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

Elsevier BV Acta Medica Okayama 0143-4160 135 2026 Regulation of brain-specific kinases 1 and 2 (BRSK1/2) by Ca2+/calmodulin 103134 EN Naoyuki Washida Moe Kataoka Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Anna R. Brun Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Uryu Takezaki Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ko Hijikawa Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Haruki Yamauchi Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Satomi Ohtsuka Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masaki Magari Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ryo Morishita CellFree Sciences Co., Ltd. Hiroshi Tokumitsu Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University We conducted a genome-wide calmodulin (CaM) interaction screening of 462 GST-fused human protein kinases to identify novel CaM-dependent protein kinases (CaMKs). In addition to known CaMKs, including myosin light chain kinases, CaMK2ƒΑ, and death-associated kinase 2, we identified the brain-specific protein kinase 2 (BRSK2, also known as SAD-A) as a novel CaM interactant. Proximity biotinylation and CaM–sepharose chromatography assays revealed that rat BRSK isoforms (BRSK1/2) interact with CaM in a Ca2+-dependent manner in vitro. We found that CaM suppresses the activation-loop phosphorylation of BRSK1 (at Thr189) and BRSK2 (at Thr175) by liver kinase B1 (LKB1), an activating kinase, in a Ca2+-dependent manner (IC50 of ∼7 µM), thereby inhibiting BRSK activation. LKB1-catalyzed phosphorylation of the catalytic domain mutant of BRSK1 (residues 1–294) at Thr189 was suppressed by the addition of Ca2+/CaM, consistent with direct CaM binding of the kinase domain, as well as wild-type BRSK1. We confirmed that the LKB1 activity was not directly suppressed by Ca2+/CaM, supporting the hypothesis that the direct interaction of Ca2+/CaM with the kinase domain blocks the phosphorylation/activation of BRSK1/2 by LKB1. The kinase activity and PP2CƒΏ-catalyzed dephosphorylation of LKB1-phosphorylated BRSK1 were not altered by Ca2+/CaM, although it was demonstrated to bind to Ca2+/CaM like that of unphosphorylated BRSK1. This unrecognized mechanism of BRSK1/2 regulation, involving the direct role of Ca2+/CaM binding, which inhibits phosphorylation/activation by LKB1, may open a new Ca2+ signal transduction pathway in neurons. No potential conflict of interest relevant to this article was reported.

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

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

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

Springer Science and Business Media LLC Acta Medica Okayama 0021-5155 2026 Real-world six-month outcomes after switching from aflibercept 2 mg to aflibercept 8 mg for neovascular age-related macular degeneration EN Hiroya Kindo 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 Chihiro Ouchi 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 Tetsuro Morita Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junko Hayashi 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 6-month outcomes in eyes with neovascular age-related macular degeneration (nAMD) switched from intravitreal aflibercept 2 mg to intravitreal aflibercept 8 mg.<br> Study design Retrospective observational study.<br> Methods We reviewed records of consecutive nAMD eyes switched from aflibercept 2 mg to 8 mg. In eyes continuing aflibercept 8 mg, best-corrected visual acuity (BCVA), treatment intervals, and anatomical/exudative parameters were evaluated at 6 months. In eyes that could not continue, reasons for discontinuation were examined.<br> Results Forty-four eyes from 44 patients were included. At 6 months, 35 eyes (79.5%) continued and 9 (20.5%) discontinued aflibercept 8 mg. Discontinuing eyes had significantly shorter pre-switch treatment intervals and more frequent prior therapies than continuing eyes. In the continuation group, BCVA remained stable (median 0.05 to 0.00 logMAR, P = 0.351), while the treatment interval was significantly extended (median 7.0 to 9.0 weeks, P < 0.001). Central retinal thickness and pigment epithelial detachment height decreased significantly (P = 0.035 and P = 0.021, respectively). The proportion of eyes with subretinal fluid significantly decreased from 74.3 to 37.1% (P = 0.003). Of the discontinuations, 4 were due to worsening exudation and 5 to inability to extend to ≥8 weeks as required by labeling. No intraocular inflammation or serious adverse events occurred.<br> Conclusions Switching to aflibercept 8 mg achieved anatomical improvements and longer treatment intervals in ~80% of nAMD cases, suggesting it may be a useful alternative to aflibercept 2 mg. However, continuation may be difficult in refractory cases requiring frequent injections before switching. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2752-4191 5 6 2025 Sex differences in the progression of cardiovascular–kidney–metabolic syndrome oeaf162 EN Satoshi Taya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidehiro Kaneko Department of Cardiovascular Medicine, The University of Tokyo Yuta Suzuki Department of Advanced Cardiology, The University of Tokyo Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Mizuno Department of Cardiology, Medical Quality Management Office, QI Center, St. Luke's International Hospital Toshiyuki Ko Department of Cardiovascular Medicine, The University of Tokyo Takahiro Jimba Department of Cardiovascular Medicine, The University of Tokyo Tatsuhiko Azegami Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine Akira Okada Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of Tokyo Katsuhito Fujiu Department of Cardiovascular Medicine, The University of Tokyo Norifumi Takeda Department of Cardiovascular Medicine, The University of Tokyo Hiroyuki Morita Department of Cardiovascular Medicine, The University of Tokyo Kaori Hayashi Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine Koichi Node Department of Cardiovascular Medicine, Saga University Masaomi Nangaku Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine Hideo Yasunaga Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo Norihiko Takeda Department of Cardiovascular Medicine, The University of Tokyo Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aims Cardiovascular–kidney–metabolic (CKM) syndrome is a novel disease concept; however, sex differences in its progression remain uncertain. This study aimed to quantify the risk of cardiovascular disease (CVD) events across CKM stages and to explore sex differences in this association.<br> Methods and results We included 1 332 436 individuals (581 423 males and 751 013 females) from the DeSC database between 2014 and 2023 who had no prior CVD (i.e. CKM Stage 4). CKM stages were categorized as follows: Stage 0 (no CKM risk factors); Stage 1 (excess or dysfunctional adiposity); Stage 2 [metabolic risk factors and chronic kidney diseases (CKD)], and Stage 3 (subclinical CVD). We used Cox models to examine the association of CKM stages with the risk of CVD events (newly developed CKM Stage 4), including myocardial infarction, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The progression from CKM Stages 0 to 3 showed a dose-dependent increase in adjusted hazard ratios (HR) for developing CVD events, with the highest risk at Stage 3 [1.85 (95% CI: 1.80–1.90)]. A similar pattern was observed in both males and females. However, the magnitude of associations for CKM stages 1–3 differed between the sexes: HR by Stage 1, 1.12 (1.04–1.21) vs. 1.12 (1.07–1.16); by Stage 2, 1.78 (1.69–1.88) vs. 1.43 (1.39–1.48); by Stage 3, 1.99 (1.89–2.10) vs. 1.82 (1.76–1.88); and P-for-interaction values were 0.87, < 0.001, and 0.005, respectively.<br> Conclusion In this large nationwide cohort, CKM stage progression was associated with higher CVD risk in both sexes, with modest sex-specific differences. These findings highlight the value of CKM staging for early risk assessment, regardless of sex. No potential conflict of interest relevant to this article was reported.

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

MDPI AG Acta Medica Okayama 2076-2615 16 3 2026 Impact of the July 2018 Heavy Rain Disaster on the Endangered Nagoya Daruma Pond Frog (Pelophylax porosus brevipodus) in Rice Fields of Mabi Town, Kurashiki City, Western Japan: Changes in Population Structure over Five Years 369 EN Ryo Nakajima Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Daisuke Azumi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Masakazu Tada Okayama Prefectural Public Interest Incorporated Foundation for Environmental Conservation Junya Nakaichi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koki R. Katsuhara Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuyoshi Nakata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Rice paddy fields (referred to below as rice fields) are important not only for food production, but also as habitats for various species. The Nagoya Daruma Pond Frog (Pelophylax porosus brevipodus) is an endangered frog species endemic to Japan, mainly living in and around rice field areas. In July 2018, heavy rainfall caused severe flooding in Mabi Town of Okayama Prefecture, western Japan, submerging numerous rice fields and affecting local frog populations, including P. porosus brevipodus. To clarify whether the population structure of P. porosus brevipodus changed following the flood disaster in the rice fields of Mabi Town, we conducted quantitative field surveys in a rice fallow field in mid-October before (2017) and after (2018, 2020–2022, excluding 2019) the flood. The number of frogs declined sharply after the 2018 flood, reaching only a few individuals by 2020, but showed a substantial recovery in 2021 following the resumption of rice cultivation, although numbers decreased again in 2022. This recovery, despite fluctuations, indicates that habitat restoration through rice farming played a key role in enabling the population to rebound. Our findings underscore the importance of maintaining and restoring rice field environments after natural disasters for the survival and long-term recovery of P. porosus brevipodus. No potential conflict of interest relevant to this article was reported.

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

Frontiers Media SA Acta Medica Okayama 1664-042X 16 2025 Activation of the pentose phosphate pathway by microcurrent stimulation mediates antioxidant effects in inflammation-stimulated macrophages 1666999 EN Mikiko Uemura Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences Noriaki Maeshige Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences Atomu Yamaguchi Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences Xiaoqi Ma Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences Yunfei Fu Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences Taketo Inoue Assisted Reproductive Technology Center, Okayama University Mami Matsuda Graduate School of Science, Technology and Innovation, Kobe University Yuya Nishimura Graduate School of Science, Technology and Innovation, Kobe University Tomohisa Hasunuma Graduate School of Science, Technology and Innovation, Kobe University Ji Wang Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University Hiroyo Kondo Department of Nutrition, Faculty of Health and Nutrition, Shubun University Hidemi Fujino Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences Introduction: Excessive inflammatory responses in macrophages lead to increased oxidative stress, and the excessive production of reactive oxygen species (ROS) causes tissue damage, contributing to the development of chronic diseases and tissue deterioration. Therefore, controlling the inflammatory response and ROS production is crucial for human health. Electrical stimulation (ES) has been shown to have antioxidant and anti-inflammatory effects on macrophages. However, the key pathway underlying these effects remains unclear.<br> Methods: In this study, ES was applied to Lipopolysaccharide (LPS)-stimulated macrophages, and the production of ROS and 8–hydroxy–2Œ–deoxyguanosine (8-OHdG), inflammatory cytokine expression, and intracellular metabolites were analyzed in a glucose-6-phosphate dehydrogenase (G6PD) knockdown experiment, the rate-limiting enzyme of the Pentose Phosphate Pathway(PPP).<br> Results: ES significantly increased sedoheptulose 7-phosphate (S7P), an intermediate metabolite in PPP, and reduced ROS and 8-OHdG production and the expression of inflammatory cytokines in LPS-stimulated macrophages. Meanwhile, ES did not exert antioxidant effects in G6PD-knockdown macrophages.<br> Discussion: These findings indicate that the antioxidant effects of ES are mediated by PPP in LPS-stimulated macrophages. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1472-6831 25 1 2025 Evaluation of Streptococcus mutans strains possessing genes encoding collagen-binding proteins in the Japanese population 1908 EN Makoto Okuda Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka Yuto Suehiro Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka Jinthana Lapirattanakul Department of Oral Microbiology, Faculty of Dentistry, Mahidol University Shuhei Naka Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Michiyo Matsumoto-Nakano Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryota Nomura Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University Rena Okawa Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka Kazuhiko Nakano Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka Background Streptococcus mutans harbors collagen-binding protein genes, namely cnm and cbm, which are implicated in its virulence and pathogenicity in both oral and extraoral infections. Although both genes were initially identified in S. mutans isolated from Japanese populations, their geographical prevalence, distribution, and genetic relatedness within Japan remain largely unexplored. This study investigates the prevalence of S. mutans strains carrying cnm and cbm genes across Japan, correlates these findings with clinical data, and analyzes the genetic relatedness of cnm-positive and cnm-negative strains using multilocus sequence typing (MLST).<br> Methods Dental plaque specimens were collected from 1248 individuals from eight Japanese cities (Hiroshima, Fukuoka, Nagasaki, Niigata, Okayama, Osaka, Tokushima, and Tokyo) and plated on selective medium for S. mutans isolation. S. mutans was confirmed in 523 subjects by colony morphology and PCR using species-specific primers, and the presence of the cnm and cbm genes was determined by PCR with gene-specific primers. Demographic (age, sex) and oral examination (caries prevalence, caries experience, number of teeth) data were recorded. MLST was employed to genotype selected cnm-positive and cnm-negative S. mutans strains to assess their clonal relationships.<br> Results Among 523 subjects possessing S. mutans (aged 3–90 years), we detected cnm-positive strains in all cities; specifically, the prevalence ranged from 5.5% in Okayama to 25.0% in Tokushima. In contrast, cbm-positive strains were less common and undetectable in some regions. Furthermore, subjects harboring cnm-positive S. mutans were significantly older (p = 0.002) and had higher caries prevalence and experience (p < 0.001). MLST revealed evolutionary relationships among cnm-positive strains across the cities but no discernible region-specific clustering. Clonal relationships partially reflected cnm gene distribution, particularly for exclusively cnm-positive or cnm-negative clonal complexes, but inconsistencies involving serotypes and cnm presence within some clonal complexes and sequence types were also noted.<br> Conclusions The cnm-positive S. mutans strains are widely distributed throughout Japan and are associated with increased age and caries burden. Although core genome analysis revealed some clonal patterns, the non-uniform distribution of the non-core cnm gene is likely influenced by horizontal gene transfer, providing S. mutans with adaptive advantages irrespective of its core genetic background or serotype. No potential conflict of interest relevant to this article was reported.

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

Fuji Technology Press Ltd. Acta Medica Okayama 1883-8049 37 6 2025 Directed Poisoning Attacks on FRIT in Adaptive Cruise Control 1392 1399 EN Taichi Ikezaki Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kenji Sawada Graduate school of Mechanical Engineering, The University of Osaka Osamu Kaneko Graduate School of Informatics and Engineering, The University of Electro-Communications Recent advances in connected-vehicle technologies have enabled the large-scale collection of driving data, facilitating the deployment of data-driven control schemes. Although these methods offer advantages by eliminating the need for explicit modeling, they also introduce vulnerabilities due to their reliance on stored data. This study investigates a class of targeted data poisoning attacks on fictitious reference iterative tuning, a widely used data-driven controller tuning approach. We present a method that allows an adversary to influence closed-loop dynamics by manipulating the training data so that the resulting controller behavior matches a maliciously defined reference response. This strategy differs from conventional poisoning attacks, which aim only to the degrade control performance. Instead, it enables deliberate alteration of control characteristics such as overshoot and convergence time. The proposed attack is formulated as a constrained optimization problem under bounded tampering signals. Through a numerical study involving adaptive cruise control with stop functionality, we show that minor data modifications, indistinguishable from sensor noise, can cause significant degradation in control behavior. These findings highlight the need for robust security mechanisms in data-driven control implementation. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 1468-0874 2025 Effects of size factors and velocity of impinging diesel spray flames on wall heat transfer EN Yoshimitsu Kobashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ryoga Hirai Graduate School of Engineering, Hokkaido University Gen Shibata Graduate School of Engineering, Hokkaido University Hideyuki Ogawa Graduate School of Engineering, Hokkaido University To examine the effects of size and velocity of impinging diesel spray flames on wall heat transfer, this study conducted visualization of the spray flame and measurements of wall heat flux in a constant volume vessel. The impinging flame velocity was varied by adjusting the injection velocity. To vary the flame size independently of the flame velocity, the nozzle orifice diameter and the nozzle-to-wall distance were varied under similarity conditions, while maintaining a constant ratio of nozzle-to-wall distance to orifice diameter. Care was taken to minimize wall interference from the liquid phase and unburned regions of the spray flame by employing a high cetane number fuel and increasing the nozzle-to-wall distance. The experimental results showed that the wall heat flux increased as the impinging velocity increased, and the flame width decreased. The power-law correlations between the Nusselt and Reynolds numbers were determined based on the experimental results, revealing that the exponent of the Reynolds number reaches a local minimum at the impingement point. As the radial displacement from the impingement point increases, the exponent of the Reynolds number approaches approximately 0.8, which is a typical value for turbulent wall flow. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Effects of Thoron Inhalation and Cyclosporin A Treatment on Dextran Sulfate Sodium-Induced Oxidative Damage in Mice 421 429 EN Ayumi Tanaka Graduate School of Health Sciences, Okayama University Shota Naoe Graduate School of Health Sciences, Okayama University Reiju Takenaka Graduate School of Health Sciences, Okayama University Norie Kanzaki Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Akihiro Sakoda Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Takahiro Kataoka Faculty of Health Sciences, Okayama University Original Article 10.18926/AMO/69844 Radon (222Rn; Rn) and thoron (220Rn; Tn) inhalation have been reported to enhance antioxidant activity in various organs. However, the effects of Tn on the colon have not been investigated. This study aimed to clarify the effects of Tn inhalation, alone and in combination with cyclosporin A (CsA), on dextran sulfate sodium (DSS)-induced colitis, and the accompanying oxidative stress, in mice. Male BALB/c mice were subjected to continuous 8-day Tn inhalation (c-Tn, 533}128 Bq/m3) or alternate-day Tn inhalation over the same period (f-Tn, 577}63Bq/m3), followed by treatment with 3% DSS and either CsA or vehicle for 7 days. Although the disease activity index (DAI) decreased significantly by day 2 in the c-Tn group, scores remained significantly higher than those in the f-Tn group. In the c-Tn group, superoxide dismutase and catalase activity in the colon were significantly elevated compared with those in sham controls. Thus, DSS-induced damage was effectively inhibited in the earlier stages by the c-Tn mode of inhalation than by the f-Tn mode. These findings suggest that continuous Tn inhalation more effectively attenuated early colitis symptoms than alternate-day inhalation, potentially through upregulation of antioxidant defenses. Tn and CsA showed no combined effects. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Real-World Outcomes of Anti-Vascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration in Patients Aged 85 or Older 405 412 EN Chihiro Ouchi 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 Shuhei Kimura 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 Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuro Morita Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/69842 We investigated the treatment outcomes of patients aged ≥85 years with neovascular age-related macular degeneration (nAMD) who received anti-vascular endothelial growth factor (anti-VEGF) therapy using either treat-and-extend (TAE) or pro re nata (PRN) regimens for 1 year in real-world clinical practice. Eighty-five eyes from 85 patients were included. Among them, types 1, 2, and 3 macular neovascularization and polypoidal choroidal vasculopathy were present in 27.1%, 17.6%, 18.8%, and 36.5%, respectively. TAE and PRN regimens were used in 43.5% and 56.5% of patients, respectively. At baseline, the PRN group was older and had worse best-corrected visual acuity (BCVA), greater central retinal thickness, and more intraretinal fluid than the TAE group. In the TAE group, the mean number of injections was 7.6, BCVA improved significantly, and all retinal fluid rates decreased. In the PRN group, the mean number of injections was 3.9, BCVA remained unchanged, and the rates of macular fibrosis and atrophy increased. No serious adverse events were observed in either group. Anti-VEGF therapy was safe for patients aged ≥ 85 years with nAMD, and the TAE regimen effectively improved BCVA in this population. BCVA remained unchanged in the PRN-treated patients, with baseline disease severity and/or undertreatment potentially influencing the outcomes. No potential conflict of interest relevant to this article was reported.

