in Japanese firms: the impact of profit creation, employee productivity, and employee share 1743 1772 EN Yuanyuan Gong Discovery Program for Global Learners, Okayama University Shige Makino Graduate School of Economics, Kyoto University Aqi Liu Industrial Development Department, China Merchants Group Limited Huanchen Liu Department of Business Administration, Nanjing University of Aeronautics and Astronautics Jingyi Wang UNSW Business School, University of New South Wales This study investigated the causes of stagnant employee pay in Japanese firms. By analyzing agency theory and Japanese governance structure, we argue that pay levels are affected by profit creation, employee productivity, and employee share. Dysfunctional processes in these areas can result in pay stagnation. Our findings demonstrate that employee productivity and profit creation have equally significant impacts on pay levels, whereas employee share affects pay only with high employee productivity. These results suggest that the main reason for stagnant employee pay in Japan is not a failure of profit sharing but rather a failure to link corporate and employee capabilities to a firm’s earning power. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0021-5155 67 4 2023 A factor for predicting simultaneous internal limiting membrane peeling during epiretinal membrane removal: swept-source optical coherence tomography-based evaluation of epiretinal membrane adhesion to the retina 410 416 EN Ryo Matoba Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Kanzaki Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shuhei Kimura Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mio M. Hosokawa Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Shiode Tetsuro Morita Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Morizane Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose　To investigate preoperative factors associated with simultaneous internal limiting membrane (ILM) peeling during epiretinal membrane (ERM) removal.<br> Study design　Observational cross-sectional study.<br> Methods　We retrospectively reviewed 60 eyes with idiopathic ERM that underwent vitrectomy. The gap between the ERM and ILM was visualized using en face optical coherence tomography. The depth and width of the ERM–ILM gap at the initiation site of ERM removal were measured, and the relationship between preoperative factors including these parameters and simultaneous ILM peeling during ERM removal was investigated.<br> Results　The ILM was simultaneously peeled during ERM removal in 30 eyes, but not in the other 30 eyes. Age was significantly higher (P = 0.017) and the width of the ERM–ILM gap was significantly smaller (P < 0.001) in the simultaneous ILM peeling (+) group than in the simultaneous ILM peeling (–) group. Multivariate logistic regression analysis confirmed the width of the ERM–ILM gap as a significant negative predictor for simultaneous ILM peeling (odds ratio, 0.992; 95% confidence interval, 0.986–0.997; P = 0.003). Receiver operating characteristic curve analysis of the width of the ERM–ILM gap revealed that the optimal cutoff for predicting simultaneous ILM peeling was 187.1 µm.<br> Conclusion　The small width of the ERM–ILM gap at the initiation site of ERM removal was significantly associated with simultaneous ILM peeling, indicating that the adhesion strength between the ERM and ILM at the initial ERM grasping site determines whether simultaneous ILM peeling will occur during ERM removal. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0195-928X 44 5 2023 Synthesis and Characterization of Silica-Encapsulated n-Tetracosane and the Effect of Surface Modification by Silane Coupling Agents 69 EN Kyosuke Okuno Graduate School of Natural Science and Technology, Okayama University Kazuma Isobe Graduate School of Natural Science and Technology, Okayama University Akihiko Horibe Graduate School of Natural Science and Technology, Okayama University Yutaka Yamada Graduate School of Natural Science and Technology, Okayama University Microencapsulation of n-tetracosane, whose melting point is approximately 50 degrees C, in a silica shell has been performed through the sol-gel method using tetraethyl orthosilicate (TEOS) as the precursor for silica-shell formation. Additionally, two types of silane coupling agents were used to modify the surface of the microcapsules to change the wettability. The morphology of the microcapsules was observed by scanning electron microscopy. The chemical composition was characterized by Fourier transform infrared spectroscopy. The results confirmed the presence of n-tetracosane and silica in the synthesized microcapsules. Wettability analysis showed hydrophobic and hydrophilic features because of the added silane coupling agents. From the results of differential scanning calorimetry measurements, the encapsulation ratio of the microcapsules increased with decreasing TEOS/n-tetracosane ratio, and the highest encapsulation ratio was 87.1 % at a TEOS/n-tetracosane ratio of 0.25. The pH in the microcapsule solution was affected by addition of a silane coupling agent, and shifting the pH to the basic side lowered the encapsulation ratio owing to enhancement of silica condensation. After 100 differential scanning calorimetry cycles, there was no significant degradation in the phase-change temperatures and enthalpies, which confirmed the good phase-change stability and repeatability. Therefore, the microcapsules are a potential material for thermal-energy-storage systems to effectively utilize energy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 2 2023 Personalized Preclinical Training in Dental Ergonomics and Endodontics in Undergraduate Dentistry Students (Pilot Study) 147 159 EN Zulema Arias Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Stephanie Haines Department of Health Tadashi Yamamoto Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kazu Hatanaka Department of Periodontics and Endodontics, Okayama University Hospital Keisuke Yamashiro Department of Periodontics and Endodontics, Okayama University Hospital Norihiro Sonoi Department of Periodontics and Endodontics, Okayama University Hospital Shogo Takashiba Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65144 The curriculum at the Department of Pathophysiology in the Periodontal Sciences program at Okayama University includes normative preclinical training (NPT) using phantoms. NPT is given to the whole class of 5 th year students divided in groups of 8 students/instructor. In 2019, an innovative personalized preclinical training (PPT) pilot study was implemented for this group of students whereby two students, each with their own dental unit, were coached by one instructor. The main topics covered were dental ergonomics and endodontics. We aimed to evaluate the effectiveness of PPT in dental ergonomics and endodontics toward increasing the knowledge and future clinical skills of students who had already undergone NPT. A test on endodontics was taken before and after PPT. A questionnaire was completed to assess their perception of improvement regarding the above-mentioned topics. Test scores and questionnaire results both showed that the students’ level of knowledge and awareness of future clinical skills was significantly higher after PPT. This pilot study demonstrated that PPT increased the students’ knowledge and future clinical skills. As preclinical training forms the foundation for clinical practice, investment in future research regarding this personalized approach is likely to enhance students’ understanding and clinical performance. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1633-8065 32 2 2021 A posterior shiny-corner lesion of the tibia is observed in the early phase after medial meniscus posterior root tear 301 306 EN Yuki Okazaki Department of Orthopaedic Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takayuki Furumatsu Department of Orthopaedic Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuya Kajiki Department of Orthopaedic Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takaaki Hiranaka Department of Orthopaedic Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Keisuke Kintaka Department of Orthopaedic Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuya Kodama Department of Orthopaedic Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yusuke Kamatsuki Department of Orthopaedic Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshifumi Ozaki Department of Orthopaedic Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Backgrounds<br> Medial meniscus (MM) posterior root tear (PRT) results in joint overloading and degenerative changes in the knee, and pullout repair is recommended to prevent subsequent osteoarthritis. Diagnosing MMPRT is sometimes difficult, especially in the case of an incomplete tear. A posterior shiny-corner lesion (PSCL) is reported to be useful for diagnosis, although the association between MMPRT and PSCL is unknown. This study aimed to investigate the properties of PSCL, such as the location, volume, and duration from injury to the time of MRI (duration). We hypothesized that PSCL is observed in the early phase after the MMPRT onset.<br><br> Methods<br> T2-weighted fat-suppression magnetic resonance imaging (MRI) was obtained from 55 patients with MMPRT preoperatively. The prevalence of the PSCL; giraffe neck, cleft, and ghost signs; severe MM extrusion (> 3 mm); and the PSCL volume were evaluated. The PSCL lesion elliptical volume (mm3) was calculated by measuring the anteroposterior, transverse, and craniocaudal dimensions.<br> <br><br> Results<br> PSCL was observed in 34 (62%) cases. The mean volume of the PSCL was 102.0 mm3. A significantly shorter duration was observed in the PSCL-positive group (5.6 weeks) than that in the PSCL-negative group (40.9 weeks, P < 0.01), although no significant correlation was observed between the PSCL volume and duration. The sensitivity for the MMPRT was 90.5% when the cut-off duration value was 3 weeks and 81.8% when the cut-off value was 8 weeks.<br><br> Conclusions<br> MRI examination may detect PSCL if it is performed early following MMPRT onset. Detecting PSCL may be useful in diagnosing MMPRT with high sensitivity. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1873-9601 17 2 2023 Do not overwork: cellular communication network factor 3 for life in cartilage 353 359 EN Satoshi Kubota Department of Biochemistry and Molecular Dentistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Harumi Kawaki Department of Oral Biochemistry, Asahi University School of Dentistry Bernard Perbal International CCN Society Masaharu Takigawa Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences/Dental School Kazumi Kawata Department of Biochemistry and Molecular Dentistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Takako Hattori Department of Biochemistry and Molecular Dentistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Takashi Nishida Department of Biochemistry and Molecular Dentistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Cellular communication network factor (CCN) 3, which is one of the founding members of the CCN family, displays diverse functions. However, this protein generally represses the proliferation of a variety of cells. Along with skeletal development, CCN3 is produced in cartilaginous anlagen, growth plate cartilage and epiphysial cartilage. Interestingly, CCN3 is drastically induced in the growth plates of mice lacking CCN2, which promotes endochondral ossification. Notably, chondrocytes in these mutant mice with elevated CCN3 production also suffer from impaired glycolysis and energy metabolism, suggesting a critical role of CCN3 in cartilage metabolism. Recently, CCN3 was found to be strongly induced by impaired glycolysis, and in our study, we located an enhancer that mediated CCN3 regulation via starvation. Subsequent investigations specified regulatory factor binding to the X-box 1 (RFX1) as a transcription factor mediating this CCN3 regulation. Impaired glycolysis is a serious problem, resulting in an energy shortage in cartilage without vasculature. CCN3 produced under such starved conditions restricts energy consumption by repressing cell proliferation, leading chondrocytes to quiescence and survival. This CCN3 regulatory system is indicated to play an important role in articular cartilage maintenance, as well as in skeletal development. Furthermore, CCN3 continues to regulate cartilage metabolism even during the aging process, probably utilizing this regulatory system. Altogether, CCN3 seems to prevent "overwork" by chondrocytes to ensure their sustainable life in cartilage by sensing energy metabolism. Similar roles are suspected to exist in relation to systemic metabolism, since CCN3 is found in the bloodstream. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4426 13 1 2022 Reliability of the Garden Alignment Index and Valgus Tilt Measurement for Nondisplaced Femoral Neck Fractures 53 EN Yasuaki Yamakawa Department of Orthopedic Surgery, Kochi Health Sciences Center Norio Yamamoto Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yosuke Tomita Department of Physical Therapy, Faculty of Health Care, Takasaki University of Health and Welfare Ryuichiro Okuda Department of Orthopedic Surgery, Kochi Health Sciences Center Yasutaka Masada Department of Orthopedic Surgery, Kochi Health Sciences Center Akihiro Shiroshita Scientific Research Works Peer Support Group (SRWS-PSG) Toshiyuki Matsumoto Department of Orthopedic Surgery, Kochi Health Sciences Center Anteroposterior (AP) alignment assessment for nondisplaced femoral neck fractures is important for determining the treatment strategy and predicting postoperative outcomes. AP alignment is generally measured using the Garden alignment index (GAI). However, its reliability remains unknown. We compared the reliability of GAI and a new AP alignment measurement (valgus tilt measurement [VTM]) using preoperative AP radiographs of nondisplaced femoral neck fractures. The study was designed as an intra- and inter-rater reliability analysis. The raters were four trauma surgeons who assessed 50 images twice. The main outcome was the intraclass correlation coefficient (ICC). To calculate intra- and inter-rater reliability, we used a mixed-effects model considering rater, patient, and time. The overall ICC (95% CI) of GAI and VTM for intra-rater reliability was 0.92 (0.89-0.94) and 0.86 (0.82-0.89), respectively. The overall ICC of GAI and VTM for inter-rater reliability was 0.92 (0.89-0.95), and 0.85 (0.81-0.88), respectively. The intra- and inter-rater reliability of GAI was higher in patients aged <80 years than in patients aged >= 80 years. Our results showed that GAI is a more reliable measurement method than VTM, although both are reliable. Variations in patient age should be considered in GAI measurements. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0300-8177 478 8 2022 Significance of UGT1A6, UGT1A9, and UGT2B7 genetic variants and their mRNA expression in the clinical outcome of renal cell carcinoma 1779 1790 EN Jun Matsumoto Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Anzu Nishimoto Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Watari Department of Urology, National Hospital Organization Okayama Medical Center Hideo Ueki Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Shoya Shiromizu Department of Pharmacy, Okayama University Hospital Naohiro Iwata Department of Pharmacy, Okayama University Hospital Tatsuaki Takeda Department of Pharmacy, Okayama University Hospital Soichiro Ushio Department of Pharmacy, Okayama University Hospital Makoto Kajizono Department of Pharmacy, Okayama University Hospital Masachika Fujiyoshi Department of Pharmacy, Tottori University Hospital Toshihiro Koyama Department of Pharmaceuticals Biomedicine, 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 Koichiro Wada Department of Urology, Faculty of Medicine, Shimane University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Yasutomo Nasu Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Noritaka Ariyoshi Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University UDP-glucuronosyltransferase (UGT) metabolizes a number of endogenous and exogenous substrates. Renal cells express high amounts of UGT; however, the significance of UGT in patients with renal cell carcinoma (RCC) remains unknown. In this study, we profile the mRNA expression of UGT subtypes (UGT1A6, UGT1A9, and UGT2B7) and their genetic variants in the kidney tissue of 125 Japanese patients with RCC (Okayama University Hospital, Japan). In addition, we elucidate the association between the UGT variants and UGT mRNA expression levels and clinical outcomes in these patients. The three representative genetic variants, namely, UGT1A6 541A > G, UGT1A9 i399C > T, and UGT2B7-161C > T, were genotyped, and their mRNA expression levels in each tissue were determined. We found that the mRNA expression of the three UGTs (UGT1A6, UGT1A9, and UGT2B7) are significantly downregulated in RCC tissues. Moreover, in patients with RCC, the UGT2B7-161C > T variant and high UGT2B7 mRNA expression are significantly correlated with preferable cancer-specific survival (CSS) and overall survival (OS), respectively. As such, the UGT2B7-161C > T variant and UGT2B7 mRNA expression level were identified as significant independent prognostic factors of CSS and CSS/OS, respectively. Taken together, these findings indicate that UGT2B7 has a role in RCC progression and may, therefore, represent a potential prognostic biomarker for patients with RCC. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0341-2695 47 10 2022 Concomitant posterior anchoring further reduces posterior meniscal extrusion during pullout repair of medial meniscus posterior root tears: a retrospective study 2391 2400 EN Haowei Xue Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Takayuki Furumatsu Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Takaaki Hiranaka Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Keisuke Kintaka Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Naohiro Higashihara Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Masanori Tamura Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Ximing Zhang Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Purpose<br> Transtibial pullout repair improves the clinical outcomes of medial meniscus (MM) posterior root tears (PRTs); however, reducing MM extrusion remains challenging. Thus, the purpose of this study was to examine the role of additional posterior anchoring (PA) during pullout repair in reducing the severity of MM extrusion compared to pullout repair alone. <br><br> Methods<br> Patients who underwent pullout repair with two-cinch stitches (TCS) only or TCS combined with PA (TCSPA)-deployment of an additional suture anchor in the posteromedial corner of MM-were included retrospectively. MM medial and posterior extrusion (MMME and MMPE), MM extrusion and remaining volume (MMEV and MMRV), and corresponding ratios were evaluated pre-operatively and three months post-operatively using a three-dimensional meniscal model at 10 degrees and 90 degrees of knee flexion and compared within and between groups. <br><br> Results<br> A total of 15 and 16 patients treated with TCS and TCS-PA, respectively, were enrolled. At 90 degrees knee flexion, both techniques significantly reduced MMPE (TCS: 4.2 +/- 0.7 mm to 3.5 +/- 0.6 mm, p < 0.05; TCS-PA: 3.7 +/- 0.8 mm to 2.8 +/- 0.7 mm, p < 0.05) at three months post-operatively. TCS-PA reduced MMPE more significantly than TCS alone (p < 0.05). Only TCS-PA significantly improved the MMEV and MMRV ratios (39.6 +/- 8.9% to 28.1 +/- 6.0%, p < 0.05 and 60.4 +/- 8.9% to 71.9 +/- 6.0%, p < 0.05, respectively). Significance was not found in all other comparisons. <br><br> Conclusions<br> Both techniques improved MMPE at knee flexion at the three month follow-up, with TCS-PA providing significantly superior results. Our findings support the evidence that the application of PA may be an effective surgical option for alleviating persistent MMPE. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0942-2056 31 6 2022 The clinical and radiographic outcomes of type 2 medial meniscus posterior root tears following transtibial pullout repair 2323 2330 EN Takaaki Hiranaka Department of Orthopaedic Surgery, Okayama University Hospital Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Hospital Yusuke Yokoyama Department of Orthopaedic Surgery, Okayama University Hospital Keisuke Kintaka Department of Orthopaedic Surgery, Okayama University Hospital Naohiro Higashihara Department of Orthopaedic Surgery, Okayama University Hospital Masanori Tamura Department of Orthopaedic Surgery, Okayama University Hospital Koki Kawada Department of Orthopaedic Surgery, Okayama University Hospital Haowei Xue Department of Orthopaedic Surgery, Okayama University Hospital Masanori Hamada Department of Orthopaedic Surgery, Okayama University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Hospital Purpose The aim of this study was to compare the clinical outcomes of different subtypes of type 2 medial meniscus posterior root tears following transtibial pullout repair. <br> Methods In total, 147 patients (mean age: 66.2 +/- 8.3 years) who were diagnosed with type 2 medial meniscus posterior root tears and underwent transtibial pullout repair were included. Patients were divided into 2A (n = 31), 2B (n = 90), and 2C (n = 26) groups according to tear type. Clinical outcomes were assessed pre-operatively and at second-look arthroscopy using the Knee injury and Osteoarthritis Outcome Score. The meniscal healing status was evaluated at second-look arthroscopy. Medial meniscus extrusion was calculated using magnetic resonance imaging pre-operatively and at second-look arthroscopy. <br> Results No significant differences in pre-operative or post-operative clinical scores were observed between each subtype, although clinical scores improved post-operatively for each subtype. Significant differences were noted in the anteroposterior width of the bridging tissues at second-look arthroscopy (2A, 7.1 +/- 1.2; 2B, 6.2 +/- 1.7; and 2C, 6.2 +/- 1.7 mm; p = 0.045); type 2A tears were the widest. There was a significant difference in post-operative medial meniscus extrusion (2A, 3.2 +/- 0.9; 2B, 4.0 +/- 1.2; and 2C, 4.0 +/- 1.4 mm; p = 0.004) and its progression (2A, 0.7 +/- 0.6; 2B, 1.2 +/- 0.8; and 2C, 1.2 +/- 0.8 mm; p= 0.008), and type 2A tears were the shortest. <br> Conclusion Although there was no significant difference in the post-operative clinical scores among different type 2 tears in the short term, type 2A tears showed better healing and medial meniscus extrusion progression prevention, thus indicating the usefulness of classifying tear type in estimating post-operative outcomes. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1433-5298 28 1 2022 Growing neural gas based navigation system in unknown terrain environment for an autonomous mobile robot 76 88 EN Yuichiro Toda Graduate school of natural science and technology, Okayama University Koki Ozasa Graduate school of natural science and technology, Okayama University Takayuki Matsuno Graduate school of natural science and technology, Okayama University Recently, various types of autonomous robots have been expected in many fields such as a disaster site, forest, and so on. The autonomous robots are assumed to be utilized in unknown environments. In such environments, a path planning to a target point set in the unknown area is a fundamental capability for efficiently executing tasks. To realize the 3D space perception, GNG with Different Topologies (GNG-DT) proposed in our previous work can learn the multiple topological structures with in the framework of learning algorithm. This paper proposes a GNG-DT based 3D perception method by utilizing the multiple topological structures for perceiving the 3D unknown terrain environment and a path planning method to the target point set in the unknown area. Especially, a traversability property of the robot is added to GNG-DT as a new property of the topological structures for clustering the 3D terrain environment from the 3D point cloud measured by 3D Lidar. Furthermore, this paper proposes a path planning method utilizing the multiple topological structures. Next, this paper shows several experimental results of the proposed method using simulation terrain environments for verifying the effectiveness of our proposed method. Finally, we summarize our proposed method and discuss the future direction on this research. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0915-5635 35 4 2022 Endoscopic ablation therapy for the pancreatic neoplasms 430 442 EN Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Hospital Recently, endoscopic ultrasound (EUS)-guided ablation therapy has been reported as a less invasive therapy for patients with pancreatic neoplasms. Some ablation techniques, including injective ablation (using ethanol or other ablative agents), radiofrequency ablation (RFA), photodynamic therapy, and laser ablation, have been described in the literature. Among these, injective ablation and RFA are more frequently used for treating pancreatic neoplasms. Few studies have evaluated the effectiveness of EUS-guided ethanol ablation (EUS-EA) for potentially malignant solid neoplasms (neuroendocrine neoplasms or solid pseudopapillary neoplasms) and have reported a complete response (CR) rate of 60-80%. In addition, the CR rate after EUS-RFA for these lesions has been reported to be 55-100%, with no additional procedure-related adverse events (AEs). Regarding the amelioration of the symptoms of an insulinoma, the success rates of both the therapies were found to be excellent. Regarding complete tumor ablation, EUS-RFA appeared to be superior to EUS-EA. Although EUS-RFA has been reported as a safe treatment for pancreatic cancers, its effectiveness remains inadequate. Some studies have examined the effectiveness of EUS-guided injection ablation therapy for pancreatic cystic neoplasms (PCNs) and have reported CR rates that range from 35% to 79%. Alcohol-free chemotherapeutic agent ablation appears to be effective, with a low risk of AEs. However, studies on the effectiveness of EUS-RFA for PCNs are limited. In the future, EUS-guided ablation therapy could become a more widely used approach for potentially malignant and malignant pancreatic lesions. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0022-0957 74 3 2022 The secreted immune response peptide 1 functions as a phytocytokine in rice immunity 1059 1073 EN Pingyu Wang Key Laboratory of Plant Hormones and Development Regulation of Chongqing, School of Life Sciences, Chongqing University Huimin Jia Shanghai Center for Plant Stress Biology and Center of Excellence for Molecular Plant Sciences, Chinese Academy of Sciences Ting Guo Shanghai Center for Plant Stress Biology and Center of Excellence for Molecular Plant Sciences, Chinese Academy of Sciences Yuanyuan Zhang Shanghai Center for Plant Stress Biology and Center of Excellence for Molecular Plant Sciences, Chinese Academy of Sciences Wanqing Wang Institute of Plant Science and Resources, Okayama University Hideki Nishimura Institute of Plant Science and Resources, Okayama University Zhengguo Li Key Laboratory of Plant Hormones and Development Regulation of Chongqing, School of Life Sciences, Chongqing University Yoji Kawano Shanghai Center for Plant Stress Biology and Center of Excellence for Molecular Plant Sciences, Chinese Academy of Sciences Small signalling peptides play important roles in various plant processes, but information regarding their involvement in plant immunity is limited. We previously identified a novel small secreted protein in rice, called immune response peptide 1 (IRP1). Here, we studied the function of IRP1 in rice immunity. Rice plants overexpressing IRP1 enhanced resistance to the virulent rice blast fungus. Application of synthetic IRP1 to rice suspension cells triggered the expression of IRP1 itself and the defence gene phenylalanine ammonia-lyase 1 (PAL1). RNA-seq results revealed that 84% of genes up-regulated by IRP1, including 13 OsWRKY transcription factors, were also induced by a microbe-associated molecular pattern (MAMP), chitin, indicating that IRP1 and chitin share a similar signalling pathway. Co-treatment with chitin and IRP1 elevated the expression level of PAL1 and OsWRKYs in an additive manner. The increased chitin concentration arrested the induction of IRP1 and PAL1 expression by IRP1, but did not affect IRP1-triggered mitogen-activated protein kinases (MAPKs) activation. Collectively, our findings indicate that IRP1 functions as a phytocytokine in rice immunity regulating MAPKs and OsWRKYs that can amplify chitin and other signalling pathways, and provide new insights into how MAMPs and phytocytokines cooperatively regulate rice immunity. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0906-6705 32 3 2022 Resistance to immune checkpoint inhibitors and the tumor microenvironment 240 249 EN Shusuke Kawashima Department of Dermatology, Graduate School of Medicine, Chiba University Yosuke Togashi Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Immune checkpoint inhibitors (ICIs) have contributed significantly to the treatment of various types of cancer, including skin cancer. However, not all patients respond; some patients do not respond at all (primary resistance), while others experience recurrence after the initial response (acquired resistance). Therefore, overcoming ICI resistance is an urgent priority. Numerous ICI resistance mechanisms have been reported. They are seemingly quite complex, varying from patient to patient. However, most involve T cell activation processes, especially in the tumor microenvironment (TME). ICIs exert their effects in the TME by reactivating suppressed T cells through inhibition of immune checkpoint molecules, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Thus, this review focuses on the resistance mechanisms based on the T cell activation process. Here, we classify the main mechanisms of ICI resistance into three categories based on: (1) antigen recognition, (2) T cell migration and infiltration, and (3) effector functions of T cells. By identifying and understanding these resistance mechanisms individually, including unknown mechanisms, we seek to contribute to the development of novel treatments to overcome ICI resistance. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0340-7004 72 5 2022 Oncolytic virus-mediated reducing of myeloid-derived suppressor cells enhances the efficacy of PD-L1 blockade in gemcitabine-resistant pancreatic cancer 1285 1300 EN Yoshinori Kajiwara 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 Motohiko Yamada 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 Takuro Fushimi 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 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) is often refractory to treatment with gemcitabine (GEM) and immune checkpoint inhibitors including anti-programmed cell death ligand 1 (PD-L1) antibody. However, the precise relationship between GEM-resistant PDAC and development of an immunosuppressive tumor microenvironment (TME) remains unclear. In this study, we investigated the immunosuppressive TME in parental and GEM-resistant PDAC tumors and assessed the therapeutic potential of combination therapy with the telomerase-specific replication-competent oncolytic adenovirus OBP-702, which induces tumor suppressor p53 protein and PD-L1 blockade against GEM-resistant PDAC tumors. Mouse PDAC cells (PAN02) and human PDAC cells (MIA PaCa-2, BxPC-3) were used to establish GEM-resistant PDAC lines. PD-L1 expression and the immunosuppressive TME were analyzed using parental and GEM-resistant PDAC cells. A cytokine array was used to investigate the underlying mechanism of immunosuppressive TME induction by GEM-resistant PAN02 cells. The GEM-resistant PAN02 tumor model was used to evaluate the antitumor effect of combination therapy with OBP-702 and PD-L1 blockade. GEM-resistant PDAC cells exhibited higher PD-L1 expression and produced higher granulocyte-macrophage colony-stimulating factor (GM-CSF) levels compared with parental cells, inducing an immunosuppressive TME and the accumulation of myeloid-derived suppressor cells (MDSCs). OBP-702 significantly inhibited GEM-resistant PAN02 tumor growth by suppressing GM-CSF-mediated MDSC accumulation. Moreover, combination treatment with OBP-702 significantly enhanced the antitumor efficacy of PD-L1 blockade against GEM-resistant PAN02 tumors. The present results suggest that combination therapy involving OBP-702 and PD-L1 blockade is a promising antitumor strategy for treating GEM-resistant PDAC with GM-CSF-induced immunosuppressive TME formation. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1328-8067 64 1 2022 Late‐onset familial Diamond–Blackfan anemia with neutropenia caused by RPL35A variant e15275 EN Kosuke Tamefusa Department of Pediatrics, Okayama University Hospital Michiko Muraoka Department of Pediatrics, Fukuyama City Hospital Kana Washio Department of Pediatrics, Okayama University Hospital Manabu Wakamatsu Department of Pediatrics, Nagoya University Graduate School of Medicine Akira Shimada Department of Pediatrics, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1523-7060 24 42 2022 Total Synthesis of Scabrolide F 7845 7849 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Yuki Sugitani Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Ryohei Morishita Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University The first total synthesis of scabrolide F, a norcembranolide isolated from the soft coral Sinularia scabra, is described. Hydroxycarboxylic acid, which is the key synthetic intermediate, was synthesized in a convergent manner by fragment coupling. The obtained hydroxycarboxylic acid was subjected to macrolactonization and subsequent transannular ring-closing metathesis (RCM) to furnish scabrolide F. The synthetic protocol can be extended to the total synthesis of other norcembranolides. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0910-6340 39 5 2022 Optical collection of extracellular vesicles in a culture medium enhanced by interactions with gold nanoparticles 643 651 EN Yumeki Tani Department of Chemistry, Okayama University Kenta Ochiai Department of Chemistry, Okayama University Takashi Kaneta Department of Chemistry, Okayama University Extracellular vesicles (EVs) exist in biological fluids such as blood, urine, and cerebrospinal fluid and are promising cancer biomarkers. Attempts to isolate and analyze trace EVs, however, have been a challenge for researchers studying their functions and secretion mechanisms, which has stymied the options for diagnostic application. This study demonstrated a collection of EVs that was enhanced by gold nanoparticles (AuNPs) via the use of optical force. The collection system consists of an inverted microscope equipped with a CCD camera, a square capillary connected with a PTFE tube, and an Nd:YAG laser that generates optical force. The laser beam was focused on a capillary wall in which a cell culture medium containing EVs flowed continuously. Control of the surface charges on both the capillary wall and the AuNPs achieved the collection and retention of EVs on the capillary wall. The positively charged capillary wall retained EVs even after the laser irradiation was halted due to the negative charges inherent on the surface of EVs. Conversely, positively charged AuNPs had a strong electrostatic interaction with EVs and enhanced the optical force acting on them, which made collecting them a much more efficient process. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1444-1586 22 12 2022 Trends in the incidence of syphilis in the middle‐aged and older adults in Japan: A nationwide observational study, 2009–2019 1019 1024 EN Misa Takahashi Department of General Medicine Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshihiro Koyama Department of Pharmaceutical Biomedicine Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aim Sexually transmitted infections remain a neglected area of research in geriatrics. However, in the global aging societies, sexual health among the middle-aged and older adults is an emerging public concern. High-income countries are facing a resurgence of syphilis cases among young generations, but little is known about its prevalence in older populations. We aimed to investigate the national trend of syphilis cases in Japan. Methods This nationwide observational study used the publicly-available database (2009-2019) to calculate crude and age-adjusted incidence rates of syphilis per 100 000 population by age, sex and clinical stage. We collected data from patients aged >= 50 years and performed joinpoint regression analysis to estimate long-term trends and average annual percentage changes (AAPCs). Results The total number of patients with syphilis increased about 8-fold from 165 in 2009 to 1280 in 2019. AAPCs of crude incidence rates significantly increased in every age category; 33.2% in 50-59 years, 23.8% in 60-69 years and 20.9% in >= 70 years. Age-adjusted incidence rates have surged at AAPCs of 28.7% in men and 23.1% in women, reaching 4.09 in men and 0.71 in women in 2019. By clinical stage, marked increases were observed in primary (AAPCs, 42.3% in men and 41.6% in women) and secondary syphilis (AAPCs, 24.9% in men and 24.2% in women). Conclusions An up-toward trend of syphilis among people aged >= 50 years was observed. The importance of sexual health among older people should be highlighted in this aging Japanese society. Geriatr Gerontol Int 2022; center dot center dot: center dot center dot-center dot center dot. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 11 1 2022 Novel ABCD1 mutation detected in a symptomatic female carrier of adrenoleukodystrophy 58 60 EN Yumiko Nakano Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Taira Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Sasaki Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koh Tadokoro Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Taijun Yunoki Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Emi Nomura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Fukui Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mami Takemoto Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuta Morihara Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuyuki Shimozawa Division of Genomics Research, Life Science Research Center, Gifu university Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences X-linked adrenoleukodystrophy (ALD) is a major peroxisomal disorder, in which abnormal accumulation of very long-chain fatty acids (VLCFA) caused by ABCD1 gene mutation results in damage to the peripheral and central nervous system and adrenal gland. While affected male patients with ALD present severe neurological symptoms, some female carriers slowly develop spastic gait and urinary incontinence. We report a case of a symptomatic female ALD carrier with a novel ABCD1 gene mutation. She has developed progressive gait disturbance since age 40, and her father and sister had similar symptoms. When admitted to our hospital at age 66, blood analysis showed slight increase of VLCFA, and DNA analysis of ABCD1 gene revealed a novel heterozygous missense mutation (c.1700 A>C, p.Gln567Pro). The genetic testing for ABCD1 gene can be considered in female patients over middle age presenting spastic gait, because female ALD carriers tend to be symptomatic beyond age 60. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1520-6106 126 38 2022 Roles of the Flexible Primary Coordination Sphere of the Mn4CaOx Cluster: What Are the Immediate Decay Products of the S-3 State? 7212 7228 EN Hiroshi Isobe Research Institute for Interdisciplinary Science, Okayama University Mitsuo Shoji Center for Computational Science, University of Tsukuba, Takayoshi Suzuki Research Institute for Interdisciplinary Science, Okayama University Jian-Ren Shen Research Institute for Interdisciplinary Science, Okayama University Kizashi Yamaguchi Institute for NanoScience Design, Osaka University The primary coordination sphere of the multinuclear cofactor (Mn4CaOx) in the oxygen-evolving complex (OEC) of photosystem II is absolutely conserved to maintain its structure and function. Recent time-resolved serial femtosecond crystallography identified large reorganization of the primary coordination sphere in the S-2 to S-3 transition, which elicits a cascade of events involving Mn oxidation and water molecule binding to a putative catalytic Mn site. We examined how the crystallographic fields, created by transient conformational states of the OEC at various time points, affect the thermodynamics of various isomers of the Mn cluster using DFT calculations, with an aim of comprehending the functional roles of the flexible primary coordination sphere in the S-2 to S-3 transition and in the recovery of the S-2 state. The results show that the relative movements of surrounding residues change the size and shape of the cavity of the cluster and thereby affect the thermodynamics of various catalytic intermediates as well as the ability to capture a new water molecule at a coordinatively unsaturated site. The implication of these findings is that the protein dynamics may serve to gate the catalytic reaction efficiently by controlling the sequence of Mn oxidation/reduction and water binding/release. This interpretation is consistent with EPR experiments; g similar to 5 and g similar to 3 signals obtained after near-infrared (NIR) excitation of the S-3 state at 4 K and a g similar to 5 only signal produced after prolonged incubation of the S-3 state at 77 K can be best explained as originating from water-bound S-2 clusters (S-total = 7/2) under a S-3 ligand field, i.e., the immediate one-electron reduction products of the oxyl-oxo (S-total = 6) and hydroxo-oxo (S-total = 3) species in the S-3 state. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Usefulness of intestinal ultrasound to detect small intestinal stenosis in patients with Crohn's disease EN Keiko TAKEUCHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Standardized incidence ratios of malignant neoplasms among patients with pneumoconiosis EN Tatsuya MICHIBATA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Blocking EP4 downregulates tumor metabolism and synergizes with anti-PD-1 therapy to activate natural killer cells in a lung adenocarcinoma model EN Miho TOKUMASU Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0959-3993 38 12 2022 Second extracellular protease mediating maturation of Vibrio mimicus hemolysin 241 EN Shin-ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Norie Toko Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tetsuya Dodo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ayako Nanko Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tamaki Mizuno Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Vibrio mimicus is a bacterium that causes gastroenteritis in humans. This pathogen produces an enterotoxic hemolysin called V. mimicus hemolysin (VMH), which is secreted extracellularly as an inactive 80-kDa protoxin and converted to a 66-kDa mature toxin through cleavage between Arg(151) and Ser(152). The 56-kDa serine protease termed V. mimicus trypsin-like protease (VmtA) is known to mediate this maturating process. However, some strains including strain ES-20 does not possess the vmtA gene. In the present study, the vmtA-negative strains were found to have a replaced gene that encodes a 43-kDa (403 aa) precursor of a serine protease designated by VmtX (V. mimicus trypsin-like protease X). To examine whether VmtX is also involved in the maturation of VMH, VmtX was isolated from the culture supernatant of V. mimicus strain NRE-20, a metalloprotease-negative mutant constructed from strain ES-20. Concretely, the culture supernatant was fractionated with 70% saturated ammonium sulfate and subjected to affinity column chromatography using a HiTrap Benzamidine FF column. The analysis of the N-terminal amino acid sequences of the proteins in the obtained VmtX preparation indicated that the 39-kDa protein was active VmtX consisting of 371 aa (Ile(33)-Ser(403)). The VmtX preparation was found to activate pro-VMH through generation of the 66-kDa protein. Additionally, treatment of the VmtX preparation with serine protease inhibitors, such as leupeptin and phenylmethylsulfonyl fluoride, significantly suppressed the activities to hydrolyze the specific peptide substrate and to synthesize the 66-kDa toxin. These findings indicate that VmtX is the second protease that mediats the maturation of VMH. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1068-9265 30 2 2022 Effect of Patient-Participation Continuous Nutritional Counseling in Gastric Cancer Patients who Underwent Gastrectomy 1110 1118 EN Nobuo Takata 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 Shinji Kuroda Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunsuke Tanabe Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Naoaki Maeda Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kazuhiro Noma Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ayako Takahashi Department of Clinical Nutrition, Okayama University Hospital Yuzo Umeda Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kenichi Shikata Department of Clinical Nutrition, Okayama University Hospital, Okayama, Japan Center for Innovative Clinical Medicine, Okayama University Hospital Kazuhide Ozaki Department of Gastroenterological Surgery, Kochi Health Sciences Center Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Background. Body weight loss (BWL) and skeletal muscle loss (SML) are inevitable after gastrectomy for gastric cancer (GC) and can decrease patients’ quality of life (QOL) and survival.<br> Objective. The aim of this retrospective study was to evaluate the effect of perioperative and post-discharge patient participation in continuous nutritional counseling (CNC) on post-gastrectomy BWL and SML.<br> Methods. Ninety-three patients with GC who underwent curative gastrectomy between March 2018 and July 2019 were analyzed. Patients received either pre-discharge nutritional counseling alone (control group, n = 49) or patient-participation CNC (CNC group, n = 44) after gastrectomy. Differences between percentage BWL (%BWL), percentage SML (%SML), and nutrition-related blood parameters between the preoperative values and those at 12 months after surgery were compared between the groups.<br> Results. Compared with the control group, %BWL was significantly lower in the CNC group at 1 month (−6.2 ± 2.5% vs. −7.9 ± 3.3%, p = 0.005), 6 months (−7.8 ± 6.6% vs. −12.3 ± 6.4%, p = 0.001) and 12 months (−7.9 ± 7.6% vs. −13.2 ± 8.2%, p = 0.002), and %SML was significantly lower in the CNC group at 12 months (−5.3 ± 10.3% vs. −12.8 ± 12%, p = 0.002). Regarding nutrition-related blood parameters, change in total cholesterol was significantly lower in the CNC group than the control group at 12 months after surgery (p = 0.02). Multivariate analysis identified no CNC as an independent risk factor for severe BWL (p = 0.001) and SML (p = 0.006) at 12 months after surgery.<br> Conclusions. Following gastrectomy, patient-participation CNC prevented postoperative BWL and SML after surgery. These results support the induction of such a CNC program in these patients. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0270-7314 43 2 2022 Commodity momentum decomposition 198 216 EN Yasuhiro Iwanaga The Faculty of Economic Sciences, Hiroshima Shudo University Ryuta Sakemoto Faculty of Humanities and Social Sciences, Okayama University This study decomposes the momentum factor (MOM) in the commodity futures market. A high-to-price (HTP) factor generates a higher Sharpe ratio than a price-to-high (PTH) factor. We uncover that the profitability mechanisms across three momentum factors are different. The positive returns on MOM and PTH are associated with overconfidence and strong self-attribution. In contrast, HTP is linked to investors’ underreaction and the information diffusion process. Moreover, we find that positive demand shocks raise the return on HTP. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1868-6974 29 12 2022 Efficacy of intraductal placement of non‐flared fully‐covered metal stent for refractory perihilar benign biliary strictures: A multicenter prospective study with long‐term observation 1300 1307 EN Kazuyuki Matsumoto Department of Gastroenterology and Hepatology Okayama University Hospital Hironari Kato Department of Gastroenterology and Hepatology Okayama University Hospital Masakuni Fujii Department of Internal Medicine Okayama Saiseikai General Hospital Toru Ueki Departments of Internal Medicine, Fukuyama City Hospital Yosuke Saragai Department of Gastroenterology, Iwakuni Medical Center Hirofumi Tsugeno Department of Gastroenterology, Tsuyama Central Hospital Tomohiko Mannami Department of Gastroenterology, National Hospital Organization Okayama Medical Center Hiroyuki Okada Department of Gastroenterology and Hepatology Okayama University Hospital Background: Endoscopic fully-covered self-expandable metal stents (FCSEMSs) are used to treat benign biliary strictures (BBSs); however, treatment for perihilar BBSs is technically challenging. The aim of this study was to evaluate the usefulness of an unflared FCSEMS designed for intraductal placement in patients with refractory perihilar BBS. <br> Methods: Twenty-two consecutive patients with perihilar BBS unresolved by endoscopic plastic stent placement at 13 tertiary medical centers were prospectively enrolled. The FCSEMS was placed above the papilla and removed after 4 months. The primary outcome was stricture resolution at 4 months, and the secondary outcomes were technical success, stent removal, adverse events, and recurrence. <br> Results: The technical success rate of intraductal FCSEMS placement was 100%, and plastic stent placement at contralateral or side branch was performed in 86% of patients. The rate of successful stent removal at 4 months was 100%, and stricture resolution was observed in 91% of patients. Stent migration or stent-induced de novo stricture did not occur in any patient. The stricture recurrence rate was 16%, and the median (interquartile range) follow-up duration was 2.8 (1.6-3.3) years. <br> Conclusions: Intraductal placement of unflared FCSEMS is effective treatment for refractory perihilar BBS. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1865-7257 15 6 2022 A case of endoscopic retrograde cholangiopancreatography-related main pancreatic duct perforation salvaged by endoscopic ultrasonography-guided pancreatic duct drainage 1179 1184 EN Ryosuke Sato Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Kosaku Morimoto Department of Gastroenterology and Hepatology, Okayama University Hospital Hiroyuki Terasawa Department of Gastroenterology and Hepatology, Okayama University Hospital Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Hospital Tatsuhiro Yamazaki Department of Gastroenterology and Hepatology, Okayama University Hospital Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Hospital We herein report a 78-year-old man who underwent endoscopic retrograde cholangiopancreatography (ERCP) to examine main pancreatic duct (MPD) stenosis. During ERCP, MPD perforation occurred due to the cytology brush maneuver. Endoscopic pancreatic stenting to bridge the perforated site failed because the MPD was bent and formed a loop. Thus, we placed the stent at the proximal perforated side. The patient developed retroperitoneal perforation and pancreatic fistula with infection, showing a worsening condition. Pancreatic duct drainage was not effective, so we performed endoscopic ultrasonography-guided pancreatic duct drainage. Subsequently, he gradually improved and was discharged 3 months after initial ERCP. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0140-7791 45 11 2022 FE UPTAKE‐INDUCING PEPTIDE1 maintains Fe translocation by controlling Fe deficiency response genes in the vascular tissue of Arabidopsis 3322 3337 EN Satoshi Okada Group of Environmental Stress Response Systems, Institute of Plant Science and Resources, Okayama University Gui J. Lei Group of Plant Stress Physiology, Institute of Plant Science and Resources, Okayama University Naoki Yamaji Group of Plant Stress Physiology, Institute of Plant Science and Resources, Okayama University Sheng Huang Group of Plant Stress Physiology, Institute of Plant Science and Resources, Okayama University Jian F. Ma Group of Plant Stress Physiology, Institute of Plant Science and Resources, Okayama University Keiichi Mochida Crop Design Research Team, Institute of Plant Science and Resources, Okayama University Takashi Hirayama Group of Environmental Stress Response Systems, Institute of Plant Science and Resources, Okayama University FE UPTAKE-INDUCING PEPTIDE1 (FEP1), also named IRON MAN3 (IMA3) is a short peptide involved in the iron deficiency response in Arabidopsis thaliana. Recent studies uncovered its molecular function, but its physiological function in the systemic Fe response is not fully understood. To explore the physiological function of FEP1 in iron homoeostasis, we performed a transcriptome analysis using the FEP1 loss-of-function mutant fep1-1 and a transgenic line with oestrogen-inducible expression of FEP1. We determined that FEP1 specifically regulates several iron deficiency-responsive genes, indicating that FEP1 participates in iron translocation rather than iron uptake in roots. The iron concentration in xylem sap under iron-deficient conditions was lower in the fep1-1 mutant and higher in FEP1-induced transgenic plants compared with the wild type (WT). Perls staining revealed a greater accumulation of iron in the cortex of fep1-1 roots than in the WT root cortex, although total iron levels in roots were comparable in the two genotypes. Moreover, the fep1-1 mutation partially suppressed the iron overaccumulation phenotype in the leaves of the oligopeptide transporter3-2 (opt3-2) mutant. These data suggest that FEP1 plays a pivotal role in iron movement and in maintaining the iron quota in vascular tissues in Arabidopsis. No potential conflict of interest relevant to this article was reported.

Oxford University Press Acta Medica Okayama 0266-8254 75 6 2022 Characterization of the oral and fecal microbiota associated with atopic dermatitis in dogs selected from a purebred Shiba Inu colony 1607 1616 EN Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Takafumi Osumi Laboratory of Veterinary Internal Medicine, Division of Animal Life Science, Graduate School, Tokyo University of Agriculture and Technology Keijiro Mizukami School of Veterinary Medicine, Azabu University Tomoki Fukuyama School of Veterinary Medicine, Azabu University Ayaka Shima Anicom Specialty Medical Institute Inc. Asaka Unno School of Veterinary Medicine, Azabu University Iyo Takemura‐Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Yumi Une Faculty of Veterinary Medicine, Okayama University of Science Hironobu Murakami School of Veterinary Medicine, Azabu University Masahiro Sakaguchi School of Veterinary Medicine, Azabu University Atopic dermatitis (AD) is a chronic and relapsing multifactorial inflammatory skin disease that also affects dogs. The oral and gut microbiota are associated with many disorders, including allergy. Few studies have addressed the oral and gut microbiota in dogs, although the skin microbiota has been studied relatively well in these animals. Here, we studied the AD-associated oral and gut microbiota in 16 healthy and nine AD dogs from a purebred Shiba Inu colony. We found that the diversity of the oral microbiota was significantly different among the dogs, whereas no significant difference was observed in the gut microbiota. Moreover, a differential abundance analysis detected the Family_XIII_AD3011_group (Anaerovoracaceae) in the gut microbiota of AD dogs; however, no bacterial taxa were detected in the oral microbiota. Third, the comparison of the microbial co-occurrence patterns between AD and healthy dogs identified differential networks in which the bacteria in the oral microbiota that were most strongly associated with AD were related with human periodontitis, whereas those in the gut microbiota were related with dysbiosis and gut inflammation. These results suggest that AD can alter the oral and gut microbiota in dogs. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0163-3864 85 8 2022 First Total Synthesis of Reassigned Echinosulfonic Acid D 2122 2125 EN Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ren Nakajima Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiki Yamashiro Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Sawada Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Echinosulfonic acid D, a sponge metabolite whose structure was recently reassigned, was synthesized for the first time. The key step is the double indolization of dimethylbarbituric acid using the umpolung indole reagent, followed by a hydrolysis/decarboxylation/esterification sequence. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 10 5 2022 Japanese case of Charcot–Marie–Tooth disease type 2Z with severe retinitis pigmentosa 266 268 EN Emi Nomura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koh Tadokoro Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryo Sasaki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumi Nakata Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumiko Nakano Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiro Ando Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University Hiroshi Takashima Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Charcot-Marie-Tooth disease type 2Z (CMT2Z) shows highly variable clinical features. We report the first Japanese CMT2Z patient with a c.754C>T (p.R252W) substitution of the MORC2 gene, complicating severe retinitis pigmentosa. The MORC2 mutants were involved in a decrease in cell survival through induction of apoptosis. Thus, the MORC2 mutation might be involved in the degeneration of photoreceptors and the development of retinitis pigmentosa. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 11 16 2022 Association between Immediate Postoperative Radiographic Findings and Failed Internal Fixation for Trochanteric Fractures: Systematic Review and Meta-Analysis 4879 EN Norio Yamamoto Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasushi Tsujimoto Scientific Research Works Peer Support Group (SRWS-PSG) Suguru Yokoo Department of Orthopedic Surgery, National Hospital Organization Okayama Medical Center Koji Demiya Department of Orthopedic Surgery, Tsuyama Chuo Hospital Madoka Inoue Scientific Research Works Peer Support Group (SRWS-PSG) Tomoyuki Noda Department of Orthopedic Surgery and Traumatology, Kawasaki Medical School General Medical Center Toshifumi Ozaki Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Failed internal fixations for trochanteric fractures have a strong negative impact owing to increased postoperative mortality and high medical costs. However, evidence on the prognostic value of postoperative radiographic findings for failed internal fixations is limited. We aimed to clarify the association between comprehensive immediate postoperative radiographic findings and failed internal fixation using relative and absolute risk measures. We followed the meta-analysis of observational studies in epidemiology guidelines and the Cochrane handbook. We searched specific databases in November 2021. The outcomes of interest were failed internal fixation and cut-out. We pooled the odds ratios and 95% confidence intervals using a random-effects model and calculated the number needed to harm for each outcome. Thirty-six studies involving 8938 patients were included. The certainty of evidence in the association between postoperative radiographic findings and failed internal fixation or cut-out was mainly low or very low except for the association between intramedullary malreduction on the anteromedial cortex and failed internal fixation. Moderate certainty of evidence supported that intramedullary malreduction on the anteromedial cortex was associated with failed internal fixation. Most postoperative radiographic findings on immediate postoperative radiographs for trochanteric fractures were uncertain as prognostic factors for failed internal fixations. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0014-5793 596 23 2022 Loss of function of an Arabidopsis homologue of JMJD6 suppresses the dwarf phenotype of acl5, a mutant defective in thermospermine biosynthesis 3005 3014 EN Hirotoshi Matsuo Graduate School of Natural Science and Technology, Okayama University Hiroko Fukushima Graduate School of Natural Science and Technology, Okayama University Shinpei Kurokawa Graduate School of Natural Science and Technology, Okayama University Eri Kawano Graduate School of Natural Science and Technology, Okayama University Takashi Okamoto Graduate School of Natural Science and Technology, Okayama University Hiroyasu Motose Graduate School of Natural Science and Technology, Okayama University Taku Takahashi Graduate School of Natural Science and Technology, Okayama University In Arabidopsis thaliana, the ACL5 gene encodes thermospermine synthase and its mutant, acl5, exhibits a dwarf phenotype with excessive xylem formation. Studies of suppressor mutants of acl5 reveal the involvement of thermospermine in enhancing mRNA translation of the SAC51 gene family. We show here that a mutant, sac59, which partially suppresses the acl5 phenotype, has a point mutation in JMJ22 encoding a D6-class Jumonji C protein (JMJD6). A T-DNA insertion allele, jmj22-2, also partially suppressed the acl5 phenotype while mutants of its closest two homologs JMJ21 and JMJ20 had no such effects, suggesting a unique role for JMJ22 in plant development. We found that mRNAs of the SAC51 family are more stabilized in acl5 jmj22-2 than in acl5. No potential conflict of interest relevant to this article was reported.

BMJ Publishing Group Acta Medica Okayama 2044-6055 12 7 2022 Efficacy of soft palatal augmentation prosthesis for oral functional rehabilitation in patients with dysarthria and dysphagia: a protocol for a randomised controlled trial e060040 EN Tomonori Yokoyama Department of Occlusal & Oral Functional Rehabilitation, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Takao Mukai Division of Oral Surgery, Kawasaki Medical School Hospital Naoki Kodama Department of Occlusal & Oral Functional Rehabilitation, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Kana Takao Division of Oral Surgery, Kawasaki Medical School Hospital Takashi Hiraoka Department of Rehabilitation Medicine, Kawasaki Medical School Nobuyuki Arai Department of Rehabilitation Medicine, Kawasaki Medical School Jitsuro Yano Department of Speech-Language Pathology and Audiology, Faculty of Rehabilitation, Kawasaki University of Medical Welfare Hiroaki Nagatsuka Department of Occlusal & Oral Functional Rehabilitation, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Yousuke Manda Department of Occlusal & Oral Functional Rehabilitation, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Kozo Hanayama Department of Rehabilitation Medicine, Kawasaki Medical School Shogo Minagi Department of Occlusal & Oral Functional Rehabilitation, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Introduction Palatal augmentation prosthesis (PAP) is used in patients with articulation and swallowing disorders caused by postoperative loss of tongue tissue due to tongue cancer, cerebrovascular disease sequelae and age-related hypofunction. We have previously reported a newly designed soft PAP fabricated using an thermoplastic material that is particularly appropriate for early intervention. However, the effect of soft PAP on oral function improvement remains to be elucidated. The aim of this study is to investigate whether soft PAP can improve dysarthria and dysphagia occurring as cerebrovascular disease sequelae. Methods and analysis This prospective, randomised, controlled trial will compare the immediate and training effects of rehabilitation using soft PAP with those of rehabilitation without using it. Primary outcomes are the single-word intelligibility test score and pharyngeal transit time (PTT). Secondary outcomes are tongue function (evaluated based on maximum tongue pressure, repetitions of tongue pressure and endurance of tongue pressure), articulation function (evaluated based on speech intelligibility, oral diadochokinesis, Voice-Related Quality of Life (V-RQOL)) and swallowing function (evaluated using Eating Assessment Tool-10). The study results will help determine the efficacy of Soft PAP in improving functional outcomes of word intelligibility and PTT. We hypothesised that early rehabilitation using Soft PAP would more effectively improve articulation and swallowing function compared with conventional rehabilitation without using soft PAP. Ethics and dissemination Ethical approval was obtained from the Okayama University Certified Review Board. The study findings will be published in an open access, peer-reviewed journal and presented at relevant conferences and research meetings. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0887-0624 36 18 2022 Structure Selectivity of Mixed Gas Hydrates and Group 14 Clathrates 10667 10674 EN Masakazu Matsumoto Research Institute for Interdisciplinary Science, Okayama University Hideki Tanaka Toyota Physical and Chemical Research Institute The structure selectivity of mixed gas hydrates and group 14 clathrates is examined on the basis of statistical mechanical theories and the empirical rule on the topological constraint of the Frank-Kasper phases. The most stable structure is revealed by the generalized phase diagram, where the chemical potential differences in the three canonical forms of clathrates are independent variables. The most stable structure incorporating individual guest species is evaluated by the locus of the chemical potential differences on this generalized phase diagram. We show that the method developed here is simple but powerful to estimate roughly phase behaviors of clathrate compounds in a wide range of thermodynamic conditions, which is demonstrated by two applications: the generalized phase diagram of group 14 element clathrates and the phase behavior of mixed gas hydrates. The present theory leads to proposals of phase change agents, of which the addition sensitively influences the structure selectivity, encompassing even minor structures. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0924-090X 110 1 2022 Quasi-periodic motions in a two-class economy with technology choice: an extreme case 945 961 EN Takao Asano Faculty of Economics, Okayama University Akihisa Shibata Institute of Economic Research, Kyoto University Masanori Yokoo Faculty of Economics, Okayama University This paper constructs a simple overlapping generations (OLG) model with the working and capitalist classes and two types of production technologies. The behavior of agents belonging to the working class is basically the same as that in the standard Diamond (Am Econ Rev 55:1126-1150, 1965) type OLG model, whereas agents belonging to the capitalist class face two available technologies, select the one with a higher return on capital, and bequeath their assets to the next generation without supplying labor. Using techniques concerning the circle map in dynamical systems theory, we show that in an extreme case in which one technology is linear and the other is of the Leontief type, the economy exhibits bounded, non-periodic but non-chaotic motions for a large set of parameter values. We provide explicit formulas for the rotation number and the absolutely continuous invariant probability measure of the model. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-1068 33 5 2022 Larger sagittal inter-screw distance/tibial width ratio reduces delayed union or non-union after arthroscopic ankle arthrodesis 1557 1563 EN Suguru Yokoo Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenta Saiga Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Demiya Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hideki Ohashi Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiro Horita Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background<br> Arthroscopic ankle arthrodesis (AAA) has risks of complications, such as delayed union and non-union. The number and direction of the inserted screws have been reported as important factors affecting the time to union of AAA. However, the ratio of inter-screw distance (ISD) to tibial width (TW) in different planes has not been investigated. Therefore, we aimed to explore the effect of this ratio on bone union following AAA.<br> <br> Methods<br> We retrospectively enrolled 63 patients (64 ankles) undergoing AAA from 2013 to 2019. Then, their age, body mass index (BMI), sex, diabetes mellitus (DM) status, Takakura–Tanaka classification, number of screws and radiographic parameters were analysed.<br> <br> Results<br> The patients had a mean age of 70.3 (range, 45–91) years. Bone fusion was achieved in 57 ankles (89%) in a mean period of 3.3 (range, 2–6) postoperative months. There were four cases of delayed union and three of non-union. No significant differences in age, BMI, sex, DM, Takakura–Tanaka classification, and number of screws could be detected between the groups. However, the sagittal ISD/TW ratio was significantly larger in the union group than in the delayed/non-union group with a cut-off value of 57.0%.<br> <br> Conclusion<br> Larger sagittal ISD/TW ratios result in reduced post-AAA delayed union or non-union. The surgeon should be aware that the anterior and posterior screw widths should be approximately 60% or more of the anteroposterior width of the tibia. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1320-5358 27 9 2022 Simulation for ultrasound‐guided renal biopsy using boiled egg 753 757 EN Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama Japan Shinji Kitamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama Japan Haruhito A. Uchida Department of Chronic Kidney Disease and Cardiovascular Disease Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama Japan Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama Japan Real-time ultrasound-guided renal biopsy is generally applied to diagnose multiple kidney diseases. A practical simulation model is desired since it is an invasive technique with higher risks of complications such as bleeding. We developed a simple simulation tool for ultrasound-guided renal biopsy using boiled eggs. Boiled chicken eggs were embedded in the agar, and a biopsy simulation was performed using a real-time ultrasound-guided technique as the renal biopsy simulator by trainees and biopsyproficient nephrologists, and the feedback from the participants was obtained. The ultrasonographic evaluation revealed a clear contrast between egg yolk and white, which clearly mimicked the kidney cortex and medulla region. In addition, we observed the needle entering the egg white under needle penetration, and we obtained the biopsy core consisting of egg white. As for the simulations, all the participants succeeded in obtaining the appropriate samples. A total of 92% of the trainees agreed that the simulation could reduce their fears of performing renal biopsies in patients. In addition, all the trainees and biopsy-proficient nephrologists recommend using the simulator for trainees before conducting renal biopsies on patients. The total cost of the simulator was low (< USD 1/simulator). Collectively, our simulation tool using boiled eggs may be a good candidate for practical simulation models of renal biopsy. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 10 5 2022 A Japanese case of successful surgical resection of cerebral cavernous malformations with a CCM2 mutation 255 258 EN Emi Nomura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshio Omote Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumiko Nakano Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsuya Sasaki Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Akagawa Tokyo Women's Medical University Institute for Integrated Medical Sciences Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Cerebral cavernous malformations (CCMs) are congenital abnormalities of cerebral vessels. Surgical resection is rarely considered for the control of epilepsy in a first seizure patient with vascular malformation. In contrast, lesions that produce repetitive or progressive symptoms should be considered for surgical resection as treatment. Herein, we report a Japanese patient with a CCM2 mutation, c.609G>A (p.K203K) substitution, who showed drug-resistant epilepsy and dramatic improvement after surgical resection. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1444-1586 22 8 2022 Trends in places and causes of death among centenarians in Japan from 2006 to 2016 675 680 EN Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsukasa Higashionna Department of Pharmacy, Okayama University Hospital Akinori Maruo Department of Pharmacy, Okayama University Hospital Soichiro Ushio Department of Pharmacy, Okayama University Hospital Yoshito Zamami Department of Pharmacy, Okayama University Hospital Ko Harada Department of Medicine, Icahn School of Medicine at Mount Sinai Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aim<br> Amid the global aging, an establishment of healthcare policies for the aged population is a common issue to be addressed. However, few studies on centenarians have reported place and cause of death (PoD and CoD, respectively) as indicators of end-of-life care quality. This study aimed to analyze trends in PoD and CoD among centenarians in Japan.<br> <br> Methods<br> Data from death certificates from Japanese vital statistics were analyzed; 205 513 deaths occurred among centenarians (aged ≥100 years) in Japan during the period from 2006 to 2016. PoD prevalence was calculated for each CoD. Trends in PoD prevalence were analyzed using the Joinpoint regression model. Changing points, annual percentage changes, and average annual percentage changes (AAPCs) were calculated to examine trends.