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

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

Acta Medica Okayama 2025 Development of a synthetic method for terpene scaffolds via stereoselective construction of quaternary carbon centers EN Naochika MATSUMARU Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Design and Synthesis of Cholesterol 24-Hydroxylase Inhibitors Using 1,3-Oxazole as a Heme-Iron Binding Group EN Yoshiteru ITO Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 ƒTƒCƒhƒvƒ‰ƒ“ƒWŒ€ν‚Ι‚¨‚―‚ιŒ€ν‰·“x‚ΜŽΐŒ±“IŒŸ“’‚ΖƒN[ƒ‰ƒ“ƒg‹Ÿ‹‹‚̍œK‰» EN Lingxiao Gao Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Coherence Generation in Atomic Cesium for Cosmic Dark Matter Detection EN JING WANG Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Outcomes of ultra-high-pressure balloon angioplasty for congenital heart disease in single-center experience EN Maiko KONDO 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 Novel treatment strategy targeting interleukin-6 induced by cancer associated fibroblasts for peritoneal metastasis of gastric cancer EN Ema MITSUI 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 Efficient diagnosis for endoscopic remission in Crohnfs diseases by the combination of three non-invasive markers EN Kensuke TAKEI 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 Changes of leucine-rich alpha 2 glycoprotein could be a marker of changes of endoscopic and histologic activity of ulcerative colitis EN Yuki AOYAMA 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 0916-9636 48 9 2025 Efficacy and safety of esaxerenone in hypertensive patients with chronic kidney disease, with or without type 2 diabetes mellitus: a pooled analysis of five clinical studies 2413 2426 EN 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 Hirohiko Motoki Department of Cardiovascular Medicine, Shinshu University School of Medicine Koichiro Kuwahara Department of Cardiovascular Medicine, Shinshu University School of Medicine Kazuomi Kario Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine Tomohiro Katsuya Katsuya Clinic Tatsuo Shimosawa Department of Clinical Laboratory, School of Medicine, International University of Health and Welfare Kenichi Tsujita Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Shoko Suzuki Data Intelligence Department, Daiichi Sankyo Co., Ltd. Tomohiro Suedomi Primary Medical Science Department, Daiichi Sankyo Co., Ltd. Takashi Taguchi Primary Medical Science Department, Daiichi Sankyo Co., Ltd. Effective management of blood pressure (BP) and albuminuria are crucial for suppressing chronic kidney disease (CKD) progression and cardiovascular risks in hypertension. This pooled analysis evaluated the antihypertensive effects, organ-protective effects, and safety of esaxerenone in hypertensive patients with CKD by integrating five clinical studies of esaxerenone. Patients were divided based on type 2 diabetes mellitus (T2DM) status (with or without T2DM) and creatinine-based estimated glomerular filtration rate (eGFRcreat) (30 to <60 and ≥60 mL/min/1.73 m2). Significant changes in morning home BP from baseline at Week 12 were observed in the overall population (mean change |12.8/ | 5.4 mmHg), T2DM subgroups ( | 12.2/ | 4.5 and |14.5/ | 7.8 mmHg), and eGFRcreat subgroups ( | 12.5/ | 4.7 and |14.0/ | 6.9 mmHg) (all P < 0.001). Bedtime home and office BP showed similar tendencies. Urine albumin-to-creatinine ratio significantly improved from baseline at Week 12 in the overall population (mean change: |55.2%), T2DM subgroups ( | 56.5% and |52.0%), and eGFRcreat subgroups ( | 54.6% and |55.4%) (all P < 0.001). N-terminal pro-B-type natriuretic peptide levels significantly decreased in the overall population (percent change: |14.1%) and subgroup without T2DM ( | 25.3%). The incidence of serum potassium ≥5.5 mEq/L was lower in the subgroup with T2DM vs without T2DM (3.1% and 11.3%), potentially related to the use of sodium–glucose cotransporter 2 inhibitors. These findings highlight the sustained BP-lowering effect of esaxerenone throughout the day in hypertensive patients with CKD, irrespective of T2DM status, and its significant reduction in albuminuria. The data support the safety and efficacy of esaxerenone in this patient population, underscoring its potential as a valuable therapeutic option. 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.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 11 2025 Long-Term Outcome of Xenon-Arc Photocoagulation for Retinopathy of Prematurity in the 1970s in Japan: Eleven Patients With 32- to 49-Year Follow-Up e97797 EN Toshihiko Matsuo Healthcare Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Nobuhiko Matsuo Ophthalmology, Okayama University Medical School Objectives: Photocoagulation or cryocautery, or their combinations, are the standard of care for retinopathy of prematurity at the recommended timing, which is based on the International Classification of Retinopathy of Prematurity. In Japan, the effectiveness of xenon-arc photocoagulation and cryocautery in retinopathy of prematurity was reported on an empirical basis first in 1968, and became the standard of care in retinopathy of prematurity in the 1970s, 10 years earlier compared with the other countries. In this study, we reported the up to 49 years visual outcome of 11 patients with retinopathy of prematurity who underwent xenon-arc photocoagulation and cryocautery in the 1970s.<br> Methods: A retrospective review was made on the medical records of 11 consecutive patients who underwent xenon-arc photocoagulation for retinopathy of prematurity in the years 1974 to 1980, and were followed up until the period from 2009 to 2025. The birthweight ranged from 865 g to 2300 g at a median of 1350 g, and the gestational age at birth ranged from 27 weeks to 36 weeks at a median of 30 weeks. The corrected gestational age at the time of photocoagulation ranged from 32 weeks to 53 weeks, with a median of 37 weeks. Oxygen was given to all 11 patients, except for one who was born in the earliest year 1974. The retinopathy of prematurity was at stage 3 in both eyes of seven patients, with plus disease signs in four patients, at stage 2 with and without plus disease in two patients, at stage 2 and stage 3 in each eye of one patient, and at stage 1 with plus disease in both eyes of one patient. The entire 360-degree photocoagulation was given in seven patients, while partial photocoagulation was applied in four patients. Additional cryocautery was applied in six patients.<br> Results: The age at the last visit ranged from 32 to 49 years with a median of 46 years. At the last visit, seven patients showed the best-corrected visual acuity in decimals of 0.8 or better in both eyes. One dizygotic twin showed no light perception in the phthisic right eye and 0.1 in the left eye with macular degeneration and nystagmus after he underwent cataract surgery at the age of 34 years. The other twin had the best-corrected visual acuity of 0.5 in the right eye and 0.02 in the left eye due to macular degeneration after he underwent cataract surgeries in both eyes at the age of 36 years. Two patients developed rhegmatogenous retinal detachment in one eye at the age of 44 and 41 years, respectively, and underwent vitrectomy with silicone oil tamponade, resulting in visual acuity of 0.1 and 0.3, respectively. Two patients experienced vitreous hemorrhage in one eye, which was absorbed spontaneously at the ages of 37 years and 42 years, respectively. One patient underwent partial scleral buckling for localized rhegmatogenous retinal detachment. No patient used intraocular pressure-lowering eyedrops.<br> Conclusion: Most patients with xenon-arc photocoagulation for retinopathy of prematurity in the 1970s maintained standard levels of visual acuity up to 49 years in the follow-up. Cataract, retinal detachment, and vitreous hemorrhage were noted as late complications and were coped with on an individual basis. The conclusion would have a meaning, even though not novel, that the patients with retinopathy of prematurity would have benefited from the xenon-arc photocoagulation and cryocautery. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1999-4923 17 11 2025 Development of Propofol-Encapsulated Liposomes and the Effect of Intranasal Administration on Bioavailability in Rabbits 1446 EN Hitomi Ujita Department of Dental Anesthesiology, Okayama University Hospital Hitoshi Higuchi Department of Dental Anesthesiology, Okayama University Hospital Yukiko Nishioka Department of Dental Anesthesiology, Okayama University Hospital Saki Miyake Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate of Medicine, Dentistry and Pharmaceutical Sciences Riko Sato Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate of Medicine, Dentistry and Pharmaceutical Sciences Takuya Miyawaki Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate of Medicine, Dentistry and Pharmaceutical Sciences Background/Objectives: Propofol is frequently used as an intravenous anesthetic and is rapidly metabolized. Therefore, if it could be administered non-invasively (e.g., orally) as premedication, it might hasten emergence from anesthesia, thereby improving patient safety. However, it undergoes extensive first-pass metabolism in the liver and intestines, limiting the route for premedication. We evaluated whether intranasal delivery of a propofol-encapsulated liposome solution improves systemic exposure and bioavailability in rabbits. Methods: A propofol-encapsulated liposome solution was administered to rabbits via the intravenous, oral, and intranasal routes. Blood propofol concentrations were measured for up to 60 min after administration and the area under the concentration–time curve (AUC0–60) and bioavailability of the propofol-encapsulated liposome solution were compared with those of the non-encapsulated propofol formulation. The differences were tested by two-way analysis of variance (ANOVA) with Šidákfs post hoc multiple-comparisons test and the Mann–Whitney test (ƒΏ = 0.05). Results: The AUC0–60 for blood propofol concentrations after intravenous administration was significantly higher with the propofol-encapsulated liposome solution than with the non-encapsulated propofol formulation (3038.8 } 661.5 vs. 1929.8 } 58.2 ng·min/mL; p = 0.0286). By contrast, no increase in blood propofol concentrations was observed after oral administration, whereas intranasal administration increased blood propofol concentrations and yielded significantly higher bioavailability compared with the non-encapsulated propofol formulation (16.4 } 7.3% vs. 2.0 } 1.2%; p = 0.0286). Conclusions: The findings of the present study suggest that intranasal liposomal propofol increased systemic availability compared with a non-encapsulated formulation, supporting further evaluation as a candidate premedication approach for propofol. No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 9 2025 The Intranasal Administration of Semaphorin 3A Inhibitor in a Mouse Model of Olfactory Disorder e92587 EN Aya Murai Otolaryngology - Head and Neck Surgery, Okayama University Hospital Minori Noda Otolaryngology - Head and Neck Surgery, Okayama University Hospital Aiko Shimizu Otolaryngology - Head and Neck Surgery, Okayama University Hospital Junko Takahara Division of Technical Support for Medical Science, Department of Comprehensive Technical Solutions, Okayama University Seiichiro Makihara Otolaryngology - Head and Neck Surgery, Okayama University Hospital Mizuo Ando Otolaryngology - Head and Neck Surgery, Okayama University This study investigated the effects of intranasal administration of a semaphorin 3A inhibitor (Sema3A-I) in a mouse model of olfactory disorder, where olfactory sensory neuron (OSN) axons had been severely damaged. We performed axotomy (transection of OSN axons) of the OSNs in mice and administered Sema3A‑I intranasally to seven mice and saline to another seven mice. Following treatment, we assessed the thickness of the olfactory epithelium and the regeneration ratio of OSN axons. Intranasal administration of Sema3A-I did not significantly promote OSN regeneration, axonal outgrowth, or improve axonal projection compared to saline administration. Although Sema3A-I administration showed some promotion of axonal outgrowth, the difference was not statistically significant. Continuous subcutaneous administration of Sema3A-I in rats after axotomy promotes OSN regeneration and axonal outgrowth. Given that intranasal administration is minimally invasive, we believe that it may still be a feasible route when combined with additional treatment strategies. Further investigation into administration methods and therapeutic combinations is warranted. No potential conflict of interest relevant to this article was reported.

Physical Society of Japan Acta Medica Okayama 0031-9015 94 11 2025 Magnetically Enhanced Thermoelectric Effect Driven by Martensitic Transformation in the Weak Itinerant Ferromagnet Co2NbSn 113801 EN Takumi Kihara Research Institute for Interdisciplinary Science, Okayama University Xiao Xu Department of Materials Science, Tohoku University Yuki Ogi Graduate School of Science and Engineering, Yamagata University Yoshiya Adachi Graduate School of Science and Engineering, Yamagata University Tufan Roy Center for Science and Innovation in Spintronics (CSIS), Core Research Cluster (CRC), Tohoku University Ryuji Matsuura Faculty of Engineering, Tohoku Gakuin University Takeshi Kanomata Research Institute for Engineering and Technology, Tohoku Gakuin University We investigated the magnetic and thermoelectric properties of the full Heusler alloy Co2NbSn, which exhibits a martensitic transformation at 240 K. Magnetization measurements reveal weak itinerant ferromagnetism in the martensitic phase, which is well described by Takahashifs spin fluctuation theory. The characteristic spin fluctuation parameters were estimated to be T0 = 1.0 ~ 103 K and TA = 7.2 ~ 103 K. Seebeck coefficient measurements under magnetic fields up to 9 T show complex temperature and field dependence, which we decomposed into electron diffusion, spin fluctuation drag, and magnon drag components. A significant magnon-drag contribution was identified in both austenite and martensitic phases. Remarkably, this contribution is strongly enhanced in the martensitic phase compared to the austenite phase, despite a smaller magnetic moment. These findings provide evidence for robust low-energy spin excitations and highlight the potential of martensitic transformation in enhancing the thermoelectric performance of itinerant ferromagnetic alloys. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Advantages of Single-Position Surgery over Posterior Fusion for Single-Level Degenerative Lumbar Diseases 359 368 EN Tomohiko Hirose Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital Hisanori Ikuma Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital Kazutoshi Otsuka Otsuka Orthopedic Clinic Keisuke Kawasaki Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital Original Article 10.18926/AMO/69437 Single-position surgery with lateral lumbar interbody fusion (LLIF) and percutaneous pedicle screws (PPSs) is gaining attention for its reduced invasiveness. We developed SPAPS, a technique allowing two surgeons to perform anterior LLIF and posterior PPS insertion simultaneously in a single lateral decubitus position. This retrospective study compared SPAPS (SPAPS-LLIF, Group SL) and minimally invasive posterior/transforaminal lumbar interbody fusion (MIS-PLIF/TLIF, Group PT) in patients treated between 2016 and 2019 with a two-year follow-up. Operative time, estimated blood loss (EBL), length of hospital stay (LOS), JOABPEQ and VAS scores, segmental lordotic angle, lumbar lordotic angle, segmental Cobbfs angle, PPS misplacement, PPS loosening, fusion status, and muscle cross-sectional areas were compared. Fifty-two patients were analyzed (Group SL: 25; Group PT: 27). SPAPS significantly reduced operative time (118.0 vs. 165.3 min, p <0.01) and estimated blood loss (8.6 vs. 164.1 mL, p<0.01). While clinical outcomes and hospital stay were comparable, Group SL had significantly lower PPS loosening (0% vs. 13%, p<0.01) and non-union rates (0% vs. 22.2%, p=0.02). Multifidus muscle atrophy was also less in Group SL (|14.3 vs. |121.5 mm2, p<0.01). SPAPS demonstrated advantages in reducing surgical invasiveness without compromising clinical efficacy, offering a promising alternative to conventional posterior fusion surgery. No potential conflict of interest relevant to this article was reported.

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

Frontiers Media SA Acta Medica Okayama 2624-9367 7 2025 Muscle morphological adaptations to resistance training and sports participation in children and adolescents: a scoping review 1646835 EN Shota Enomoto Institute for Promotion of Education and Campus Life, Okayama University Nobuaki Tottori Graduate School of Education, Hyogo University of Teacher Education Introduction: This scoping review aimed to systematically map the existing literature on the effects of resistance training (RT) and sports participation on muscle morphology in children and adolescents.<br> Methods: Herein, a literature search was conducted using three electronic databases: PubMed, Scopus, and Web of Science. The inclusion criteria were as follows: articles that were written in English, which used chronic RT or a combination of RT with other training methods, or investigated the effects of sports participation, and reported muscle morphology as an outcome.<br> Results: This scoping review included 29 studies: 17 cross-sectional studies, 3 prospective observational studies, and 9 interventional studies. The following distribution was obtained after categorizing the included studies according to participant age: aged 6–11 years, 12 articles; aged 12–14 years, 10 articles; and aged 15–17 years, 10 articles. The designs of interventional studies included eight quasi-experimental parallel-group trials and a quasi-experimental crossover trial. However, none of the included interventional studies followed the CONSORT guidelines for conducting randomized controlled trials. Across the included studies, 14 different sports were analyzed for their effects on muscle morphology. Four studies combined players from various sports. In the included studies, 47 different muscles or muscle groups were examined. Our results identified unexplored muscles because our included studies did not examine the volume of lower leg muscles.<br> Conclusion: Future research directions in this field, including experimental design and targeted muscles, are warranted. No potential conflict of interest relevant to this article was reported.

Fuji Technology Press Ltd. Acta Medica Okayama 1883-8022 19 5 2025 Study on an Effective Coolant Supply Method in the Side Plunge Grinding Process 939 948 EN Lingxiao Gao Graduate School of Natural Science and Technology, Okayama University Taichi Fujimoto Graduate School of Natural Science and Technology, Okayama University Hiroyuki Kodama Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kazuhito Ohashi Faculty of Environmental, Life, Natural Science and Technology, Okayama University Grinding is widely used for finishing components with journal and thrust surfaces, such as crankshafts. Side-plunge grinding enables the simultaneous finishing of thrust and cylindrical surfaces in a single plunge. However, compared to cylindrical grinding, it involves a larger contact area between the grinding wheel and the workpiece, leading to increased heat generation. In particular, poor coolant penetration near internal corners can degrade surface quality, potentially causing stress concentrations and cracks. To enhance coolant effectiveness in side-plunge grinding, this study installs a high-pressure nozzle that supplies coolant from the side of the grinding wheel. The effectiveness of this setup is experimentally verified. Additionally, the distribution of coolant flow within the contact area between the grinding wheel and the workpiece is measured to determine the optimal nozzle position for efficient coolant delivery. The nozzlefs performance is evaluated by measuring the workpiece surface temperature using a wire/workpiece thermocouple, the amount of coolant discharged from the grinding wheel, and the residual stress distribution. The results show that coolant penetrates the grinding wheel and effectively reaches the grinding zone, enhancing the cooling effect. This study clarifies the relationship between effective coolant supply and the position of the side nozzle. Considering physical constraints, such as potential interference during grinding, the optimal nozzle location is as close as possible to both the edge of the grinding wheel and the workpiece. This positioning ensures maximum coolant delivery, reduces grinding temperature, and helps suppress drastic variations in residual stress. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2041-1723 16 1 2025 Fully-gapped superconductivity with rotational symmetry breaking in pressurized kagome metal CsV3Sb5 3643 EN X. Y. Feng Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics Z. Zhao Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics J. Luo Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics Y. Z. Zhou Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics J. Yang Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics A. F. Fang H. T. Yang Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics H.-J. Gao Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics R. Zhou Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics Guo-qing Zheng Department of Physics, Okayama University The discovery of the kagome metal CsV3Sb5 has generated significant interest in its complex physical properties, particularly its superconducting behavior under different pressures, though its nature remains debated. Here, we performed low-temperature, high-pressure 121/123Sb nuclear quadrupole resonance (NQR) measurements to explore the superconducting pairing symmetry in CsV3Sb5. At ambient pressure, we found that the spin-lattice relaxation rate 1/T1 exhibits a kink at T ~ 0.4 Tc within the superconducting state and follows a T3 variation as temperature further decreases. This suggests the presence of two superconducting gaps with line nodes in the smaller one. As pressure increases beyond Pc ~ 1.85 GPa, where the charge-density wave phase is completely suppressed, 1/T1 shows no Hebel-Slichter peak just below Tc, and decreases rapidly, even faster than T5, indicating that the gap is fully opened for pressures above Pc. In this high pressure region, the angular dependence of the in-plane upper critical magnetic field Hc2 breaks the C6 rotational symmetry. We propose the s + id pairing at P > Pc which explains both the 1/T1 and Hc2 behaviors. Our findings indicate that CsV3Sb5 is an unconventional superconductor and its superconducting state is even more exotic at high pressures. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1472-6831 25 1 2025 Phosphorylated pullulan as a local drug delivery matrix for cationic antibacterial chemicals to prevent oral biofilm 1333 EN Naoko Namba-Koide Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Yasuhiro Yoshida Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Takumi Okihara Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Yusuke Kawata Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Masahiro Ito Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Takashi Ito Center for Innovative Clinical Medicine, Okayama University Hospital Kazu Takeuchi-Hatanaka Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Yuki Shinoda-Ito Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Omori Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yamamoto Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Takashiba Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Preventing oral infections, such as oral caries and periodontal disease, helps reduce the risks of various systemic diseases. In this study, the polysaccharide pullulan produced by the black yeast Aureobasidium pullulans was modified in combination with the cationic surfactant cetylpyridinium chloride (CPC) to create a local drug delivery system, and its antibacterial potential on oral bacteria was examined in vitro.<br> Methods Pullulan was phosphorylated at the CH2OH residue of ƒΏ6 in the maltotriose structure and mixed with CPC. Bacterial attachment of cariogenic Streptococcus mutans on hydroxyapatite plates (HAPs) treated with the phosphorylated pullulan (PP) and CPC compound (0.01% PP and 0.001– 0.03% CPC, and vice versa) was assessed by observing bacteria using a field emission scanning electron microscope (FE-SEM) and quantified through 16 S rRNA amplification via real-time polymerase chain reaction (PCR). Additionally, the quartz crystal microbalance (QCM) method was employed to evaluate the sustained release of CPC.<br> Results PP-CPC compound maintained significant bactericidal activity even at 0.01%, which is one-fifth of the conventional applicable concentration of CPC. Additionally, a residual mixture was detected by the hydroxyapatite sensor of the crystal oscillator microbalance detector, suggesting an unknown molecular interaction that enables the sustained release of CPC after attachment to hydroxyapatite.<br> Conclusions The combination of PP and CPC may contribute to the low concentration and effective prevention of oral infections, such as dental caries. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0014-4800 142 2025 Cross-feeding between beneficial and pathogenic bacteria to utilize eukaryotic host cell-derived sialic acids and bacteriophages shape the pathogen-host interface milieu 104967 EN Darab Ghadimi Department of Microbiology and Biotechnology, Max Rubner-Institut Regina Fölster-Holst Clinic of Dermatology, Venerology und Allergology, University Hospital Schleswig-Holstein Sophia Blömer Clinic of Dermatology, Venerology und Allergology, University Hospital Schleswig-Holstein Michael Ebsen Städtisches MVZ Kiel GmbH (Kiel City Hospital), Department of Pathology Christoph Röcken Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Shigenobu Matsuzaki Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University Wilhelm Bockelmann Department of Microbiology and Biotechnology, Max Rubner-Institut Under an inflamed-intestinal milieu, increased free sialic acids are associated with the overgrowth of some pathogenic bacterial strains. Recently, the protective immunomodulatory activity of gut bacteriophages (phages) has also been highlighted. However, the role of phages in triple reciprocal interactions between pathogenic bacteria, beneficial bacteria, and their host cell sialic acids has not been studied so far. We established a sialidase-explicit model in which beneficial and pathogenic bacteria interact through cross-feeding and competition for free sialic acid using a human triple co-culture cell model incorporating colonocytes (T84 cells), monocytes (THP-1 cells), and hepatocytes (Huh7 cells). Triple co-cultured cells were challenged with Gram-positive Bifidobacterium bifidum (B. bifidum) and Gram-negative Pseudomonas aeruginosa PAO1 (P. a PAO1) in the absence or presence of its KPP22 phage in two different cell culture mediums: 1) standard Dulbecco's Modified Eagle Medium (DMEM) and 2) DMEM with 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA). Changes in physiological, functional, and structural health markers of stimulated cocultured cells were evaluated. The concentrations of sialic acid and pro-inflammatory cytokines in the cell culture supernatants were quantified. P. a PAO1 triggered the release of interleukin 6 and 8 (IL-6 and IL-8), accompanied by increased levels of free sialic acid, reduced viability of co-cultured cells, and disrupted the integrity of the cellular monolayer. These disruptive effects were markedly attenuated by KPP22 phage and B. bifidum. In addition to well-documented differences in the structure and composition of the bacterial cell walls of Gram-negative pathogenic bacteria and bifidobacteria, two distinct factors seem to be pivotal in modulating the pathogen-host interface milieu: (i) the presence of phages and (ii) the utilization of free sialic acids secreted from host cells by bifidobacteria. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2694-2496 2025 RNA Delivery Using a Graphene Oxide-Polyethylenimine Hybrid Inhibiting Myotube Differentiation EN Koji Matsuura CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR3572, University of Strasbourg, ISIS Giacomo Reina CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR3572, University of Strasbourg, ISIS Zhengfeng Gao CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR3572, University of Strasbourg, ISIS Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Alberto Bianco CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR3572, University of Strasbourg, ISIS Graphene oxide (GO) conjugated with short polyethylenimine (PEI) chains (GO-PEI) has been designed as a candidate nanocarrier for small interfering RNA (siRNA) delivery to mammalian cells based on the efficient interaction between the positively charged GO-based platform and the negatively charged siRNA. The function and efficiency of siRNA delivery using GO-PEI were compared to those using the positive control Lipofectamine RNAiMax by analyzing the differentiation to myotubes, and myogenin gene and protein expression in C2C12 cells. RNAiMax transfection induced cellularization and reduction of both myogenin gene and protein expression, suggesting that the differentiation of C2C12 cells was triggered by gene silencing. While GO-PEI also promoted cellularization, the myogenin gene expression remained comparable to scrambled controls, whereas the protein levels were higher than those observed with RNAiMax. Mechanistically, we attributed the reduced gene silencing efficiency of GO-PEI to a poor endosomal escape, despite strong siRNA complexation. This limitation was likely due to a low buffering capacity of GO-PEI, as a significant fraction of nitrogen atoms were already protonated, reducing the availability of free amines necessary for endosomal disruption. An appropriate chemical modification to enhance siRNA release from the endosomes is therefore essential for advancing the development of GO-based platforms as versatile and efficient nanocarriers in gene therapy applications. No potential conflict of interest relevant to this article was reported.

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

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

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

Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 64 4 2024 Computed tomography findings of idiopathic multicentric Castleman disease subtypes 292 296 EN Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Noriko Iwaki Department of Hematology, National Cancer Center Hospital Katsuhide Kojima Department of Radiology, Okayama University Hospital Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Fumio Otsuka Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinobu Maeda Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University This study retrospectively evaluated the computed tomography (CT) findings of idiopathic multicentric Castleman disease (iMCD) at a single center and compared the CT findings of iMCD-TAFRO with those of iMCD-non-TAFRO. CT images obtained within 30 days before diagnostic confirmation were reviewed for 20 patients with iMCD (8 men and 12 women, mean age 52.8 } 12.3 years, range 25–74 years). Twelve patients were diagnosed with iMCD-TAFRO, five with iMCD-idiopathic plasmacytic lymphadenopathy, and three with iMCD-not otherwise specified. CT images revealed anasarca and lymphadenopathy in all 20 patients. The iMCD-TAFRO group showed significantly higher frequencies of ascites (100% vs. 37.5%, P = 0.004), gallbladder wall edema (75.0% vs. 12.5%, P = 0.020), periportal collar (91.7% vs. 25.0%, P = 0.004), and anterior mediastinal lesions (non-mass-forming infiltrative lesions) (66.7% vs. 12.5%, P = 0.028). Para-aortic edema tended to be more frequent in patients with the iMCD-TAFRO group (83.3% vs. 37.5%, P = 0.062), while the absence of anterior mediastinal lesions tended to be more frequent in the iMCD-non-TAFRO group (16.7% vs. 62.5%, P = 0.062). These CT findings may have clinical implications for improving the accuracy and speed of iMCD diagnosis and differentiating iMCD-TAFRO from other subtypes. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0032-3896 2025 The stress‒strain behavior of poly(methyl acrylate) microparticle-based polymers determined via optical microscopy EN Yuichiro Nishizawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuto Kawamura raduate School of Textile Science & Technology, Shinshu University Yuma Sasaki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Daisuke Suzuki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The structural integrity of microparticle-based films is maintained through interpenetration of the superficial polymer chains of the microparticles that physically crosslink neighboring microparticles. This structural feature is fundamentally different from those of conventional polymers prepared by solvent casting or bulk polymerization. To understand the mechanical properties of such microparticle-based films, it is necessary to investigate the behavior of their constituent particles. However, methods are still being developed to evaluate microscale structural changes in microparticle-based films during the stretching process leading to film fracture. In this study, we propose a method that combines a stretching stage with optical microscopy to investigate the changes in particle morphology and its positional relationship with surrounding particles during uniaxial tensile tests on microparticle-based films. In a film consisting of cross-linked poly(methyl acrylate) microparticles, the deformation of the particles deviated from affine deformation due to the cross-linked structure. However, the deformation of a group of several (local) particles was confirmed to be location-dependent and larger than that of each particle forming the film. The method established here can be used to contribute to the design of tough microparticle-based films. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0360-3199 140 2025 Advances in filler-crosslinked membranes for hydrogen fuel cells in sustainable energy generation 745 776 EN Aminul Islam Department of Petroleum and Mining Engineering, Jashore University of Science and Technology Mamun Shahriar Department of Petroleum and Mining Engineering, Jashore University of Science and Technology Md. Tarekul Islam Department of Leather Engineering, Faculty of Mechanical Engineering, Khulna University of Engineering and Technology Siow Hwa Teo Industrial Chemistry Program, Faculty of Science and Natural Resources, Universiti Malaysia Sabah M. Azizur R. Khan Department of Chemistry, Jashore University of Science and Technology Yun Hin Taufiq-Yap Catalysis Science and Technology Research Centre, Faculty of Science, Universiti Putra Malaysia Suman C. Mohanta Department of Chemistry, Jashore University of Science and Technology Ariyan Islam Rehan Department of Chemistry, School of Science, The University of Tokyo Adiba Islam Rasee Department of Chemistry, Graduate School of Science, Osaka University Khadiza Tul Kubra Department of Chemistry, Graduate School of Science, Osaka University Md. Munjur Hasan Department of Chemistry, Graduate School of Science, Osaka University Md. Shad Salman Institute for Chemical Research, Kyoto University R.M. Waliullah Institute for Chemical Research, Kyoto University Md. Nazmul Hasan Department of Chemistry, School of Science, The University of Tokyo Md. Chanmiya Sheikh Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Tetsuya Uchida Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Mrs Eti Awual Institute for Chemical Research, Kyoto University Mohammed Sohrab Hossain Department of Chemistry, Graduate School of Science, Osaka University Hussein Znad Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University Md. Rabiul Awual Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University Fuel cell membranes can be used in various ways to achieve zero-emission transport and energy systems, which offer a promising way to power production due to their higher efficiency compared to the internal combustion engine and the eco-environment. Perfluoro sulfonic acid membranes used for proton exchange membranes (PEMs) have certain drawbacks, like higher fuel permeability and expense, lower mechanical and chemical durability, and proton conductivity under low humidity and above 80 ‹C temperature. Researchers have drawn their attention to the production of polymer electrolyte membranes with higher proton conductivity, thermal and chemical resilience, maximum power density, lower fuel permeability, and lower expense. For sustainable clean energy generation, a review covering the most useful features of advanced material-associated membranes would be of great benefit to all interested communities. This paper endeavors to explore several types of novel inorganic fillers and crosslinking agents, which have been incorporated into membrane matrices to design the desired properties for an advanced fuel cell system. Membrane parameters such as proton conductivity, the ability of H2 transport, and the stability of the membrane are described. Research directions for developing fuel cell membranes are addressed based on several challenges suggested. The technological advancement of nanostructured materials for fuel cell applications is believed to significantly promote the future clean energy generation technology in practice. No potential conflict of interest relevant to this article was reported.