<br> <br> Results<br> The number of deaths more than doubled from 10 340 in 2006 to 26 427 in 2016. PoDs were composed of hospitals (52.7%), nursing homes (31.4%), own homes (13.6%) and others (2.2%). Dementia and old age increased rapidly as CoD. Proportions of hospital and home deaths decreased, with AAPCs of −2.3% (95% confidence interval [CI], −2.6 to −1.9) and −2.3% (95% CI, −3.2 to −1.4), respectively. Conversely, the proportion of deaths in nursing homes rapidly increased, with an AAPC of 6.8% (95% CI, 6.0–7.7).<br> <br> Conclusions<br> The results revealed changes in PoD among centenarians in Japan. Understanding these transitions is indispensable for health policy in aging societies. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1042-7147 33 8 2022 Preparation of cellulose nanocrystals coated with polymer crystals and their application in composite films 2511 2518 EN Tetsuya Uchida Graduate School of Natural Science and Technology, Okayama University Ryohei Nishioka Graduate School of Natural Science and Technology, Okayama University Risa Yanai Graduate School of Natural Science and Technology, Okayama University Increasing the dispersibility of cellulose nanocrystals (CNCs) as a reinforcing material is highly desirable to obtain composites with enhanced mechanical properties. To this aim, nanocomposite fibers (NCF(CNC/polymer)) were fabricated by coating CNCs with polymer crystals. Poly(vinyl alcohol) (PVA) and poly(vinyl alcohol-co-ethylene) (EVOH) were crystallized from a dilute solution in the presence of CNCs, which acted as nucleating agents for polymer crystal growth on the CNC surface. NCF consisting of CNCs coated with PVA crystals (NCF(CNC/PVA)) and CNCs coated with EVOH crystals (NCF(CNC/EVOH)) were successfully obtained. Both NCF(CNC/polymer) showed good dispersibility in water, even after drying, and were used to prepare composite films with improved mechanical properties. The reinforcement effect of NCF(CNC/PVA) was greater than that of pure CNCs and NCF(CNC/EVOH). The PVA composite films exhibited optical transmittance above 99% compared with additive-free PVA films. No agglomerates appeared even under the optical microscopic observation of the PVA composite film, and NCF(CNC/PVA) dispersibility was extremely good. NCF(CNC/PVA)-added PVA composite films exhibited increased glass transition temperature compared with additive-free PVA films, and the crystallinity of the PVA film increased. The highly dispersed CNCs in the PVA matrix and the increase in the glass transition temperature and crystallinity caused an increase in the mechanical modulus of the PVA composite film at low NCF(CNC/PVA) content. Furthermore, the effect of the morphologies of cellulose nanofibers and CNCs on the mechanical properties of the composite films prepared using the respective NCFs was investigated. No potential conflict of interest relevant to this article was reported.

Oxford University Press Acta Medica Okayama 1460-2377 34 11 2022 A variety of ‘exhausted’ T cells in the tumor microenvironment 563 570 EN Joji Nagasaki Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yosuke Togashi Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University In T-cell biology, ‘exhaustion’ was initially described as a hyporesponsive state in CD8+ T cells during chronic infections. Recently, exhaustion has been recognized as a T-cell dysfunctional state in the tumor microenvironment (TME). The term ‘exhaustion’ is used mainly to refer to effector T cells with a reduced capacity to secrete cytokines and an increased expression of inhibitory receptors. The up-regulation of exhaustion-related inhibitory receptors, including programmed cell death protein 1 (PD-1), in such T cells has been associated with the development of tumors, prompting the development of immune checkpoint inhibitors. In addition to CD8+ T cells, CD4+ T cells, including the regulatory T (Treg) cell subset, perform a wide variety of functions within the adaptive immune system. Up-regulation of the same inhibitory receptors that are associated with CD8+ T-cell exhaustion has also been identified in CD4+ T cells in chronic infections and cancers, suggesting a similar CD4+ T-cell exhaustion phenotype. For instance, high expression of PD-1 has been observed in Treg cells in the TME, and such Treg cells can play an important role in the resistance to PD-1 blockade therapies. Furthermore, recent progress in single-cell RNA sequencing has shown that CD4+ T cells with cytotoxic activity are also vulnerable to exhaustion. In this review, we will discuss novel insights into various exhausted T-cell subsets, which could reveal novel therapeutic targets and strategies to induce a robust anti-tumor immune response. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-1068 33 4 2022 Medial meniscus posterior root repair influences sagittal length and coronal inclination of the anterior cruciate ligament: a retrospective study 1255 1262 EN Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Hospital Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Hospital Yuya Kodama Department of Orthopaedic Surgery, Okayama University Hospital Takaaki Hiranaka Department of Orthopaedic Surgery, Okayama University Hospital Keisuke Kintaka Department of Orthopaedic Surgery, Okayama University Hospital Yusuke Kamatsuki Department of Orthopaedic Surgery, Okayama University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Hospital Purpose　Medial meniscus (MM) posterior root tears (PRTs) lead to abnormal kinematic changes in the knee and may induce pathological external rotation of the tibia during knee flexion. This study aimed to investigate changes in the length and inclination of the anterior cruciate ligament (ACL) after MM posterior root repair using magnetic resonance imaging (MRI). <br> Methods　This retrospective study included 44 patients who underwent MM posterior root repair between 2016 and 2019. Clinical outcomes were evaluated before and after surgery. MRI examinations were performed at 10 degrees/90 degrees of knee flexion preoperatively and 3 months postoperatively. The ACL length, proximal angle, and distal angle were determined using the sagittal view. MM extrusion and ACL inclination angle were determined using the coronal view. <br> Results　Clinical outcomes significantly improved 1 year after surgery. The postoperative ACL length (29.7 +/- 2.4 mm) and proximal angle (47.0 +/- 7.4 degrees) at 90 degrees of knee flexion decreased relative to the preoperative values (31.5 +/- 2.3 mm and 51.8 +/- 8.7 degrees, P < 0.01). The postoperative ACL inclination (64.9 +/- 5.6 degrees) at 10 degrees of knee flexion decreased relative to the preoperative value (69.7 +/- 5.6 degrees, P < 0.01). <br> Conclusion　Pathologically-stretched linear ACL at 90 degrees of knee flexion and a steep ACL inclination at 10 degrees of knee flexion could be reduced after MM posterior root repair. This suggests that pullout repair could restore MM function as a secondary stabilizer, thereby preventing meniscal and cartilage degeneration. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 1932-7447 126 22 2022 Role of Oxygen Vacancy in the Photocarrier Dynamics of WO3 Photocatalysts: The Case of Recombination Centers 9257 9263 EN Kosaku Kato Graduate School of Natural Science and Technology, Okayama University Yohei Uemura Institute for Molecular Science Kiyotaka Asakura Institute for Catalysis, Hokkaido University Akira Yamakata Graduate School of Natural Science and Technology, Okayama University Defects in powder photocatalysts determine the photocatalytic activity. The addition of defects sometimes enhances the activity, but sometimes decreases it. However, the factors determining the difference between these cases have not been fully elucidated yet. Herein, we investigated the effects of oxygen vacancies on photocarrier dynamics in WO3 powder using broadband transient absorption spectroscopy. It was found that the decay of deeply trapped electrons was accelerated when the number of oxygen vacancies was increased by H-2 reduction. This result suggests that oxygen vacancies in WO3 mainly act as recombination centers. This is in contrast to many other photocatalysts such as TiO2 and SrTiO3, where the carrier lifetime increases with increasing oxygen vacancy concentration. These differences can be attributed to the difference in the distance between oxygen vacancies. When defects are dispersed, trapped electrons need to travel over long distances by repeatedly hopping and tunneling between defects to combine with holes, resulting in decelerated recombination. In contrast, when the defects are connected or located close together, the trapped electrons can readily migrate among defects, leading to enhanced recombination. Control of the distance between defects is thus important for enhancing photocatalytic activity. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0947-6539 28 37 2022 Design and Synthesis of Glycosylated Cholera Toxin B Subunit as a Tracer of Glycoprotein Trafficking in Organelles of Living Cells e202201253 EN Yuta Maki Department of Chemistry, Graduate School of Science, Osaka University Kazuki Kawata Department of Chemistry, Graduate School of Science, Osaka University Yanbo Liu Department of Chemistry, Graduate School of Science, Osaka University Kang‐Ying Goo Department of Chemistry, Graduate School of Science, Osaka University Ryo Okamoto Department of Chemistry, Graduate School of Science, Osaka University Yasuhiro Kajihara Department of Chemistry, Graduate School of Science, Osaka University Ayano Satoh Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Glycosylation of proteins is known to be essential for changing biological activity and stability of glycoproteins on the cell surfaces and in body fluids. Delivering of homogeneous glycoproteins into the endoplasmic reticulum (ER) and the Golgi apparatus would enable us to investigate the function of asparagine-linked (N-) glycans in the organelles. In this work, we designed and synthesized an intentionally glycosylated cholera toxin B-subunit (CTB) to be transported to the organelles of mammalian cells. The heptasaccharide, the intermediate structure of various complex-type N-glycans, was introduced to the CTB. The synthesized monomeric glycosyl-CTB successfully entered mammalian cells and was transported to the Golgi and the ER, suggesting the potential use of synthetic CTB to deliver and investigate the functions of homogeneous N-glycans in specific organelles of living cells. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0910-6340 38 4 2022 N-Benzoyl leucomethylene blue as a novel substrate for the assays of horseradish peroxidase by spectrophotometry and capillary electrophoresis–laser-induced fluorometry 651 655 EN Jianchao Ren Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takashi Kaneta Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Horseradish peroxidase (HRP) is an enzyme that is frequently employed in various assays because HRP catalyzes the oxidation reactions of chromogenic and fluorogenic compounds to produce chromophores and fluorophores, respectively. The results of this study show that N-benzoyl leucomethylene blue (BLMB) is an excellent substrate for enzyme assay using HRP. In the presence of hydrogen peroxide (H2O2), HRP catalyzed an oxidation reaction of BLMB that produced methylene blue with a deep blue color. Thus, absorption spectrophotometry and capillary electrophoresis-laser-induced fluorometry (CE-LIF) could be used to easily determine the produced methylene blue. Under the optimum conditions, absorption spectrophotometry showed a linear calibration curve that ranged from 25 to 500 mu g mL(-1). The reaction conditions were also applicable to CE-LIF, showing a linear range of from 25 to 500 mu g mL(-1) with limits of detection and quantification at 2 and 6 mu g mL(-1), respectively. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 3 2022 The Impact of Medical Students Teaching Basic Life Support to Laypersons 265 271 EN Yoshinori Kosaki 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 Atsuyoshi Iida Department of Emergency Medicine, Japanese Red Cross Okayama Hospital Hiromi Ihoriya Department of General Medicine, Okayama University Hospital Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Taihei Yamada Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hirotsugu Yamamoto Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shunsuke Nakamura Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuhiro Mandai Department of Emergency Medicine, The JIKEI University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Original Article 10.18926/AMO/63720 Basic life support (BLS) courses for laypersons, including cardiopulmonary resuscitation (CPR) training, is known to improve outcomes of out-of-hospital cardiac events. We asked medical students to provide BLS training for laypersons as a part of their emergency medicine education and evaluated the effects of training on the BLS skills of laypersons. We also used a questionnaire to determine whether the medical students who provided the BLS training were themselves more confident and motivated to perform BLS compared to students who did not provide BLS training. The proportions of laypersons who reported confidence in checking for a response, performing chest compressions, and automated external defibrillator (AED) use were significantly increased after the BLS training. The proportions of medical students who reported increased confidence/motivation in terms of understanding BLS, checking for a response, chest compression, use of AED, and willingness to perform BLS were significantly greater among medical students who provided BLS instructions compared to those who did not. BLS instruction by medical students was associated with an improvement in laypersons’ CPR accuracy and confidence in responding to cardiac arrest. The results indicate that medical students could gain understanding, confidence, and motivation in regard to their BLS skills by teaching BLS to laypersons. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2379-3694 7 4 2022 Dip-and-Read, Organic Solvent-Compatible, Paper-Based Analytical Devices Equipped with Chromatographic Separation for Indole Analysis in Shrimp 1194 1200 EN Sasikarn Seetasang Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takashi Kaneta Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University We developed an organic solvent-compatible paper-based analytical device (PAD) for the quantitative analysis of indole, which is an indicator of shrimp freshness. Although indole is insoluble in water, ethyl acetate is a suitable solvent to dissolve and extract indole from shrimp. The PADs are fabricated using a cutting method that allows the use of an organic solvent because no hydrophobic barrier is needed to form fluidic channels. Ehrlich's reagent consists of 4-(dimethylamino)benzaldehyde and p-dimethylaminobenzaldehyde and was deposited onto the reaction zone of the PAD followed by lamination to prevent evaporation of the ethyl acetate. Samples are introduced into the PAD via immersion in organic sample solutions. When the PAD is immersed into an indole solution of ethyl acetate in a closed bottle, the sample solution penetrates the channel of the PAD and successively flows into the detection zone to form a hydrophilic colored product. The PADs provide a linear relationship between the logarithm of the indole concentration and the color intensity within a range of 1.0-20 ppm with correlation coefficients of r2 > 0.99. The limits of detection and quantification are 0.36 and 0.71 ppm, respectively. Relative standard deviations for both the intraday (n = 2) and interday (n = 3) precision were less than 2.5%. In the indole analysis of shrimp, the PADs separated the interfering orange-colored astaxanthin in the extract from the colored product of indole via the paper chromatographic principle. We used the PADs to investigate the degradation of shrimp, and the results showed a rapid increase in the indole level after 7 days. High-performance liquid chromatography verified the accuracy of the PADs by showing good agreement with the obtained indole levels. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Oral function, nutritional status and physical status in Japanese independent older adults EN Nanami Sawada Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Anti-high mobility group box 1 monoclonal antibody suppressed hyper-permeability and cytokine production in human pulmonary endothelial cells infected with influenza A virus EN Takahiro Nanba Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Association between intraoperative hyperlycemia and postoperative end-organ dysfunctions after cardiac surgery: A retrospetive observational study EN Shinsaku Matsumoto Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Analysis of clonality in cutaneous B-cell lymphoma and B-cell pseudolymphoma using skin flow cytometry: Comparison of immunophenotyping and gene rearrangement studies　 EN Yuki Nakagawa Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Luminal preloading with hydrogen-rich saline ameliorates ischemia-reperfusion injury following intestinal transplantation in rats EN Hirotsugu Yamamoto Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 PolyI:C suppresses TGF-β1-induced Akt phosphorylation and reduces the motility of A549 lung carcinoma cells EN Takahiro Yamaguchi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Japanese version of Patient-Rated Elbow Evaluation is a useful outcome measure that potentially reflects hand function in patients with rheumatoid arthritis who underwent total elbow arthroplasty EN Ryozo Harata Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Low-dose rituximab induction therapy is effective in immunological high-risk renal transplantation without increasing cytomegalovirus infection EN Kasumi Yoshinaga Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Inflammation of the adipose tissue in the retroperitoneal cavity adjacent to pelvic endometriosis EN Kotaro Kubo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0032-0781 63 5 2022 Sorghum Ionomics Reveals the Functional SbHMA3a Allele that Limits Excess Cadmium Accumulation in Grains 713 728 EN Fiona Wacera Wahinya Institute of Plant Science and Resources, Okayama University, Kiyoshi Yamazaki Graduate School of Agricultural and Life Sciences, The University of Tokyo Zihuan Jing Institute of Plant Science and Resources, Okayama University Tsuneaki Takami Institute of Plant Science and Resources, Okayama University Takehiro Kamiya Graduate School of Agricultural and Life Sciences, The University of Tokyo Hiromi Kajiya-Kanegae Research Center for Agricultural Information Technology, National Agriculture and Food Research Organization Hideki Takanashi Graduate School of Agricultural and Life Sciences, The University of Tokyo Hiroyoshi Iwata Graduate School of Agricultural and Life Sciences, The University of Tokyo Nobuhiro Tsutsumi Graduate School of Agricultural and Life Sciences, The University of Tokyo Toru Fujiwara Graduate School of Agricultural and Life Sciences, The University of Tokyo Wataru Sakamoto Institute of Plant Science and Resources, Okayama University Understanding uptake and redistribution of essential minerals or sequestering of toxic elements is important for optimized crop production. Although the mechanisms controlling mineral transport have been elucidated in rice and other species, little is understood in sorghum―an important C4 cereal crop. Here, we assessed the genetic factors that govern grain ionome profiles in sorghum using recombinant inbred lines (RILs) derived from a cross between BTx623 and NOG (Takakibi). Pairwise correlation and clustering analysis of 22 elements, measured in sorghum grains harvested under greenhouse conditions, indicated that the parental lines, as well as the RILs, show different ionomes. In particular, BTx623 accumulated significantly higher levels of cadmium (Cd) than NOG, because of differential root-to-shoot translocation factors between the two lines. Quantitative trait locus (QTL) analysis revealed a prominent QTL for grain Cd concentration on chromosome 2. Detailed analysis identified SbHMA3a, encoding a P1B-type ATPase heavy metal transporter, as responsible for low Cd accumulation in grains; the NOG allele encoded a functional HMA3 transporter (SbHMA3a-NOG) whose Cd-transporting activity was confirmed by heterologous expression in yeast. BTx623 possessed a truncated, loss-of-function SbHMA3a allele. The functionality of SbHMA3a in NOG was confirmed by Cd concentrations of F2 grains derived from the reciprocal cross, in which the NOG allele behaved in a dominant manner. We concluded that SbHMA3a-NOG is a Cd transporter that sequesters excess Cd in root tissues, as shown in other HMA3s. Our findings will facilitate the isolation of breeding cultivars with low Cd in grains or in exploiting high-Cd cultivars for phytoremediation. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0947-6539 28 37 2022 Indole Editing Enabled by HFIP‐Mediated Ring‐Switch Reactions of 3‐Amino‐2‐Hydroxyindolines e202201113 EN Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiki Yamashiro Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kaho Shimizu Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Sawada Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University We found the novel reactivity of hemiaminal as a precursor for indole editing at the multi-site. The HFIP-promoted indole editing of indoline hemiaminals affords 2-arylindoles through a ring-switch sequence. The key to success of this transformation is to use a cyclic hemiaminal as an a-amino aldehyde surrogate under transient tautomeric control. This transformation features mild reaction conditions and good yields with broad functional group tolerance. The utility of this transformation is presented through the one-pot protocol and the synthesis of isocryptolepine. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1742-464X 289 19 2022 Substrate recognition by Arg/Pro‐rich insert domain in calcium/calmodulin‐dependent protein kinase kinase for target protein kinases 5971 5984 EN Riku Kaneshige 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 Yuhei Harada Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Issei Kawamata Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Masaki Magari Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Naoki Kanayama 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 Hiroyuki Sakagami Department of Anatomy, Kitasato University School of Medicine Hiroshi Tokumitsu Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Calcium/calmodulin-dependent protein kinase kinases (CaMKKs) activate CaMKI, CaMKIV, protein kinase B/Akt, and AMP-activated protein kinase (AMPK) by phosphorylating Thr residues in activation loops to mediate various Ca2+-signaling pathways. Mammalian cells expressing CaMKK alpha and CaMKK beta lacking Arg/Pro-rich insert domain (RP-domain) sequences showed impaired phosphorylation of AMPK alpha, CaMKI alpha, and CaMKIV, whereas the autophosphorylation activities of CaMKK mutants remained intact and were similar to those of wild-type CaMKKs. Liver kinase B1 (LKB1, an AMPK kinase) complexed with STRAD and MO25 and was unable to phosphorylate CaMKI alpha and CaMKIV; however, mutant LKB1 with the RP-domain sequences of CaMKK alpha and CaMKK beta inserted between kinase subdomains II and III acquired CaMKI alpha and CaMKIV phosphorylating activity in vitro and in transfected cultured cells. Furthermore, ionomycin-induced phosphorylation of hemagglutinin (HA)-CaMKI alpha at Thr177, HA-CaMKIV at Thr196, and HA-AMPK alpha at Thr172 in transfected cells was significantly suppressed by cotransfection of kinase-dead mutants of CaMKK isoforms, but these dominant-negative effects were abrogated with RP-deletion mutants, suggesting that sequestration of substrate kinases by loss-of-function CaMKK mutants requires the RP-domain. This was confirmed by pulldown experiments that showed that dominant-negative mutants of CaMKK alpha and CaMKK beta interact with target kinases but not RP-deletion mutants. Taken together, these results clearly indicate that both CaMKK isoforms require the RP-domain to recognize downstream kinases to interact with and phosphorylate Thr residues in their activation loops. Thus, the RP-domain may be a promising target for specific CaMKK inhibitors. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0942-2056 30 11 2022 Increased cleft width during knee flexion is useful for the diagnosis of medial meniscus posterior root tears 3726 3732 EN Takaaki Hiranaka Department of Orthopaedic Surgery, Okayama University Hospital Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Hospital Shinichi Miyazawa Department of Orthopaedic Surgery, Okayama University Hospital Keisuke Kintaka Department of Orthopaedic Surgery, Okayama University Hospital Naohiro Higashihara Department of Orthopaedic Surgery, Okayama University Hospital Masanori Tamura Department of Orthopaedic Surgery, Okayama University Hospital Ximing Zhang Department of Orthopaedic Surgery, Okayama University Hospital Haowei Xue Department of Orthopaedic Surgery, Okayama University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Hospital Purpose<br> This study aimed to evaluate changes in the cleft width, defined as the distance between the lateral edge of the medial tibial plateau and that of the medial meniscus (MM) posterior root, using open magnetic resonance imaging (MRI) in patients with MM posterior root tear (MMPRT).<br> <br> Methods<br> This study included 25 patients (20 women and 5 men; mean age: 65.2 years) who were diagnosed with MMPRT and underwent pullout repair. Upon coronal imaging, the cleft width was evaluated at the 10° and 90° flexed knee positions. The difference in the cleft width (defined as the cleft width at 90° minus the cleft width at 10°) was also calculated. Upon sagittal imaging, the MM posterior extrusion (MMPE) at 90° was also evaluated. Separate univariate linear regression models were used to determine the association between the time from injury to MRI and radiographic measurements.<br> <br> Results<br> The mean cleft width at 10° and 90° was 4.9 ± 2.6 mm and 7.4 ± 3.7 mm, respectively; the mean difference in cleft width was 2.5 ± 1.5 mm, and the mean MMPE at 90° was 3.7 ± 1.3 mm. There was a significant difference in cleft width at 10° and 90° (p < 0.001). The time from injury to MRI was significantly associated with the cleft width at 10° (R = 0.42; p = 0.023), cleft width at 90° (R = 0.59; p = 0.002), the difference in the cleft width (R = 0.62; p = 0.008), and MMPE at 90° (R = 0.53; p = 0.008).<br> <br> Conclusion<br> This study demonstrates that the cleft width is significantly larger during knee flexion than during knee extension. Increased cleft width during knee flexion (“graben” sign) may help diagnose MMPRT, especially in cases where the cleft sign is unclear during knee extension. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0006-2960 61 7 2022 Conformation-Dependent Reversible Interaction of Ca2+/Calmodulin-Dependent Protein Kinase Kinase with an Inhibitor, TIM-063 545 553 EN Satomi Ohtsuka Applied Cell Biology, Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University Taisei Okumura Department of Science Education, Graduate School of Education, Okayama University Yuna Τabuchi Department of Science Education, Graduate School of Education, Okayama University Tomoyuki Miyagawa Department of Science Education, Graduate School of Education, Okayama University Naoki Kanayama Applied Cell Biology, Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University Masaki Magari Applied Cell Biology, Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University Naoya Hatano Applied Cell Biology, Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University Hiroyuki Sakagami Department of Anatomy, Kitasato University School of Medicine Futoshi Suizu Division of Cancer Biology, Institute for Genetic Medicine, Hokkaido University Teruhiko Ishikawa Department of Science Education, Graduate School of Education, Okayama University Hiroshi Tokumitsu Applied Cell Biology, Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University Ca2+/calmodulin-dependent protein kinase kinase (CaMKK), a Ca2+/CaM-dependent enzyme that phosphorylates and activates multifunctional kinases, including CaMKI, CaMKIV, protein kinase B/Akt, and 5'AMP-activated protein kinase, is involved in various Ca2+-signaling pathways in cells. Recently, we developed an ATP competitive CaMKK inhibitor, TIM-063 (2-hydroxy-3-nitro-7H-benzo-[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one, Ohtsuka et al. Biochemistry 2020, 59, 1701-1710). To gain mechanistic insights into the interaction of CaMKK with TIM-063, we prepared TIM-063-coupled sepharose (TIM-127-sepharose) for association/dissociation analysis of the enzyme/inhibitor complex. CaMKK alpha/beta in transfected COS-7 cells and in mouse brain extracts specifically bound to TIM-127-sepharose and dissociated following the addition of TIM-063 in a manner similar to that of recombinant GST-CaMKK alpha/beta, which could bind to TIM-127sepharose in a Ca2+/CaM-dependent fashion and dissociate from the sepharose following the addition of TIM-063 in a dose dependent manner. In contrast to GST-CaMKK alpha, GST-CaMKK beta was able to weakly bind to TIM-127-sepharose in the presence of EGTA, probably due to the partially active conformation of recombinant GST-CaMKK beta without Ca2+/CaM-binding. These results suggested that the regulatory domain of CaMKK alpha prevented the inhibitor from interacting with the catalytic domain as the GST-CaMKK alpha mutant (residues 126-434) lacking the regulatory domain (residues 438-463) interacted with TIM-127-sepharose regardless of the presence or absence of Ca2+/CaM. Furthermore, CaMKK alpha bound to TIM-127-sepharose in the presence of Ca2+/ CaM completely dissociated from TIM-127-sepharose following the addition of excess EGTA. These results indicated that TIM-063 interacted with and inhibited CaMKK in its active state but not in its autoinhibited state and that this interaction is likely reversible, depending on the concentration of intracellular Ca2+. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0179-1613 128 2022 Artificial selections for death-feigning behavior in beetles show correlated responses in amplitude of circadian rhythms, but the period of the rhythm does not 453 460 EN Takahisa Miyatake Graduate School of Environmental and Life Science, Okayama University Masato S. Abe Center for Advanced Intelligence Project, RIKEN Kentarou Matsumura Laboratory of entomology, Faculty of Agriculture Taishi Yoshii Graduate School of Natural Science and Technology, Okayama University One of the most important survival strategies of organisms is to avoid predators. Studying one of such strategies, namely, death-feigning behavior, has recently become more common. The success or failure of this antipredator strategy will be affected by the circadian rhythms of both prey and predator because death feigning sometimes has a diurnal rhythm. However, few studies have analyzed the effects of differences in circadian rhythms on predator-avoidance behavior at the genetic level. Recently, the relationship between genes relating to circadian rhythm and death-feigning behavior, an antipredator behavior, has been established at the molecular level. Therefore, in this study, we compared three circadian rhythm-related traits, the free-running period of rhythms, amplitude of circadian rhythms, and total activity of strains of three Tribolium species that were artificially selected for the death-feigning duration: short (S-strains) and long (L-strains) durations. As a result, the amplitude of circadian rhythms and total activity were significantly different between S- and L-strains, but there was no difference in the free-running periods of the rhythm between the strains in T. castaneum, T. confusum, and T. freemani. Although the relationship between death-feigning behavior and activity has been reported for all three species, a genetic relationship between the duration of death feigning and the amplitude of circadian rhythms has been newly found in the present study. It is important to investigate the relationship between antipredator strategies and circadian rhythms at the molecular level in the future. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2161-3915 33 9 2022 Minimizing the monetary penalty and energy cost of server migration service e4511 EN Yukinobu Fukushima The Graduate School of Natural Science and Technology, Okayama University Tatsuya Suda University Netgroup Inc. Tutomu Murase Information Technology Center, Nagoya University Yuya Tarutani The Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tokumi Yokohira The Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Current IaaS (Infrastructure as a Service) cloud service may not satisfy communication QoS (Quality of Service) requirements of delay-sensitive network applications, if there is a significant physical distance between a server of the network application (NetApp server) at a data center and its network application clients (NetApp clients). In order to improve communication QoS of NetApp clients, we propose Server Migration Service (SMS) in this paper. SMS allowsNetApp servers to migrate among different locations in the network (1) to optimally locate themselves in relation to NetApp clients and mitigate the QoS degradation caused by location-related factors (i.e., propagation delays on network links) and (2) to optimally distribute traffic load over routers and processing load over (physical) computers and decrease the energy consumption. We develop a mixed-integer programming model that determines when and to which locations NetApp servers migrate to minimize the total operating cost of SMS, i.e., the sum of the monetary penalty incurred due to QoS violation and energy cost incurred due to energy consumption, while preventing NetApp servers from excessively migrating and adversely impacting QoS of the non-SMS service that share the resource of the substrate network with SMS. Simulation results show that the model developed in this paper achieves up to 42% lower total operating cost of SMS compared to the model that only minimizes the monetary penalty of SMS without considering the energy cost of SMS. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1433-7398 39 2022 Implications of immune cells in oncolytic herpes simplex virotherapy for glioma 57 64 EN Yoshihiro Otani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ji Young Yoo Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston Toshihiko Shimizu Department of Neurosurgery, Matsuyama Shimin Hospital Kazuhiko Kurozumi Department of Neurosurgery, Hamamatsu University School of Medicine Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Balveen Kaur Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston Despite current progress in treatment, glioblastoma (GBM) remains a lethal primary malignant tumor of the central nervous system. Although immunotherapy has recently achieved remarkable survival effectiveness in multiple malignancies, none of the immune checkpoint inhibitors (ICIs) for GBM have shown anti-tumor efficacy in clinical trials. GBM has a characteristic immunosuppressive tumor microenvironment (TME) that results in the failure of ICIs. Oncolytic herpes simplex virotherapy (oHSV) is the most advanced United States Food and Drug Administration-approved virotherapy for advanced metastatic melanoma patients. Recently, another oHSV, Delytact®, was granted conditional approval in Japan against GBM, highlighting it as a promising treatment. Since oncolytic virotherapy can recruit abundant immune cells and modify the immune TME, oncolytic virotherapy for immunologically cold GBM will be an attractive therapeutic option for GBM. However, as these immune cells have roles in both anti-tumor and anti-viral immunity, fine-tuning of the TME using oncolytic virotherapy will be important to maximize the therapeutic efficacy. In this review, we discuss the current knowledge of oHSV, with a focus on the role of immune cells as friend or foe in oncolytic virotherapy. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0140-7791 45 2022 Three highly conserved hydrophobic residues in the predicted α2‐helix of rice NLR protein Pit contribute to its localization and immune induction 1876 1890 EN Qiong Wang School of Horticulture and Plant Protection Yangzhou University Yangzhou China Yuying Li CAS Center for Excellence in Molecular Plant Sciences, Shanghai Center for Plant Stress Biology Chinese Academy of Sciences Shanghai China Ken‐ichi Kosami CAS Center for Excellence in Molecular Plant Sciences, Shanghai Center for Plant Stress Biology Chinese Academy of Sciences Shanghai China Chaochao Liu School of Biotechnology Jiangsu University of Science and Technology Zhenjiang China Jing Li CAS Center for Excellence in Molecular Plant Sciences, Shanghai Center for Plant Stress Biology Chinese Academy of Sciences Shanghai China Dan Zhang School of Horticulture and Plant Protection Yangzhou University Yangzhou China Daisuke Miki CAS Center for Excellence in Molecular Plant Sciences, Shanghai Center for Plant Stress Biology Chinese Academy of Sciences Shanghai China Yoji Kawano Institute of Plant Science and Resources, Okayama University Nucleotide-binding leucine-rich repeat (NLR) proteins work as crucial intracellular immune receptors. N-terminal domains of NLRs fall into two groups, coiled-coil (CC) and Toll-interleukin 1 receptor domains, which play critical roles in signal transduction and disease resistance. However, the activation mechanisms of NLRs, and how their N-termini function in immune induction, remain largely unknown. Here, we revealed that the CC domain of a rice NLR Pit contributes to self-association. The Pit CC domain possesses three conserved hydrophobic residues that are known to be involved in oligomer formation in two NLRs, barley MLA10 and Arabidopsis RPM1. Interestingly, the function of these residues in Pit differs from that in MLA10 and RPM1. Although three hydrophobic residues are important for Pit-induced disease resistance against rice blast fungus, they do not participate in self-association or binding to downstream signalling molecules. By homology modelling of Pit using the Arabidopsis ZAR1 structure, we tried to clarify the role of three conserved hydrophobic residues and found that they are located in the predicted α2-helix of the Pit CC domain and involved in the plasma membrane localization. Our findings provide novel insights for understanding the mechanisms of NLR activation as well as the relationship between subcellular localization and immune induction. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 2 2022 A Case of Primary Osteosarcoma of the Mandible That Responded to Preoperative Chemotherapy: p16 as a Potential Prognostic Factor 229 233 EN Takashi Kono Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Nobuya Monden Division of Head and Neck Surgery, National Hospital Organization Shikoku Cancer Center Nobuyuki Chikuie Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Takayuki Taruya Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Takao Hamamoto Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Takashi Ishino Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Tsutomu Ueda Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Sachio Takeno Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Case Report 10.18926/AMO/63428 We report a case of mandibular osteosarcoma in a Japanese woman in her 70s who was p16-positive. Despite the rapid growth of the tumor, the patient responded well to chemotherapy and was then able to undergo surgery. Head and neck osteosarcoma (HNOS) is a very rare cancer, and although the importance of surgery has been pointed out, the effectiveness of chemotherapy is unclear. Resection margin negativity and response to chemotherapy have been reported as prognostic factors; another report assessed the effectiveness of the immunohistochemical expression of p16 protein as a predictor of response to chemotherapy. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1735-1472 2022 Fuel spray impingement and liquid film formation in a gasoline direct-injection spark-ignition engine EN Yasutaka Tomomatsu Graduate School of Natural Science and Technology, Okayama University Nobuyuki Kawahara Graduate School of Natural Science and Technology, Okayama University Eiji Tomita Graduate School of Natural Science and Technology, Okayama University It is important to improve the thermal efficiency and reduce the harmful exhaust emissions of the direct-injection spark-ignition engine. However, this engine has problems such as the emission of particulate matter, including soot, from pool fire with luminous flames. Pool fire is caused by the thermal decomposition of a liquid film, which is created by fuel spray impinging on a piston surface. An understanding of liquid film formation process is important to reduce particulate matter. The purpose of this investigation was to evaluate the effects of injection pressure on fuel spray impingement and liquid film formation process, under engine motoring conditions, using the laser-induced fluorescence method. The fuel consisted of isooctane, 1-octanol and rhodamine B. 1-Octanol was the solvent for rhodamine B, which was illuminated with a neodymium-doped yttrium aluminum garnet laser, causing it to emit red fluorescence at a wavelength of 580 nm; the second harmonic of the laser is at 532 nm. Liquid film images were captured using a high-speed camera. Using image processing, the liquid film area, thickness and mass were estimated. It was found that increasing injection pressure increased the liquid film area, thinned the film and decreased the mass of fuel that remained. In total, 35.6% and 32.5% of the injection mass remained on the piston surface at an injection pressure of 5 and 13 MPa, respectively. In addition, the in-cylinder flow affected the liquid film formation process, stretching the film in the direction of the flow. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0304-8608 167 4 2022 A novel deltapartitivirus from red clover 1201 1204 EN Paul Telengech Institute of Plant Science and Resources, Okayama University Sabitree Shahi Institute of Plant Science and Resources, Okayama University Hideki Kondo Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University The family Partitiviridae has five genera, among which is the genus Deltapartitivirus. We report here the complete genome sequence of a deltapartitivirus from red clover, termed “red clover cryptic virus 3” (RCCV3). RCCV3 has a bisegmented double-stranded (ds) RNA genome. dsRNA1 and dsRNA2 are 1580 and 1589 nucleotides (nt) in length and are predicted to encode an RNA-directed RNA polymerase (RdRP) and a capsid protein (CP), respectively. The RCCV3 RdRP shares the highest sequence identity with the RdRP of a previously reported deltapartitivirus, Medicago sativa deltapartitivirus 1 (MsDPV1) (76.5%), while the RCCV3 CP shows 50% sequence identity to the CP of MsDPV1. RdRP- and CP-based phylogenetic trees place RCCV3 into a clade of deltapartitiviruses. The sequence and phylogenetic analyses clearly indicate that RCCV3 represents a new species in the genus Deltapartitivirus. RCCV3 was detectable in all three tested cultivars of red clover. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2059-8521 7 2022 Dense immobilization of gold nanoparticles onto a cotton textile for obtaining plasmonic heating 405 409 EN Nobuko Fukuda Graduate School of Environmental and Life Science, Okayama University Naoyuki Ishida Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University Cotton textiles with plasmonic functions were obtained by dense immobilization of gold nanoparticles (AuNPs) performed by reduction of tetrachoroaurate (III) ion electrostatically adsorbed on the cotton fibers. Polyethyleneimine (PEI) adsorbed on the cotton fibers supports dense adsorption of tetrachloroaurate (III) ions, and the subsequent reduction with trisodium citrate provides dense AuNPs. The resulting cotton textile immobilized with AuNPs performed heating by irradiation of continuous visible light based on a plasmonic photothermal effect. No potential conflict of interest relevant to this article was reported.