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

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

Korean Association for the Study of Intestinal Diseases Acta Medica Okayama 1598-9100 2025 Health-related quality of life, work productivity, and persisting challenges in treated ulcerative colitis patients: a Japanese National Health and Wellness Survey EN Sakiko Hiraoka Department of Gastroenterology, Okayama University Zhezhou Huang Cerner Enviza Fei Qin Cerner Enviza Fatima Megala Nathan Arokianathan Oracle Life Sciences Kiran Davé Bristol Myers Squibb Shweta Shah Bristol Myers Squibb Hyunchung Kim Bristol Myers Squibb Background/Aims Despite available treatments for ulcerative colitis (UC), unmet needs persist among patients in Japan. This study explored the health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), indirect cost, and unmet needs among treated UC patients in Japan.<br> Methods This cross-sectional, observational study utilized data from the online 2017, 2019, and 2021 Japan National Health and Wellness Survey. Respondents were aged ≥ 18 years and had undergone or were on UC treatment (5-aminosalicylic acid, steroids, immunomodulators/immunosuppressants, biologics/Janus kinase inhibitors [JAKi]). Demographic, general health, and clinical characteristics, medication adherence, HRQoL, WPAI, and indirect cost were collected and analyzed.<br> Results Among 293 treated UC patients, 83.6% were non-biologic/JAKi users, 29.0% had UC ≥ 15 years, 34.8% had moderate-to-severe disease severity, 55.3% experienced ≥ 1 persisting UC symptom, and 91.5% reported UC as bothersome to an extent. Patients reported EuroQoL visual analog scale score of 68.1 and ≥ 35% reported anxiety and depression. Mean work productivity loss was 29.3%, resulting in an annual mean indirect loss of 1.1 million JPY (45.3 thousand USD) per person. Higher WPAI (impairment) was associated with being male, moderate-to-severe disease severity, and low treatment adherence (P<0.05). Biologics/JAKi users had higher work impairment, and IM/IS users had higher activity impairment than 5-aminosalicylic acid users (P<0.05).<br> Conclusions Despite treatment, Japanese UC patients experienced high disease burden and persistent disease-related challenges. Overall HRQoL were lower than the mean healthy population and work productivity impairment led to high indirect costs. The findings suggest the importance of new interventions for optimizing UC outcomes. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 1572-1000 54 2025 Near-infrared photoimmunotherapy for recurrent cancer at the base of the tongue 104719 EN Takuma Makino Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Asami Nishikori Department of Hematopathology, Okayama University Graduate School of Health Sciences Yasuharu Sato Department of Hematopathology, Okayama University Graduate School of Health Sciences Yuto Naoi Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junya Matsumoto Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Fujimoto Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Near-infrared photoimmunotherapy (NIR-PIT) is a novel therapeutic approach that targets epidermal growth factor receptor (EGFR). In NIR-PIT, administration of cetuximab sarotalocan sodium is followed by laser irradiation of the affected area, which theoretically should induce tumor cell death. However, residual tumors are occasionally observed. This study investigated factors that influence the therapeutic efficacy of NIR-PIT in cases of recurrence of cancer at the base of the tongue. Six patients undergoing 11 treatment cycles were analyzed, focusing on the puncture interval of cylindrical diffusers and the expression of EGFR in tumors. The results demonstrated that a puncture interval of ≤12 mm significantly enhanced therapeutic efficacy, with one case achieving complete response. EGFR expression was positive in all cases and expression score showed no significant change between before and after treatment. These findings suggest that puncture interval plays a critical role in therapeutic outcomes, whereas EGFR expression may not directly influence treatment efficacy. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1436-3771 29 8 2025 Clinical and microbiological effects of a propolis toothpaste in patients with periodontitis under supportive periodontal therapy: a randomized double-blind clinical trial 379 EN Kazu Takeuchi-Hatanaka Department of Periodontics and Endodontics, Okayama University Hospital Masahiro Ito Department of Periodontics and Endodontics, Okayama University Hospital Yoshihiro Hayashi Department of Periodontics and Endodontics, Okayama University Hospital Hiroe Maruyama Department of Periodontics and Endodontics, Okayama University Hospital Hiroyuki Kono Department of Periodontics and Endodontics, Okayama University Hospital Yuki Shinoda-Ito Department of Pathophysiology–Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Omori Department of Pathophysiology–Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Takashiba Department of Pathophysiology–Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives Propolis possesses antibacterial, anti-inflammatory, and antioxidant properties. While its application in oral care has garnered significant attention, evidence supporting its effectiveness against periodontal bacteria is limited. This study used a randomized double-blind protocol to assess the safety and efficacy of toothpaste containing propolis compared to a placebo in patients undergoing supportive periodontal therapy (SPT).<br> Materials and methods Thirty-two participants in SPT were randomized into two groups: toothpaste containing 2.5% ethanol-extracted propolis (EEP) and a placebo without EEP. Participants brushed twice daily for four weeks, and clinical parameters, bacterial counts, and salivary characteristics were assessed before and after the intervention.<br> Results The propolis group showed a significant reduction in periodontal pocket depth (P = 0.006), with a mean depth of 3.80 mm compared to 4.35 mm in the placebo group. Bleeding on probing was significantly reduced in both groups (P = 0.032 in the propolis group and 0.0498 in the placebo group), but did not differ between groups. Total bacterial and Porphyromonas gingivalis (P. gingivalis) counts did not differ significantly between the groups; however, the number of patients with decreased P. gingivalis was slightly larger than those in the placebo group (not significant). Additionally, saliva acidity decreased significantly in the propolis group (P = 0.041), suggesting a shift toward a less pathogenic oral environment. No adverse events were observed.<br> Conclusion These findings suggest that propolis may contribute to stabilizing periodontal disease during supportive periodontal therapy by modulating salivary acidity.<br> Clinical relevance Periodontal pocket depth and the rate of bleeding on probing are reduced, along with decreased saliva acidity. Meanwhile, the levels of P. gingivalis in the periodontal pockets remain low. Propolis-dentifrice may help alleviate gingival inflammation during SPT.<br> Clinical trial registration Registered in the University Hospital Medical Information Network Clinical Trial Registry (ID: UMIN000029554). No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Observation of the Radiative Decay from the Isomeric State of Thorium-229 EN Koichi OKAI Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Effect of Radon Inhalation on Murine Brain Proteins : Investigation Using Proteomic and Multivariate Analyses EN Shota NAOE Graduate School of Health Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

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

Acta Medica Okayama 2025 ‘g•R»‘’‹Zp‚Ι‚ζ‚ι‘@ˆΫ‹­‰»Œ^lH‹Ψ“χ‚̐»μŽθ–@‚ΜŠm—§‚Ζ•ΟˆΚƒZƒ“ƒVƒ“ƒO‚ΜŽΐŒ» EN WEIHANG TIAN Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Palladium-Catalyzed Decarbonylative Halogenation of Carboxylic Acid Derivatives EN Tian TIAN Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Rates and risk factors of bleeding after gastric endoscopic submucosal dissection with continuous warfarin or 1-day withdrawal of direct oral anticoagulants EN Shoichiro HIRATA 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 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 Partial versus Radical Nephrectomy for Small Renal Cancer: Comparative Propensity Score-Matching Analysis of Cardiovascular Event Risk EN Risa KUBOTA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

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

BMC Acta Medica Okayama 1471-230X 25 1 2025 Efficient diagnosis for endoscopic remission in Crohn's diseases by the combination of three non-invasive markers 364 EN Kensuke Takei Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshihiro Inokuchi Research Center for Intestinal Health Science, Okayama University Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikako Ishiguro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junki Toyosawa Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Aoyama Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoko Igawa Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiko Takeuchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasushi Yamasaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideaki Kinugasa Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Takahara Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Serum C-reactive protein (CRP), leucine-rich alpha-2 glycoprotein (LRG), and fecal calprotectin (Fcal) are non-invasive markers used to assess Crohn's disease (CD) severity. However, the accuracy of these markers alone is often limited, and most previous reports have evaluated the efficacy of each marker individually. We aimed to improve the diagnostic performance of endoscopic remission (ER) of CD by combining these 3 markers.<br> Methods We tested the diagnostic ability of various combinations of these 3 markers for endoscopic severity in 230 consecutive patients with CD from September 2014 to July 2023. The modified Simple Endoscopic Score for Crohn's disease (mSES-CD) was used to determine endoscopic severity.<br> Results Each of the 3 markers was correlated with mSED-CD (LRG: r = 0.69, CRP: r = 0.60, and Fcal: r = 0.67). A combination of 2 of the 3 markers did not increase the diagnostic accuracy of ER. However, by combining all 3 markers, the diagnostic ability for ER was improved in comparison to the diagnostic ability of the 3 individual markers, assuming that ER was obtained if 2 or 3 markers were negative. The sensitivity, specificity, and accuracy were 89%, 83%, and 86%, respectively. Additionally, we established a 2-step method using Fcal values after evaluating the 2 serum markers. This method was most useful for reducing both the patient burden and costs.<br> Conclusions The newly established 2-step method allowed for a higher accuracy in the non-invasive diagnosis of ER when the 3 markers were combined. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 0910-8327 2025 Outcomes of ultra-high-pressure balloon angioplasty for congenital heart disease in single-center experience EN Maiko Kondo Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kurita Department of Pediatrics, Okayama University Hospital Yosuke Fukushima Department of Pediatrics, Okayama University Hospital Yusuke Shigemitsu Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenta Hirai Department of Pediatrics, Okayama University Hospital Yuya Kawamoto Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mayuko Hara Department of Pediatrics, Okayama University Hospital Tomoyuki Kanazawa Department of Pediatric Anesthesiology, Okayama University Hospital Tatsuo Iwasaki Department of Pediatric Anesthesiology, Okayama University Hospital Yasuhiro Kotani Department of Cardiovascular Surgery, Okayama University Hospital Shingo Kasahara Department of Cardiovascular Surgery, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Hospital Kenji Baba Department of Pediatrics, Okayama University Hospital Angioplasty using ultra-high-pressure (UHP) balloons may successfully treat stenotic lesions refractory to high-pressure dilation. The use of UHP balloons in patients with congenital heart disease is mostly for dilation of the pulmonary artery, and there have been few reports on the effectiveness and safety of balloons for other sites. We retrospectively evaluated the efficacy and safety of the ultra-high-pressure balloon angioplasty (UHP-BA) for stenotic lesions in patients with congenital heart disease between January 2020 and December 2022 at Okayama University Hospital. A total of 78 UHP-BAs were performed in 44 patients, with a median age of 6.6 years and a median weight of 17.6 kg. The balloon types used in the UHP-BAs were Yoroi® and Conquest®. UHP-BA performed 39 procedures for the pulmonary artery (PA), 24 for fenestration, 8 for SVC, 4 for shunt, and three for others. The lesion-specific acute procedural success rates for PA, Fontan fenestration, SVC, and shunt were 77%, 75%, 88%, and 75%, respectively. A complication of UHP-BA occurred in 3.8% (3/78). Two of the three patients had pulmonary hemorrhage, and the remaining patients had pulmonary artery embolization due to the migration of a thrombus. There were no fatal complications. Balloon dilation with UHP balloons was safe and effective not only for pulmonary artery stenotic lesions but also for SVC, Fontan fenestration, shunt, and other dilation sites in patients with congenital heart disease. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 0019-9567 2025 Xenopus laevis as an infection model for human pathogenic bacteria EN Ayano Kuriu Division of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kazuya Ishikawa Division of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohsuke Tsuchiya Division of Immunology and Molecular Biology, Cancer Research Institute, Kanazawa University Kazuyuki Furuta Division of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Chikara Kaito Division of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Animal infection models are essential for understanding bacterial pathogenicity and corresponding host immune responses. In this study, we investigated whether juvenile Xenopus laevis could be used as an infection model for human pathogenic bacteria. Xenopus frogs succumbed to intraperitoneal injection containing the human pathogenic bacteria Staphylococcus aureus, Pseudomonas aeruginosa, and Listeria monocytogenes. In contrast, non-pathogenic bacteria Bacillus subtilis and Escherichia coli did not induce mortality in Xenopus frogs. The administration of appropriate antibiotics suppressed mortality caused by S. aureus and P. aeruginosa. Strains lacking the agr locus, cvfA (rny) gene, or hemolysin genes in S. aureus, LIPI-1-deleted mutant of L. monocytogenes, which attenuate virulence within mammals, exhibited reduced virulence in Xenopus frogs compared with their respective wild-type counterparts. Bacterial distribution analysis revealed that S. aureus persisted in the blood, liver, heart, and muscles of Xenopus frogs until death. These results suggested that intraperitoneal injection of human pathogenic bacteria induces sepsis-like symptoms in Xenopus frogs, supporting their use as a valuable animal model for evaluating antimicrobial efficacy and identifying virulence genes in various human pathogenic bacteria. No potential conflict of interest relevant to this article was reported.

Optica Publishing Group Acta Medica Okayama 1094-4087 33 8 2025 Demonstration of enhanced Raman scattering in high-Q silicon nanocavities operating below the silicon band-gap wavelength 18515 18529 EN Yu Shimomura Department of Physics and Electronics, Osaka Metropolitan University Takashi Asano Department of Electronic Science and Engineering, Kyoto University Ayumi Ishihara Department of Physics and Electronics, Osaka Metropolitan University Susumu Noda Department of Electronic Science and Engineering, Kyoto University Yasushi Takahashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University We experimentally determined the quality factor (Q) and the intensity of the Raman scattered light for different silicon photonic-crystal nanocavities operating at wavelengths shorter than the silicon band-gap wavelength. Despite the relatively large absorption of silicon in this wavelength region, we observed Q values greater than 10,000 for cavities with a resonance wavelength of 1.05 mu m, and Q values greater than 30,000 for cavities with a resonance wavelength of 1.10 mu m. Additionally, we measured the Raman scattering spectra of cavities with resonance wavelengths of 1.10 mu m and 1.21 mu m. On average, the generation efficiency of the Raman scattered light in a 1.10-mu m nanocavity is 6.5 times higher than that in a 1.21-mu m nanocavity. These findings suggest that silicon nanocavities operating below the silicon band-gap wavelength could be useful in the development of silicon-based light sources. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0168-0102 214 2025 The Medaka approach to evolutionary social neuroscience 32 41 EN Satoshi Ansai Ushimado Marine Institute, Okayama University Towako Hiraki-Kajiyama Graduate School of Life Sciences, Tohoku University Ryutaro Ueda Graduate School of Life Sciences, Tohoku University Takahide Seki Graduate School of Life Sciences, Tohoku University Saori Yokoi School of Pharmaceutical Sciences, Hokkaido University Takafumi Katsumura School of Medicine, Kitasato University Hideaki Takeuchi Graduate School of Life Sciences, Tohoku University Previously, the integration of comparative biological and neuroscientific approaches has led to significant advancements in social neuroscience. This review highlights the potential and future directions of evolutionary social neuroscience research utilizing medaka fishes (the family Adrianichthyidae) including Japanese medaka (Oryzias latipes). We focus on medaka social cognitive capabilities and mate choice behavior, particularly emphasizing mate preference using visual cues. Medaka fishes are also advantageous due to their abundant genetic resources, extensive genomic information, and the relative ease of laboratory breeding and genetic manipulation. Here we present some research examples of both the conventional neuroscience approach and evolutionary approach involving medaka fishes and other species. We also discuss the prospects of uncovering the molecular and cellular mechanisms underlying the diversity of visual mate preference among species. Especially, we introduce that the single-cell transcriptome technology, particularly in conjunction with 'Adaptive Circuitry Census', is an innovative tool that bridges comparative biological methods and neuroscientific approaches. Evolutionary social neuroscience research using medaka has the potential to unveil fundamental principles in neuroscience and elucidate the mechanisms responsible for generating diversity in mating strategies. No potential conflict of interest relevant to this article was reported.

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

Frontiers Media Acta Medica Okayama 1664-3224 16 2025 PARylation-mediated post-transcriptional modifications in cancer immunity and immunotherapy 1537615 EN Kazuya Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinori Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Poly-ADP-ribosylation (PARylation) is a post-translational modification in which ADP-ribose is added to substrate proteins. PARylation is mediated by a superfamily of ADP-ribosyl transferases known as PARPs and influences a wide range of cellular functions, including genome integrity maintenance, and the regulation of proliferation and differentiation. We and others have recently reported that PARylation of SH3 domain-binding protein 2 (3BP2) plays a role in bone metabolism, immune system regulation, and cytokine production. Additionally, PARylation has recently gained attention as a target for cancer treatment. In this review, we provide an overview of PARylation, its involvement in several signaling pathways related to cancer immunity, and the potential of combination therapies with PARP inhibitors and immune checkpoint inhibitors. No potential conflict of interest relevant to this article was reported.

American Association for Cancer Research (AACR) Acta Medica Okayama 0008-5472 85 6 2025 Myeloid Cells Induce Infiltration and Activation of B Cells and CD4+ T Follicular Helper Cells to Sensitize Brain Metastases to Combination Immunotherapy 1082 1096 EN Toshifumi Ninomiya Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoya Kemmotsu Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumiaki Mukohara Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaki Magari Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ai Miyamoto Medical Protein Engineering, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Youki Ueda Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takamasa Ishino Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Joji Nagasaki Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Fujiwara Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hidetaka Yamamoto Department of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidetoshi Hayashi Department of Medical Oncology, Kindai University Faculty of Medicine Kota Tachibana Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Joji Ishida Department of Neurological Surgery, 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 Shota Tanaka Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinichi Toyooka Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University Isamu Okamoto Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University Yosuke Togashi Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Brain metastasis is a poor prognostic factor in patients with cancer. Despite showing efficacy in many extracranial tumors, immunotherapy with anti–PD-1 mAb or anti–CTLA4 mAb seems to be less effective against intracranial tumors. Promisingly, recent clinical studies have reported that combination therapy with anti–PD-1 and anti–CTLA4 mAbs has a potent antitumor effect on brain metastasis, highlighting the need to elucidate the detailed mechanisms controlling the intracranial tumor microenvironment (TME) to develop effective immunotherapeutic strategies. In this study, we analyzed the tumor-infiltrating lymphocytes in murine models of brain metastasis that responded to anti–CTLA4 and anti–PD-1 mAbs. Activated CD4+ T follicular helper (TFH) cells with high CTLA4 expression characteristically infiltrated the intracranial TME, which were activated by combination anti–CTLA4 and anti–PD-1 treatment. The loss of TFH cells suppressed the additive effect of CTLA4 blockade on anti–PD-1 mAb. B-cell–activating factor belonging to the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) produced by abundant myeloid cells, particularly CD80hiCD206lo proinflammatory M1-like macrophages, in the intracranial TME induced B-cell and TFH-cell infiltration and activation. Furthermore, the intracranial TME of patients with non–small cell lung cancer featured TFH- and B-cell infiltration as tertiary lymphoid structures. Together, these findings provide insights into the immune cell cross-talk in the intracranial TME that facilitates an additive antitumor effect of CTLA4 blockade with anti–PD-1 treatment, supporting the potential of a combination immunotherapeutic strategy for brain metastases.<br> Significance: B-cell and CD4+ T follicular helper cell activation via BAFF/APRIL from abundant myeloid cells in the intracranial tumor microenvironment enables a combinatorial effect of CTLA4 and PD-1 blockade in brain metastases. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0006-291X 752 2025 Discovery of myeloid zinc finger (MZF) 1 nuclear bodies 151481 EN Takanori Eguchi Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Stuart K. Calderwood Division of Molecular and Cellular Biology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School Myeloid zinc finger 1 (MZF1) is a multifaceted transcription factor that can act either as a transcriptional activator or a gene repressor. We examined its production of nuclear bodies (NBs) and subcellular localization. Proteomic and protein–protein interaction analysis were used to identify its cofactors and interactions. These revealed the presence of MZF1-NBs (intranuclear oligomers containing MZF1). MZF-NBs are similar to some other nuclear bodies, notably promyelocytic leukemia (PML) -NBs in terms of size and morphology. However the two structures appear to be different. MZF-NBs and PML-NBs were found to associate in the nucleus. Both MZF1 and PML are SUMO1-SUMOylated in PC-3 cells. Sumoylated MZF1 can interact with proteins containing SUMO-interaction motifs (SIM) through SUMO-SIM interaction. Interactome analysis revealed that its NBs participate in the stress response (TPR and UBAP2L), protein folding (CALR and ANKRD40), transcription, post-translational modification (TRIM33, ACOT7, CAMK2D, and CAMK2G), and RNA binding (ALURBP and CPSF5). No potential conflict of interest relevant to this article was reported.

‰ͺŽR‘εŠwŽ‘ŒΉA•¨‰ΘŠwŒ€‹†Š Acta Medica Okayama 2186-4918 32 2025 ‰ͺŽR‘εŠwŽ‘ŒΉA•¨‰ΘŠwŒ€‹†Š•ρ 1 60 EN Institute of Plant Science and Resources, Okayama University No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0941-4355 33 4 2025 Characteristics of oral mucositis in patients undergoing haploidentical stem cell transplantation with posttransplant cyclophosphamide: marked difference between busulfan and melphalan regimens 252 EN Saki Ogura Division of Dental Hygienist, Okayama University Hospital Yoshihiko Soga Division of Hospital Dentistry, Okayama University Hospital Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Rumi Miura Division of Dental Hygienist, Okayama University Hospital Ken-ichi Matsuoka Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuo Kuboki Division of Dental Hygienist, Okayama University Hospital Purpose This study was performed to examine the effects of conditioning regimens on oral mucositis in haploidentical (haplo) donor hematopoietic stem cell transplantation (HSCT) with posttransplant cyclophosphamide (PTCy).<br> Methods Thirty consecutive patients (male, 23; female, 7; 18–68 years, median, 59 years) undergoing haplo-HSCT with PTCy using one of three conditioning regimens\reduced intensity conditioning (RIC)-melphalan (Mel); RIC-Busulfan (Bu); and myeloablative conditioning (MAC)-Bu\were enrolled in this study. Data on the WHO grade of oral mucositis (day | 7 to + 20) were collected retrospectively. The incidences of ulcerative and severe mucositis (Grade 2–4 and Grade 3–4, respectively) were compared between the three groups.<br> Results Ulcerative mucositis occurred in 0% (0/10) of patients in the RIC-Mel group, 57.1% (4/7) in the RIC-Bu group, and 100% (13/13) in the MAC-Bu group. The differences between the RIC-Mel and RIC-Bu groups and between the RIC-Bu and MAC-Bu groups were significant (all P < 0.05). Severe mucositis occurred in 57.1% (4/7) of patients in the RIC-Bu group and 100% (13/13) of patients in the MAC-Bu group, and the difference was significant (P < 0.05). The rates of ulcerative mucositis (≥ grade 2) and of severe mucositis (≥ grade 3) were significantly higher in the MAC-Bu group than the RIC-Bu group on days 10, 13, 15, and 16 and on days 10, 14, 15, and 16, respectively (all P < 0.05).<br> Conclusion The risk of oral mucositis in patients undergoing haplo-HSCT with PTCy is highest with the MAC-Bu conditioning regimen, followed by RIC-Bu, and lowest with RIC-Mel. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 15 1 2025 Changes of leucine-rich alpha 2 glycoprotein could be a marker of changes of endoscopic and histologic activity of ulcerative colitis 5248 EN Yuki Aoyama Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sakiko Hiraoka Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eriko Yasutomi Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshihiro Inokuchi Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takehiro Tanaka Department of Pathology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kensuke Takei Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shoko Igawa Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiko Takeuchi Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiro Takahara Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junki Toyosawa Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasushi Yamasaki Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hideaki Kinugasa Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Kato Department of Gastroenterology, Graduate School of Medicine, Chiba University Hiroyuki Okada Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Leucine-rich alpha 2 glycoprotein (LRG) is one of the serum biomarkers for disease activity of ulcerative colitis (UC). We focused on the correlation between the changes of LRG and the changes of endoscopic and histologic activity of UC, in comparison to the changes of fecal calprotectin (Fcal), fecal immunochemical test (FIT), and C-reactive protein (CRP). Seventy-nine patients with two or more colonoscopies were enrolled, and 123 paired colonoscopies and 121 paired biopsies were examined. With regard to the change of endoscopic/histologic activity between the preceding and subsequent colonoscopy, there was improvement (n = 29/45), unchanging (n = 63/36), and worsening (n = 31/40). The correlations between the changes of marker levels and endoscopic/histologic activity were Fcal; r = 0.50/0.39 and FIT; r = 0.41/0.40, LRG; r = 0.42/0.40 and CRP; r = 0.22/0.17. Furthermore, when the correlation between the changes of LRG levels and the changes of endoscopic/histological activity was compared with those of other markers, the correlation of LRG tended to be superior to those of CRP (CRP vs. LRG; p = 0.08/0.01). LRG is equivalent to fecal markers and superior to CRP, when inferring changes in disease activity of UC based on changes in its level. 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 gTAFROh 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.

Wiley Acta Medica Okayama 0309-0167 2025 Kikuchi]Fujimoto disease: investigating comprehensive clinicopathological features and risk factors for recurrence EN Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Chikako Sakao Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yuka Kurokawa Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yoshito Nishimura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Hidetaka Yamamoto Department of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Aims: Kikuchi-Fujimoto disease (KFD) is a rare disease that typically manifests with fever and cervical lymphadenopathy. Little is known about the risk factors associated with recurrence and their correlation with clinicopathologic features.<br> Methods and Results: We analysed 112 patients with KFD, predominantly female (61/112, 54.5%), with an average age of 29.4 years. The incidence was higher in males up to the age of 20 and higher in females from their 30s onwards. Of the 70 patients with follow-up data, 23% experienced recurrence. Recurrence was associated with lower C4 levels (P = 0.038) and higher antinuclear antibody (ANA) rates (P = 0.007) compared to transient disease. The mean duration of symptoms was 71.5 days. Lymph node histology in 98 cases (excluding 14 needle biopsy specimens) was classified into three patterns: proliferative (n = 75, 77%), necrotizing (n = 22, 22%), and xanthomatous (n = 1, 1%). The necrotizing pattern associated with significantly enlarged lymph nodes (P = 0.047) and a longer symptom duration (P = 0.009) than the proliferating pattern. The number of CD4-positive lymphocytes was significantly lower in the necrotizing type than in the proliferative type (P < 0.001).<br> Conclusion: These results indicated that low C4 levels and positive ANA were associated with KFD recurrence. Although the aetiology of KFD remains elusive, given that some cases develop autoimmune disease, the results suggest that patients with recurrent KFD represent an intermediate status between those with transient KFD and those with overt autoimmune disease. The comprehensive clinicopathological findings of this study may be useful for elucidating its pathogenesis and predicting the clinical course. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0950-5423 60 1 2025 The effects of soybeans and its derivatives on oral diseases: a narrative review vvae044 EN Kuang Canyan Department of Pathophysiology\Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Zulema Rosalia Arias Department of Pathophysiology\Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Omori Department of Pathophysiology\Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Yamamoto The Center for Graduate Medical Education (Dental Division), Okayama University Hospital Yuki Shinoda-Ito Department of Pathophysiology\Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shogo Takashiba Department of Pathophysiology\Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soybean is a widely utilized protein source that originated in China and has been associated with preventing and treating various diseases. Soy protein has been found to inhibit fat accumulation effectively, and soybeans contain isoflavones, saponins, phytic acid, and other substances with preventive and therapeutic effects on heart disease, cancer, and diabetes. Furthermore, processed soybean products, such as Avocado-Soybean unsaponifiable, Tempeh, and Bowman-Birk inhibitor, have demonstrated health benefits. These products have been shown to have antibacterial, antioxidant, and anticancer effects in oral diseases. Numerous experiments have provided evidence of the antibacterial, antioxidant, and anticancer effects of polyunsaturated fatty acids, isoflavones, and soybean polypeptides. This comprehensive review assesses the relationship and mechanism of soybeans and their derivatives on oral diseases, providing valuable insights into their prevention and treatment. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1359-7345 61 24 2025 Nano/microparticle-based tough and recyclable polymers toward a sustainable society 4606 4620 EN Yuma Sasaki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuichiro Nishizawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takuma Kureha Department of Frontier Materials Chemistry, Graduate School of Science and Technology, Hirosaki University Daisuke Suzuki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University By virtue of their unique properties, polymer nano/microparticles constitute important building blocks for the construction of functional nanomaterials. Although intense research efforts in this field have laid the foundation for the applications of polymer nano/microparticle-based latex films, cutting-edge innovations in the recycling of polymer materials are still required for the realization of a sustainable society. This feature article reviews our recent attempts to develop the applications of polymer nano/microparticles in the context of a circular society on the basis of the precise synthesis of single nano/microparticles and multiscale structural analysis. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1029-8428 43 1 2025 Differentially Expressed Nedd4-binding Protein Ndfip1 Protects Neurons Against Methamphetamine-induced Neurotoxicity 4 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 Jean Lud Cadet Molecular Neuropsychiatry Section, Intramural Research Program, NIH/ NIDA To identify factors involved in methamphetamine (METH) neurotoxicity, we comprehensively searched for genes which were differentially expressed in mouse striatum after METH administration using differential display (DD) reverse transcription-PCR method and sequent single-strand conformation polymorphism analysis, and found two DD cDNA fragments later identified as mRNA of Nedd4 (neural precursor cell expressed developmentally downregulated 4) WW domain-binding protein 5 (N4WBP5), later named Nedd4 family-interacting protein 1 (Ndfip1). It is an adaptor protein for the binding between Nedd4 of ubiquitin ligase (E3) and target substrate protein for ubiquitination. Northern blot analysis confirmed drastic increases in Ndfip1 mRNA in the striatum after METH injections, and in situ hybridization histochemistry showed that the mRNA expression was increased in the hippocampus and cerebellum at 2 h-2 days, in the cerebral cortex and striatum at 18 h-2 days after single METH administration. The knockdown of Ndfip1 expression with Ndfip1 siRNA significantly aggravated METH-induced neurotoxicity in the cultured monoaminergic neuronal cells. These results suggest that drastic increases in Ndfip1 mRNA is compensatory reaction to protect neurons against METH-induced neurotoxicity. No potential conflict of interest relevant to this article was reported.

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

Elsevier Acta Medica Okayama 0006-4971 145 8 2025 Oral Inflammation and Microbiome Dysbiosis Exacerbate Chronic Graft-versus-host Disease 881 896 EN Yui Kambara Department of Hematology, Oncology and Respiratory Medicine, Okayama University Medical School Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Akira Yamamoto Department of Hematology and Oncology, Okayama University Hospital Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Shuma Tsuji Department of Microbiology and Genetics, Okayama University Graduate School of Health Sciences Mari Kunihiro Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Oyama Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiki Terao Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayame Sato Division of Hospital Dentistry, Okayama University Hospital Takehiro Tanaka Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daniel Peltier Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Department of Pediatrics, Herman B Wells Center for Pediatric Research, Simon Cancer Center, Indiana University School of Medicine Keisuke Seike Department of Hematology and Oncology, Okayama University Hospital Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Keiko Fujii Department of Clinical Laboratory, Okayama University Hospital Nobuharu Fujii Division of Blood Transfusion, Okayama University Hospital Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Hospital Yoshihiko Soga Division of Hospital Dentistry, Okayama University Hospital Pavan Reddy Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine Maeda Yoshinobu Department of Hematology and Oncology, Okayama University Hospital The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes both before and after transplantation activated antigen-presenting cells, thereby promoting the expansion of donor-derived inflammatory T cells. Based on these results, we hypothesize that pathogenic bacteria increase in the oral cavity might not only exacerbate local inflammation but also enhance systemic inflammation throughout the HCT course. Additionally, these bacteria translocated to the gut and formed ectopic colonies, further amplifying systemic inflammation. Furthermore, interventions targeting the oral microbiome mitigated murine cGVHD. Collectively, our findings highlight the importance of oral dysbiosis in cGVHD and suggest that modulation of the oral microbiome during transplantation may be an effective approach for preventing or treating cGVHD. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6694 16 23 2024 Frequency and Significance of Body Weight Loss During Immunochemotherapy in Patients with Advanced Non-Small Cell Lung Cancer 4089 EN Masataka Taoka Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Toshihide Yokoyama Department of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital Koji Inoue Department of Respiratory Medicine, Ehime Prefectural Central Hospital Tomoki Tamura Department of Respiratory Medicine, NHO Iwakuni Clinical Center Akiko Sato Department of Internal Medicine, National Hospital Organization Okayama Medical Center Naohiro Oda Department of Respiratory Medicine, Fukuyama City Hospital Hirohisa Kano Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Kayo Nakamura Department of Respiratory Medicine, Japanese Red Cross Himeji Hospital Haruyuki Kawai Department of Internal Medicine, Okayama Saiseikai General Hospital Masaaki Inoue Department of Chest Surgery, Shimonoseki City Hospital Nobuaki Ochi Department of General Internal Medicine 4 , Kawasaki Medical School Nobukazu Fujimoto Department of Respiratory Medicine, Okayama Rosai Hospital Hirohisa Ichikawa Department of Respiratory Medicine, KKR Takamatsu Hospital Chihiro Ando Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Isao Oze Division of Cancer Information and Control, Aichi Cancer Center Research Institute Katsuyuki Kiura Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Background: Limited data are available on the frequency and significance of body weight loss during cancer therapy. This study investigated the frequency of patients who experienced body weight loss during immune checkpoint inhibitor (ICI) plus chemotherapy for advanced non-small cell lung cancer (NSCLC) and the impact of weight loss on treatment outcomes. Methods: Using the clinical data of 370 patients with NSCLC who received a combination of ICI and chemotherapy at 13 institutions, this study investigated the frequency of body weight loss > 5% during treatment and determined the impact of body weight loss on patient outcomes. Results: Of the 370 included patients, 141 (38.1%) lost more than 5% of their body weight during ICI plus chemotherapy (WL group). The 2-month landmark analysis showed that patients who experienced body weight loss of >5% during treatment had worse overall survival (OS) and progression-free survival (PFS) than those who did not (OS 14.0 and 31.1 months in the WL non-WL groups, respectively, p < 0.001; PFS 6.8 and 10.9 months in the WL non-WL groups, respectively, p = 0.002). Furthermore, a negative impact of body weight loss on survival was observed even in those who had obesity (body mass index [BMI] >= 25.0) at the start of therapy (OS 12.8 and 25.4 months in the WL non-WL groups, respectively, p < 0.001; PFS 5.7 and 10.7 months in the WL non-WL groups, respectively, p = 0.038). Conclusions: In conclusion, weight loss of >5% during ICI plus chemotherapy negatively influenced patient outcomes. Further and broader studies should investigate the role of nutritional status, specifically weight change and nutritional support, in responsiveness to ICI plus chemotherapy. No potential conflict of interest relevant to this article was reported.

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

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

Acta Medica Okayama 2024 Copy Number Analysis of 9p24.1 in Classic Hodgkin Lymphoma Arising in Immune Deficiency/Dysregulation EN Kumiko OHSAWA Graduate School of Health Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Development of Peptide Nanomicelle for siRNA Delivery into Cancer Cells EN TAUFIK FATWA NUR HAKIM Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Recognition Methodology of Deformable String State Using Visual Information Processing for Robotic Manipulation EN JUNXIANG WANG Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Heat Exposure Following the Rainy Season Is Associated With an Increased Risk of Cardiovascular Emergency Among the Elderly in Japan EN Ryohei FUJIMOTO 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 Depiction rate of feeding arteries of renal cell carcinoma on four‑dimensional computed tomography angiography EN Kazuaki MUNETOMO Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1471-2482 24 1 2024 The required experience of open pancreaticoduodenectomy before becoming a specialist in hepatobiliary and pancreatic surgeons: a multicenter, cohort study of 334 open pancreaticoduodenectomies 366 EN Tomokazu Fuji Department of Gastroenterological Surgery Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masayoshi Hioki Department of Surgery, Fukuyama City Hospital Ryuichi Yoshida Department of surgery, Hiroshima Citizens Hiroshima Citizens Hospital Yoshikatsu Endo Department of Surgery, Japanese Red Cross Society Himeji Hospital Kazuya Yasui Department of Gastroenterological Surgery Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daisuke Nobuoka Department of Gastroenterological Surgery, Kagawa Prefectural Central Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background Open pancreaticoduodenectomy (OPD) is an essential surgical procedure for expert hepato-biliary-pancreatic (HBP) surgeons. However, there is no standard for how many surgeries must be performed by a surgeon in training before they are considered to have enough experience to ensure surgical safety. <br> Methods Cumulative Sum (CUSUM) analysis was performed using the surgical data of OPDs performed during the training period of board-certified expert surgeons of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. <br> Results Fourteen HBP surgeons participated in this study and performed 334 OPDs during their training period. The median (interquartile range) values for operative time, blood loss, and length of hospital stay were 455 (397-519) minutes, 450 (234--716) ml, and 28 (21-38) days, respectively. CUSUM analysis showed inflection points at 20 surgeries performed for operative time. After 20 procedures, operative time was significantly shorter (461 min vs. 425 min, p = 0.021) and blood loss was significantly lower (470 ml vs. 340 ml, p = 0.038). No significant differences between within 20 and after 21 procedures were found in the complication rate (53% vs. 48%, p = 0.424) and rate of in-hospital deaths (1.5% vs.1.4%. p = 0.945). Up to 20 surgeries, PDAC and another malignant tumor had longer operative time than benign/low malignant diseases (486 min vs. 472 min vs. 429 min, p < 0.001), and higher blood loss (500 ml vs. 502 ml vs. 355 ml, p < 0.001). Mortality rate was higher at PDAC cases (5% vs. 0% vs. 0%, p = 0.01). After the 21 procedures, these outcomes were improved and no differences in by primary disease were observed. Multivariable analysis showed that within 20 surgeries were independent risk factors of longer operative time (HR2.6, p = 0.013) and higher blood loss (HR2.0, p = 0.049). <br> Conclusions To stabilize the surgical outcome of OPD for malignant disease, at least 20 surgeries should be performed at a certified institution during surgeon training. Trial registrationClinical trial number: Not applicable. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0085-2538 106 5 2024 A randomized, open-label, clinical trial examined the effects of canagliflozin on albuminuria and eGFR decline using an individual pre-intervention eGFR slope 972 984 EN Satoshi Miyamoto Center for Innovative Clinical Medicine, Okayama University Hospital Hiddo J.L. Heerspink Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen Dick de Zeeuw Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen Kota Sakamoto Center for Innovative Clinical Medicine, Okayama University Hospital Michihiro Yoshida Center for Innovative Clinical Medicine, Okayama University Hospital Masao Toyoda Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine Daisuke Suzuki Suzuki Diadetes Clinic Takashi Hatanaka Department of Diabetes and Endocrinology, National Hospital Organization Fukuyama Medical Center Tohru Nakamura Diabetes Internal Medicine, Sumitomo Besshi Hospital Shinji Kamei Department of Diabetic Medicine, Kurashiki Central Hospital Satoshi Murao Department of Diabetes and Endocrinology, Takamatsu Hospital Kazuyuki Hida Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center Shinichiro Ando Department of Internal Medicine Diabetic Center, Okayama City Hospital Hiroaki Akai Division of Diabetes and Metabolism, Faculty of Medicine, Tohoku Medical and Pharmaceutical University Yasushi Takahashi Department of Diabetes, Ochiai General Hospital Munehiro Kitada Department of Diabetology and Endocrinology, Kanazawa Medical University Hisashi Sugano Department of Diabetes and Endocrinology, Kochi Health Sciences Center Tomokazu Nunoue Nunoue Clinic Akihiko Nakamura Internal Medicine, Osafune Clinic Motofumi Sasaki Department of Diabetes and Endocrinology, Matsue City Hospital Tatsuaki Nakatou Diabetes Center, Okayama Saiseikai General Hospital Kei Fujimoto Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, The Jikei University Kashiwa Hospital Daiji Kawanami Department of Endocrinology and Diabetes, Fukuoka University School of Medicine Takashi Wada Department of Nephrology and Laboratory Medicine, Graduate School of Medical Sciences, Kanazawa University Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Hiromi Kuramoto Center for Innovative Clinical Medicine, Okayama University Hospital Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital Demonstrating drug efficacy in slowing kidney disease progression requires large clinical trials when targeting participants with an early stage of chronic kidney disease (CKD). In this randomized, parallel-group, open-labeled trial (CANPIONE study), we assessed the effect of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin using the individualfs change in estimated glomerular filtration rate (eGFR) slope before (pre-intervention slope) and during treatment (chronic slope). We randomly assigned (1:1) participants with type 2 diabetes, urinary albumin-to-creatinine ratio (UACR) of 50 to under 300 mg/g, and an eGFR of at least 45 ml/min/1.73m2 to receive canagliflozin or guideline-recommended treatment except for SGLT2 inhibitors (control). The first and second primary outcomes were the geometric mean percentage change from baseline in UACR and the change in eGFR slope, respectively. Of 98 randomized participants, 96 received at least one study treatment. The least-squares mean change from baseline in log-transformed geometric mean UACR was significantly greater in the canagliflozin group than the control group (between group-difference, |30.8% (95% confidence interval |42.6 to |16.8). The between-group difference (canagliflozin group – control group) of change in eGFR slope (chronic – pre-intervention) was 4.4 (1.6 to 7.3) ml/min/1.73 m2 per year, which was more pronounced in participants with faster eGFR decline. In summary, canagliflozin reduced albuminuria and the participant-specific natural course of eGFR decline in participants with type 2 diabetes and microalbuminuria. Thus, the CANPIONE study suggests that the within-individual change in eGFR slope may be a novel approach to determine the kidney protective potential of new therapies in early stages of CKD. No potential conflict of interest relevant to this article was reported.

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

MDPI Acta Medica Okayama 2313-433X 10 10 2024 Searching Method for Three-Dimensional Puncture Route to Support Computed Tomography-Guided Percutaneous Puncture 251 EN Yusuke Gotoh Faculty of Environmental, Life, Natural Science and Technology, Okayama University Aoi Takeda Graduate School of Natural Science and Technology, Okayama University Koji Masui Department of Radiology, Kyoto Prefectural University of Medicine Koji Sakai Department of Radiology, Kyoto Prefectural University of Medicine Manato Fujimoto Graduate School of Informatics, Osaka Metropolitan University In CT-guided percutaneous punctures-an image-guided puncture method using CT images-physicians treat targets such as lung tumors, liver tumors, renal tumors, and intervertebral abscesses by inserting a puncture needle into the body from the exterior while viewing images. By recognizing two-dimensional CT images prior to a procedure, a physician determines the least invasive puncture route for the patient. Therefore, the candidate puncture route is limited to a two-dimensional region along the cross section of the human body. In this paper, we aim to construct a three-dimensional puncture space based on multiple two-dimensional CT images to search for a safer and shorter puncture route for a given patient. If all puncture routes starting from a target in the three-dimensional space were examined from all directions (the brute-force method), the processing time to derive the puncture route would be very long. We propose a more efficient method for three-dimensional puncture route selection in CT-guided percutaneous punctures. The proposed method extends the ray-tracing method, which quickly derives a line segment from a given start point to an end point on a two-dimensional plane, and applies it to three-dimensional space. During actual puncture route selection, a physician can use CT images to derive a three-dimensional puncture route that is safe for the patient and minimizes the puncture time. The main novelty is that we propose a method for deriving a three-dimensional puncture route within the allowed time in an actual puncture. The main goal is for physicians to select the puncture route they will use in the actual surgery from among the multiple three-dimensional puncture route candidates derived using the proposed method. The proposed method derives a three-dimensional puncture route within the allowed time in an actual puncture. Physicians can use the proposed method to derive a new puncture route, reducing the burden on patients and improving physician skills. In the evaluation results of a computer simulation, for a 3D CT image created by combining 170 two-dimensional CT images, the processing time for deriving the puncture route using the proposed method was approximately 59.4 s. The shortest length of the puncture route from the starting point to the target was between 20 mm and 22 mm. The search time for a three-dimensional human body consisting of 15 CT images was 4.77 s for the proposed method and 2599.0 s for a brute-force method. In a questionnaire, physicians who actually perform puncture treatments evaluated the candidate puncture routes derived by the proposed method. We confirmed that physicians could actually use these candidates as a puncture route. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 Pediatric Severe Febrile Thrombocytopenia Syndrome: A Case Report and Literature Review 401 405 EN Yusuke Toyota Department of Pediatrics, NHO Iwakuni Clinical Center Kazuhiro Uda Department of Pediatrics, NHO Iwakuni Clinical Center Komei Shirabe Yamaguchi Prefectural Institute of Public Health and Environment Tadashi Moriwake Department of Pediatrics, NHO Iwakuni Clinical Center Case Report 10.18926/AMO/67664 Severe febrile thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease that is endemic in parts of eastern Asia. Few pediatric cases have been reported. We describe a case of SFTS in a seven-year-old girl who presented with prolonged fever and gastrointestinal symptoms. Leukopenia and thrombocytopenia on hematology, and a history of outdoor activity led us to diagnose SFTS, although the patient had no tick bite marks. We also review the literature and discuss the characteristics of pediatric SFTS. Physicians should consider SFTS in the differential diagnosis of fever with thrombocytopenia in children living in endemic areas. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 0815-9319 39 12 2024 Rates and risk factors of bleeding after gastric endoscopic submucosal dissection with continuous warfarin or 1]day withdrawal of direct oral anticoagulants 2760 2766 EN Shoichiro Hirata Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenta Hamada Department of Practical Gastrointestinal Endoscopy, Okayama University Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Mouri Department of Gastroenterology and Hepatology, Kurashiki Central Hospital Koji Miyahara Department of Internal Medicine, Hiroshima City Hospital Takao Tsuzuki Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital Kenji Yamauchi Department of Gastroenterology, Mitoyo General Hospital Sayo Kobayashi Department of Internal Medicine, Fukuyama City Hospital Sakuma Takahashi Department of Gastroenterology, Kagawa Prefectural Central Hospital Ryuta Takenaka Department of Internal Medicine, Tsuyama Chuo Hospital Shinichiro Hori Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital Masafumi Inoue Department of Gastroenterology, Japanese Red Cross Okayama Hospital Tatsuya Toyokawa Department of Gastroenterology, National Hospital Organization Fukuyama Medical Center Mamoru Nishimura Department of Internal Medicine, Okayama City Hospital Shuhei Ishiyama Department of Internal Medicine, Okayama Saiseikai General Hospital Jiro Miyaike Department of Internal Medicine, Saiseikai Imabari Hospital Ryo Kato Department of Gastroenterology, National Hospital Organization Iwakuni Clinical Center Minoru Matsubara Department of Internal Medicine, Sumitomo Besshi Hospital Naoko Yunoki Department of Internal Medicine, Akaiwa Medical Association Hospital Hiromitsu Kanzaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, Okayama University Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideki Ishikawa Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Gut Study Group Background and Aim: The 2017 Japanese guidelines recommend continuing warfarin therapy during the perioperative period or discontinuing direct oral anticoagulants (DOACs) only on the day of endoscopic submucosal dissection for early gastric cancer. However, their safety has not been sufficiently explored. This study aimed to validate this management method.<br> Methods: This retrospective, multicenter study analyzed the characteristics and outcomes of patients who underwent gastric endoscopic submucosal dissection between July 2017 and June 2019. The patients were categorized according to the use of warfarin or DOACs.<br> Results: Among the 62 eligible patients, 53 (85%) were male (median age, 76 years). Warfarin was used in 10 patients (16%) and DOACs in 52 patients (84%). Fourteen patients taking DOACs (27%) used concomitant antiplatelet agents, with seven patients (13%) continuing treatment at the time of the endoscopic procedure. No postprocedural bleeding occurred in patients receiving warfarin (0%), whereas 10 cases (19%) of bleeding occurred in patients receiving DOACs: rivaroxaban, 0% (0/22); dabigatran, 0% (0/2); edoxaban, 43% (6/14); and apixaban, 29% (4/14). The type of anticoagulant (P < 0.01) and continuation of antiplatelet therapy (P = 0.02) were risk factors for postprocedural bleeding in patients receiving DOACs. Intraprocedural bleeding requiring transfusion or symptomatic thromboembolic events were not reported.<br> Conclusions: Continuous warfarin therapy is preferred. DOAC withdrawal 1 day before a procedure is associated with a high bleeding rate, which may differ for different types of anticoagulants. The continuation of antiplatelet medications in patients receiving DOACs carries a high risk of bleeding and is a future challenge. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9059 12 8 2024 Surface Pre-Reacted Glass-Ionomer Eluate Suppresses Osteoclastogenesis through Downregulation of the MAPK Signaling Pathway 1835 EN Janaki Chandra Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Shin Nakamura Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoru Shindo Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Elizabeth Leon Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Maria Castellon Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Maria Rita Pastore Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Alireza Heidari Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Lukasz Witek Biomaterials Division, NYU Dentistry Paulo G. Coelho Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami Toshiyuki Nakatsuka R&D Department, Shofu Inc. Toshihisa Kawai Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Surface pre-reacted glass-ionomer (S-PRG) is a new bioactive filler utilized for the restoration of decayed teeth by its ability to release six bioactive ions that prevent the adhesion of dental plaque to the tooth surface. Since ionic liquids are reported to facilitate transepithelial penetration, we reasoned that S-PRG applied to root caries could impact the osteoclasts (OCs) in the proximal alveolar bone. Therefore, this study aimed to investigate the effect of S-PRG eluate solution on RANKL-induced OC-genesis and mineral dissolution in vitro. Using RAW264.7 cells as OC precursor cells (OPCs), TRAP staining and pit formation assays were conducted to monitor OC-genesis and mineral dissolution, respectively, while OC-genesis-associated gene expression was measured using quantitative real-time PCR (qPCR). Expression of NFATc1, a master regulator of OC differentiation, and the phosphorylation of MAPK signaling molecules were measured using Western blotting. S-PRG eluate dilutions at 1/200 and 1/400 showed no cytotoxicity to RAW264.7 cells but did significantly suppress both OC-genesis and mineral dissolution. The same concentrations of S-PRG eluate downregulated the RANKL-mediated induction of OCSTAMP and CATK mRNAs, as well as the expression of NFATc1 protein and the phosphorylation of ERK, JNK, and p38. These results demonstrate that S-PRG eluate can downregulate RANKL-induced OC-genesis and mineral dissolution, suggesting that its application to root caries might prevent alveolar bone resorption. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 115 10 2024 Overcoming immunotherapy resistance and inducing abscopal effects with boron neutron immunotherapy (B-NIT) 3231 3247 EN Takuya Fujimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Osamu Yamasaki Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Noriyuki Kanehira Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hirokazu Matsushita Division of Translational Oncoimmunology, Aichi Cancer Center Research Institute Yoshinori Sakurai Institute for Integrated Radiation and Nuclear Science, Kyoto University Naoya Kenmotsu Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryo Mizuta Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Natsuko Kondo Institute for Integrated Radiation and Nuclear Science, Kyoto University Takushi Takata Institute for Integrated Radiation and Nuclear Science, Kyoto University Mizuki Kitamatsu Faculty of Science and Engineering, Kindai University Kazuyo Igawa Neutron Therapy Research Center, Okayama University Atsushi Fujimura Neutron Therapy Research Center, Okayama University Yoshihiro Otani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Makoto Shirakawa Neutron Therapy Research Center, Okayama University Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yosuke Togashi Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Minoru Suzuki Institute for Integrated Radiation and Nuclear Science, Kyoto University Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Michiue Neutron Therapy Research Center, Okayama University Immune checkpoint inhibitors (ICIs) are effective against many advanced malignancies. However, many patients are nonresponders to immunotherapy, and overcoming this resistance to treatment is important. Boron neutron capture therapy (BNCT) is a local chemoradiation therapy with the combination of boron drugs that accumulate selectively in cancer and the neutron irradiation of the cancer site. Here, we report the first boron neutron immunotherapy (B-NIT), combining BNCT and ICI immunotherapy, which was performed on a radioresistant and immunotherapy-resistant advanced-stage B16F10 melanoma mouse model. The BNCT group showed localized tumor suppression, but the anti-PD-1 antibody immunotherapy group did not show tumor suppression. Only the B-NIT group showed strong tumor growth inhibition at both BNCT-treated and shielded distant sites. Intratumoral CD8+ T-cell infiltration and serum high mobility group box 1 (HMGB1) levels were higher in the B-NIT group. Analysis of CD8(+) T cells in tumor-infiltrating lymphocytes (TILs) showed that CD62L- CD44(+) effector memory T cells and CD69(+) early-activated T cells were predominantly increased in the B-NIT group. Administration of CD8-depleting mAb to the B-NIT group completely suppressed the augmented therapeutic effects. This indicated that B-NIT has a potent immune-induced abscopal effect, directly destroying tumors with BNCT, inducing antigen-spreading effects, and protecting normal tissue. B-NIT, immunotherapy combined with BNCT, is the first treatment to overcome immunotherapy resistance in malignant melanoma. In the future, as its therapeutic efficacy is demonstrated not only in melanoma but also in other immunotherapy-resistant malignancies, B-NIT can become a new treatment candidate for advanced-stage cancers. No potential conflict of interest relevant to this article was reported.

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

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

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

Wiley Acta Medica Okayama 1360-2322 37 4 2024 Optimising the oral midazolam dose for premedication in people with intellectual disabilities and/or autism spectrum disorder e13265 EN Hitoshi Higuchi Department of Dental Anesthesiology, Okayama University Hospital Kota Miyake Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Saki Miyake Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Maki Fujimoto Department of Dental Anesthesiology, Okayama University Hospital Yukiko Nishioka Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shigeru Maeda Department of Dental Anesthesiology, Okayama University Hospital Takuya Miyawaki Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: In people with intellectual disabilities and/or autism spectrum disorder, oral midazolam (OM) is very effective as premedication for facilitating medical treatment. In this retrospective study, we investigated the optimal dosage of OM for premedication.<br> Methods: Patients with intellectual disability and/or autism spectrum disorder who were given OM as a premedication were selected from anaesthesia records. The primary outcome variable was the dose of OM (mg/kg) required to produce an adequate sedation.<br> Results: The mean OM dose required was 0.32 } 0.10 mg/kg. The required OM dose decreased significantly as age and weight increased, and age and weight were also shown to be significantly associated with the dose of OM in the multivariate linear regression analysis.<br> Conclusion: The dosage of OM to achieve adequate sedation should decrease as the patient ages. Furthermore, adequate sedation can be achieved with even lower doses of OM in obese people. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2405-8440 10 11 2024 Bacterial DNA and serum IgG antibody titer assays for assessing infection of human-pathogenic and dog-pathogenic Porphyromonas species in dogs e31872 EN Masako Tai-Tokuzen Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Takashi Ito Center for Innovative Clinical Medicine, Okayama University Hospital Kazuya Tamura Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruko Hirayama Department of Animal Resources, Advanced Science Research Center, Okayama University Hirohito Ogawa Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin Nakamura Center for Collaborative Research, Department of Oral Science and Translational Research, Nova Southeastern University Keisuke Okubo Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Kazuhiro Omori Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Yamamoto Department of Comprehensive Dentistry, The Center for Graduate Medical Education (Dental Division), Okayama University Hospital Katsumi Mominoki Department of Animal Resources, Advanced Science Research Center, Okayama University Shogo Takashiba Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Periodontal disease is highly prevalent in both humans and dogs. Although there have been reports of cross-infection of periodontopathic bacteria, methods for assessing it have yet to be established. The actual status of cross-infection remains to be seen. The purpose of this study was to evaluate the utility of bacterial DNA and serum immunoglobulin G (IgG) antibody titer assays to assess infection of human-pathogenic and dog-pathogenic Porphyromonas species in dogs. Four experimental beagles were used for establishing methods. Sixty-six companion dogs at veterinary clinics visiting for treatment and prophylaxis of periodontal disease were used and divided into healthy, gingivitis, and periodontitis groups. Periodontal pathogens such as Porphyromonas gingivalis and Porphyromonas gulae were investigated as target bacteria. DNA levels of both bacteria were measured using species-specific primers designed for real-time polymerase chain reaction (PCR). Serum IgG titers of both bacteria were measured by enzyme-linked immunosorbent assay (ELISA).<br> PCR primers were confirmed to have high sensitivity and specificity. However, there was no relationship between the amount of bacterial DNA and the severity of the periodontal disease. In addition, dogs with periodontitis had higher IgG titers against both bacteria compared to dogs in the healthy and gingivitis groups; there was cross-reactivity between the two bacteria. Receiver operating characteristic (ROC) analysis of IgG titers against both bacteria showed high sensitivity (>90 %) and specificity (>75 %). Since both bacteria were distinguished by DNA assays, the combination of these assays may be useful in the evaluation of cross-infection. No potential conflict of interest relevant to this article was reported.

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

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

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

Acta Medica Okayama 2024 ’οRƒXƒ|ƒbƒg—nΪ‚Μ“d‹CE”ME—ΝŠw˜A¬”’l‰πΝ‚ΙŠΦ‚·‚ιŒ€‹† EN Manabu FUKUMOTO Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Co-occurrence of non-alcoholic steatohepatitis exacerbates psoriasis associated with decreased adiponectin expression in a murine model EN Daiki TAKEZAKI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

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

Acta Medica Okayama 2024 Optimal Bowel Preparation Method to Visualize the Distal Ileum via Small Bowel Capsule Endoscopy EN Daisuke KAMETAKA 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 When to intervene the pulmonary artery: Importance of anatomical assessment in the diagnosis of pulmonary artery coarctation EN Eiri KISAMORI 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 Efficacy of gilteritinib in comparison with alectinib for the treatment of ALK-rearranged non-small cell lung cancer EN Chihiro ANDO 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 CDK4/6 signaling attenuates the effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer EN Naofumi HARA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Baishideng Publishing Group Acta Medica Okayama 1007-9327 30 16 2024 Drug-induced mucosal alterations observed during esophagogastroduodenoscopy 2220 2232 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Several features of drug-induced mucosal alterations have been observed in the upper gastrointestinal tract, i.e., the esophagus, stomach, and duodenum. These include pill-induced esophagitis, desquamative esophagitis, worsening of gastroesophageal reflux, chemotherapy-induced esophagitis, proton pump inhibitor-induced gastric mucosal changes, medication-induced gastric erosions and ulcers, pseudomelanosis of the stomach, olmesartan-related gastric mucosal inflammation, lanthanum deposition in the stomach, zinc acetate hydrate tablet-induced gastric ulcer, immune-related adverse event gastritis, olmesartan-asso-ciated sprue-like enteropathy, pseudomelanosis of the duodenum, and lanthanum deposition in the duodenum. For endoscopists, acquiring accurate knowledge regarding these diverse drug-induced mucosal alterations is crucial not only for the correct diagnosis of these lesions but also for differential diag-nosis of other conditions. This minireview aims to provide essential information on drug-induced mucosal alterations observed on esophagogastroduodenoscopy, along with representative endoscopic images. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 0340-5443 77 7 2023 Latitudinal cline in reproductive traits in the red flour beetle Tribolium castaneum 85 EN Kentarou Matsumura Graduate School of Environmental, Life Science and Technology, Okayama University Kyosuke Wakabayashi Graduate School of Environmental, Life Science and Technology, Okayama University Renya Kawakami Faculty of Agriculture, Kagawa University Takahisa Miyatake Graduate School of Environmental, Life Science and Technology, Okayama University Several previous studies have reported geographic variation and/or latitudinal clines of morphological sexual characteristics, but there are few studies that consider reproductive traits that are not morphological. Here, we measured the proportion of females fertilized by males, frequency of reproductive failure in males, and number of female copulations of the red flour beetle Tribolium castaneum collected from fields in Japan to investigate the relationship between reproductive traits and latitude. Our results show substantial differences in the reproductive traits of both sexes among field populations. We identified latitudinal clines for reproductive traits in males, but not females. Moreover, female, but not male, reproductive traits were correlated with body size. Our study suggests that selection for male reproductive traits varies with latitude in T. castaneum. No potential conflict of interest relevant to this article was reported.

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

AME Publishing Company Acta Medica Okayama 2218-6751 12 10 2023 CDK4/6 signaling attenuates the effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer EN Naofumi Hara Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Hirohisa Kano Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Chihiro Ando Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ayako Morita Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tatsuya Nishi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Sachi Okawa Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takamasa Nakasuka Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atsuko Hirabae Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masaya Abe Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Go Makimoto Center for Clinical Oncology, Okayama University Hospital Masanori Fujii Department of Allergy and Respiratory Medicine, Okayama University Hospital Toshio Kubo Department of Allergy and Respiratory Medicine, Okayama University Hospital Kadoaki Ohashi Department of Allergy and Respiratory Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Masahiro Tabata Center for Clinical Oncology, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Background: Epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletion and exon 21 L858R, are driver oncogenes of non-small cell lung cancer (NSCLC), with EGFR tyrosine kinase inhibitors (TKIs) being effective against EGFR-mutant NSCLC. However, the efficacy of EGFR-TKIs is transient and eventually leads to acquired resistance. Herein, we focused on the significance of cell cycle factors as a mechanism to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC before the emergence of acquired resistance.<br> Methods: Using several EGFR-mutant cell lines, we investigated the significance of cell cycle factors to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC.<br> Results: In several EGFR-mutant cell lines, certain cancer cells continued to proliferate without EGFR signaling, and the cell cycle regulator retinoblastoma protein (RB) was not completely dephosphorylated. Further inhibition of phosphorylated RB with cyclin-dependent kinase (CDK) 4/6 inhibitors, combined with the EGFR-TKI osimertinib, enhanced G0/G1 cell cycle accumulation and growth inhibition of the EGFR-mutant NSCLC in both in vitro and in vivo models. Furthermore, residual RB phosphorylation without EGFR signaling was maintained by extracellular signal-regulated kinase (ERK) signaling, and the ERK inhibition pathway showed further RB dephosphorylation.<br> Conclusions: Our study demonstrated that the CDK4/6-RB signal axis, maintained by the MAPK pathway, attenuates the efficacy of EGFR-TKIs in EGFR-mutant NSCLC, and targeting CDK4/6 enhances this efficacy. Thus, combining CDK4/6 inhibitors and EGFR-TKI could be a novel treatment strategy for TKI-naïve EGFR-mutant NSCLC. 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.

MDPI Acta Medica Okayama 2072-6694 16 7 2024 Copy Number Analysis of 9p24.1 in Classic Hodgkin Lymphoma Arising in Immune Deficiency/Dysregulation 1298 EN Kumiko Ohsawa Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Shuji Momose Department of Pathology, Saitama Medical Center, Saitama Medical University Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yuka Gion Department of Medical Technology, Faculty of Health Sciences, Ehime Prefectural University of Health Sciences Keisuke Sawada Department of Pathology, Saitama Medical Center, Saitama Medical University Morihiro Higashi Department of Pathology, Saitama Medical Center, Saitama Medical University Michihide Tokuhira Department of Hematology, Japan Community Health Care Organization Saitama Medical Center Jun-Ichi Tamaru Department of Pathology, Saitama Medical Center, Saitama Medical University Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences A subset of patients with rheumatoid arthritis receiving methotrexate develop immune deficiencies and dysregulation-associated lymphoproliferative disorders. Patients with these disorders often exhibit spontaneous regression after MTX withdrawal; however, chemotherapeutic intervention is frequently required in patients with classic Hodgkin lymphoma arising in immune deficiency/dysregulation. In this study, we examined PD-L1 expression levels and 9p24.1 copy number alterations in 27 patients with classic Hodgkin lymphoma arising from immune deficiency/dysregulation. All patients demonstrated PD-L1 protein expression and harbored 9p24.1 copy number alterations on the tumor cells. When comparing clinicopathological data and associations with 9p24.1 copy number features, the copy gain group showed a significantly higher incidence of extranodal lesions and clinical stages than the amplification group. Notably, all cases in the amplification group had latency type II, while 6/8 (75%) in the copy gain group had latency type II, and 2/8 (25%) had latency type I. Thus, a subset of the copy-gain group demonstrated more extensive extranodal lesions and higher clinical stages. This finding speculates the presence of a genetically distinct subgroup within the group of patients who develop immune deficiencies and dysregulation-associated lymphoproliferative disorders, which may explain certain characteristic features. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 13 7 2024 A Prospective Observational Study on Gastric Endoscopic Submucosal Dissection under Continuous Administration of Antithrombotic Agents 1886 EN Daisuke Kawai Department of Gastroenterology, Tsuyama Chuo Hospital Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryuta Takenaka Department of Gastroenterology, Tsuyama Chuo Hospital Taisuke Obata Department of Gastroenterology, Tsuyama Chuo Hospital Takashi Yamamoto Department of Gastroenterology, Tsuyama Chuo Hospital Shoichiro Hirata Department of Gastroenterology, Tsuyama Chuo Hospital Ko Miura Department of Gastroenterology, Tsuyama Chuo Hospital Koji Takemoto Department of Gastroenterology, Tsuyama Chuo Hospital Hirofumi Tsugeno Department of Gastroenterology, Tsuyama Chuo Hospital Shigeatsu Fujiki Department of Gastroenterology, Tsuyama Chuo Hospital Background: This study aimed to assess the completion rate and postoperative bleeding incidence of endoscopic submucosal dissection (ESD) for gastric tumors under continuous antithrombotic therapy. Methods: A prospective observational study was conducted including 88 patients with 100 gastric lesions who underwent gastric endoscopic submucosal dissection (ESD) and received continuous antithrombotic therapy. Additionally, retrospective data on gastric ESD in 479 patients with 534 lesions who did not receive antithrombotic therapy were collected for comparison. Results: The en bloc resection rates (100% in the continuous antithrombotic therapy group vs. 100% in the non-antithrombotic therapy group) and complete resection rates (97.0% vs. 96.3%, respectively) were high and comparable between the groups. No significant differences were found in the specimen size or procedure time. Perforation rates were low (0% vs. 2.3%, respectively) and were not significantly different between the groups. However, postoperative bleeding occurred significantly more frequently in the continuous antithrombotic therapy group (10.2% vs. 4.2%, respectively) than in the non-antithrombotic therapy group. The subgroup analysis revealed a higher incidence of postoperative bleeding in patients receiving thienopyridine derivatives. Conclusions: Continuous administration of antithrombotic agents, especially thienopyridines, increased the risk of postprocedural hemorrhage following gastric ESD. These findings support the need for careful consideration of pharamcological management before ESD, aligning with the current guidelines. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 The Roles of Neuropeptide Y in Respiratory Disease Pathogenesis via the Airway Immune Response 95 106 EN Junko Itano Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuaki Miyahara Department of Allergy and Respiratory Medicine, Okayama University Hospital Review 10.18926/AMO/66912 The lungs are very complex organs, and the respiratory system performs the dual roles of repairing tissue while protecting against infection from various environmental stimuli. Persistent external irritation disrupts the immune responses of tissues and cells in the respiratory system, ultimately leading to respiratory disease. Neuropeptide Y (NPY) is a 36-amino-acid polypeptide and a neurotransmitter that regulates homeostasis. The NPY receptor is a seven-transmembrane-domain G-protein-coupled receptor with six subtypes (Y1, Y2, Y3, Y4, Y5, and Y6). Of these receptors, Y1, Y2, Y4, and Y5 are functional in humans, and Y1 plays important roles in the immune responses of many organs, including the respiratory system. NPY and the Y1 receptor have critical roles in the pathogenesis of asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis. The effects of NPY on the airway immune response and pathogenesis differ among respiratory diseases. This review focuses on the involvement of NPY in the airway immune response and pathogenesis of various respiratory diseases. No potential conflict of interest relevant to this article was reported.

‰ͺŽR‘εŠw‘εŠw‰@ƒwƒ‹ƒXƒVƒXƒeƒ€“‡‰ΘŠwŒ€‹†‰Θ Acta Medica Okayama 2436-3227 4 2024 ƒAƒgƒs[«”畆‰Š‚Μ‚ ‚鐬l‚ͺŒoŒ±‚·‚ι‚©‚δ‚έ‚ΙŠΦ‚·‚ι‹LqŒ€‹† 9 18 EN Yuki HIRAMI Faculty of Health Sciences, Okayama University Kanako FUJIMOTO Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masahide KODA Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nahoko HARADA Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University 10.18926/interdisciplinary/66893 Background: Atopic Dermatitis (AD) is a chronic inflammatory skin disease characterized by intense itching, significantly impacting patients' psychosocial well-being worldwide. Objective: This study aimed to elucidate the multifaceted and multilayered burden of itch in adult AD patients, exploring strategies to capture the complexity of the disease and its symptoms comprehensively. Methods: The study utilized an array of Patient Reported Outcome (PRO) measures and conducted an exploratory analysis of patients' subjective descriptions of their itch experiences. Results: Twenty-three participants (female: n=16) were enrolled in the study. The Analyses revealed that none of the participants experienced in the same way about physical, emotional, and psychological burden of itch and limitation in social life. Additionally, it was found that PROs capture only partial aspects of itch and do not provide a comprehensive understanding. Discussion: The findings highlight the necessity of employing multiple PROs and conducting in-depth patient interviews to understand the daily life challenges associated with itch. The potential of interdisciplinary research to address the complex burden of itch in AD patients is also emphasized. Conclusion: A comprehensive understanding of the symptom of itch in AD patients requires the use of multiple PROs. 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.

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

Wiley Acta Medica Okayama 2189-7948 25 2 2024 Treatment interruption in hypertensive patients during the COVID-19 pandemic: An interrupted time series analysis using prescription data in Okayama, Japan 102 109 EN Naoko Nakamura Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Naomi Matsumoto Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsaku Hayase Academic Affairs Division, Okayama University Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: The COVID- 19 pandemic has impacted healthcare behaviors, leading to fewer pediatric visits in Japan and potentially fewer visits by adult patients. However, existing Japanese studies on treatment interruptions have generally relied on questionnaire- based methods. In this study, we assessed the impact of the pandemic on antihypertensive treatment interruption using real- world prescription data. <br> Methods: We conducted an interrupted time series analysis using the National Health Insurance Database in Okayama Prefecture, Japan. Participants included individuals aged 40-69 years with at least one antihypertensive prescription between 2018 and 2020. Treatment interruption was defined as a 3- month or longer gap in prescriptions after medication depletion. We used segmented Poisson regression with models unadjusted and adjusted for seasonality and over- dispersion to assess monthly treatment interruptions before and after Japan's April 2020 emergency. <br> Results: During the study period, 23.0% of 55,431 participants experienced treatment interruptions. Cyclical fluctuations in interruptions were observed. The crude analysis indicated a 1.2 - fold increase in treatment interruptions following the pandemic; however, the adjusted models showed no significant changes. Even among higher- risk groups, such as women, younger adults, and those with shorter prescriptions, no significant alterations were observed. <br> Conclusion: We found no significant impact of the COVID- 19 pandemic on antihypertensive treatment interruption in Okayama Prefecture. The less severe outbreak in the area or increased use of telemedicine and extended prescriptions may have contributed to treatment continuity. Further research is needed using a more stable and comprehensive database, broader regional data, and detailed prescription records to validate and extend our findings. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1869-2044 73 1 2023 Exploratory study of volatile fatty acids and the rumen-and-gut microbiota of dairy cows in a single farm, with respect to subclinical infection with bovine leukemia virus 31 EN Takehito Suzuki School of Veterinary Medicine, Azabu University Hironobu Murakami School of Veterinary Medicine, Azabu University Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Reiichiro Sato Faculty of Agriculture, University of Miyazaki Iyo Takemura-Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Masaya Ogata School of Veterinary Medicine, Azabu University Kazuyuki Sogawa School of Veterinary Medicine, Azabu University Hiroho Ishida School of Veterinary Medicine, Azabu University Apichart Atipairin School of Pharmacy, Walailak University Osamu Matsushita Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Makoto Nagai School of Veterinary Medicine, Azabu University Background Subclinical infection with bovine leukemia virus (BLV) in cows can cause economic losses in milk and meat production in many countries, as BLV-related negative effects. The volatile fatty acids (VFAs) and microbiota present in the digestive tracts of cows can contribute to cow health. Here, we exploratorily investigated the VFAs and microbiota in the rumen and gut with respect to subclinical BLV infection using cows housed at a single farm.<br> Results We analyzed a herd of 38 cows kept at one farm, which included 15 uninfected and 23 BLV-infected cows. First, the analysis of the VFAs in the rumen, gut, and blood revealed an absence of statistically significant differences between the uninfected and BLV-infected groups. Thus, BLV infection did not cause major changes in VFA levels in all tested specimens. Next, we analyzed the rumen and gut microbiota. The analysis of the microbial diversity revealed a modest difference between the uninfected and BLV-infected groups in the gut; by contrast, no differences were observed in the rumen. In addition, the investigation of the bacteria that were predominant in the uninfected and BLV-infected groups via a differential abundance analysis showed that no significant bacteria were present in either of the microbiota. Thus, BLV infection possibly affected the gut microbiota to a small extent. Moreover, bacterial associations were compared between the uninfected and BLV-infected groups. The results of this analysis suggested that BLV infection affected the equilibrium of the bacterial associations in both microbiota, which might be related to the BLV-related negative effects. Thus, BLV infection may negatively affect the equilibrium of bacterial associations in both microbiota.<br> Conclusions Subclinical BLV infection is likely to affect the rumen and gut microbiota, which may partly explain the BLV-related negative effects. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-1335 150 2 2024 Clinical characteristics of patients treated with immune checkpoint inhibitors in EGFR-mutant non-small cell lung cancer: CS-Lung-003 prospective observational registry study 89 EN Tadahiro Kuribayashi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kadoaki Ohashi Department of Allergy and Respiratory Medicine, Okayama University Hospital Kazuya Nishii Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kiichiro Ninomiya Department of Allergy and Respiratory Medicine, Okayama University Hospital Yukari Tsubata Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Faculty of Medicine, Shimane University Nobuhisa Ishikawa Department of Respiratory Medicine, Hiroshima Prefectural Hospital Masahiro Kodani Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University Nobuhiro Kanaji Department of Internal Medicine, Division of Hematology, Rheumatology, and Respiratory Medicine, Faculty of Medicine, Kagawa University Masahiro Yamasaki Department of Respiratory Medicine, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital Kazunori Fujitaka Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences Shoichi Kuyama Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center Nagio Takigawa Department of Internal Medicine 4, Kawasaki Medical School Nobukazu Fujimoto Department of Medical Oncology, Okayama Rosai Hospital Tetsuya Kubota Department of Respiratory Medicine and Allergology, Kochi University Hospital Masaaki Inoue Department of Chest Surgery, Shimonoseki City Hospital Keiichi Fujiwara Department of Respiratory Medicine, NHO Okayama Medical Center Shingo Harita Department of Internal Medicine, Okayama Saiseikai General Hospital Ichiro Takata Internal Medicine, Fukuyama City Hospital Kenji Takada Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sachi Okawa Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Katsuyuki Hotta Department of Allergy and Respiratory Medicine, Okayama University Hospital Purpose Immune checkpoint inhibitors (ICIs) are ineffective against epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical characteristics of patients who were treated or not treated with ICIs, and of those who benefit from immunotherapy in EGFR-mutant NSCLC.<br> Methods We analyzed patients with unresectable stage III/IV or recurrent NSCLC harboring EGFR mutations using a prospective umbrella-type lung cancer registry (CS-Lung-003).<br> Results A total of 303 patients who met the eligibility criteria were analyzed. The median age was 69 years; 116 patients were male, 289 had adenocarcinoma, 273 had major mutations, and 67 were treated with ICIs. The duration of EGFR-TKI treatment was longer in the Non-ICI group than in the ICI group (17.1 vs. 12.7 months, p < 0.001). Patients who received ICIs for more than 6 months were categorized into the durable clinical benefit (DCB) group (24 patients), and those who received ICIs for less than 6 months into the Non-DCB group (43 patients). The overall survival in the DCB group exhibited longer than the Non-DCB group (69.3 vs. 47.1 months), and an equivalent compared to that in the Non-ICI group (69.3 vs. 68.9 months). Multivariate analysis for time to next treatment (TTNT) of ICIs showed that a poor PS was associated with a shorter TTNT [hazard ratio (HR) 3.309; p < 0.001]. Patients who were treated with ICIs and chemotherapy combination were associated with a longer TTNT (HR 0.389; p = 0.003). In addition, minor EGFR mutation was associated with a long TTNT (HR 0.450; p = 0.046).<br> Conclusion ICIs were administered to only 22% of patients with EGFR-mutated lung cancer, and they had shorter TTNT of EGFR-TKI compared to other patients. ICI treatment should be avoided in EGFR mutated lung cancer with poor PS but can be considered for lung cancer with EGFR minor mutations. Pathological biomarker to predict long-term responders to ICI are needed.<br> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Ectopic Breast Cancer Arising within an Axillary Lymph Node 89 93 EN Kei Toshima Department of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Midori Filiz Nishimura Department of Molecular Hematopathology, Graduate School of Health Sciences, Okayama University Yoko Suzuki Department of Breast and Endocrine Surgery, Okayama University Hospital Shogo Nakamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Maya Uno Department of Breast and Endocrine Surgery, Okayama University Hospital Ryo Yoshioka Department of Breast and Endocrine Surgery, Okayama University Hospital Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Tsuguo Iwatani Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyuki Yanai Department of Diagnostic Pathology, Okayama University Hospital Case Report 10.18926/AMO/66676 We report our experience with the diagnosis and treatment of an ectopic breast cancer arising within an axillary lymph node. The patient was a 65-year-old woman diagnosed breast cancer and axillary lymph node metastasis. We performed a partial mastectomy and axillary lymph node dissection. Postoperative pathology revealed no malignant lesions in the breast; however, a nodule in one of axillary lymph nodes had mixed benign and malignant components, leading to a diagnosis of invasive ductal carcinoma derived from ectopic mammary tissue. This case represents a very rare form of breast cancer, and the malignancy was difficult to distinguish from metastasis. No potential conflict of interest relevant to this article was reported.

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

‰ͺŽR‘εŠw”_Šw•” Acta Medica Okayama 2186-7755 113 2024 Ϊ‚¬–Ψ‚Ι‚ζ‚ιŠJ‰Τ—U“±‚ΜƒAƒuƒ‰ƒi‰Θμ•¨‚ΜˆηŽν‚¨‚ζ‚ΡΜŽν‚Φ‚Μ—˜—p 55 59 EN Ko Motoki Course of Applied Plant Science Grafting-induced flowering has the potential to be applied to plant breeding and seed production, to shorten the time needed for floral induction, and to expand the environment in which seed production is possible. However, it is difficult to induce flowering by grafting in some crop species, which currently limits the use of this technique to specific plant species. We have established a technique for inducing flowering in cabbage (Brassica oleracea L.) by grafting, which had hitherto been considered difficult, by clarifying the causes of different flowering responses caused by various rootstocks. This article introduces the key factors for the floral induction of cabbage by grafting and its potential application to the breeding and seed production of cruciferous crops. It was observed that cabbage grafted onto B. oleracea rootstocks did not flower at all, while cabbage grafted onto some accessions of Raphanus sativus rootstocks did flower. Furthermore, the ability of R. sativus to induce flowering of grafted cabbage varied even within the species. Immunoblotting analysis of the FLOWERING LOCUS T (FT) protein, a main component of florigen, revealed that floral induction was quantitatively correlated with the level of accumulated FT protein in the grafted scion. It was concluded that increasing the total amount of FT protein produced in the rootstock is important for the stable floral induction of the grafted cabbage, and this can be accomplished by increasing FT transcription and the leaf area of the rootstock. Field cultivation experiments with cabbage progenies obtained by the grafting method indicated the direct applicability of this method to breeding and seed production in cruciferous crops. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Abnormal Vaginal Cytology after Total Laparoscopic Hysterectomy in Patients with Cervical Intraepithelial Neoplasia 627 634 EN Yumi Hibino Department of Gynecologic Oncology, NHO Shikoku Cancer Center Mika Okazawa-Sakai Department of Gynecologic Oncology, NHO Shikoku Cancer Center Takanori Yokoyama Department of Gynecologic Oncology, NHO Shikoku Cancer Center Etsuko Fujimoto Department of Gynecologic Oncology, NHO Shikoku Cancer Center Shinichi Okame Department of Gynecologic Oncology, NHO Shikoku Cancer Center Norihiro Teramoto Department of Pathology, NHO Shikoku Cancer Center Kazuhiro Takehara Department of Gynecologic Oncology, NHO Shikoku Cancer Center Original Article 10.18926/AMO/66155 To explore the incidence of abnormal vaginal cytology after total laparoscopic hysterectomy for the treatment of cervical intraepithelial neoplasia 3, we retrospectively analyzed the medical records of patients treated at NHO Shikoku Cancer Center (Japan) in 2014-2019. The cases of 99 patients who underwent a laparoscopic (n=36) or open (n=63) hysterectomy and postoperative follow-up were examined. Abnormal vaginal cytology was detected in 13.9% (5/36) of the laparoscopic-surgery (LS) group and 14.3% (9/63) of the open-surgery (OS) group. A vaginal biopsy was performed at the physiciansf discretion; one LS patient and six OS patients were diagnosed with vaginal intraepithelial neoplasia. The cumulative incidence of abnormal vaginal cytology at 3 years post-hysterectomy was 21.4% (LS group) and 20.5% (OS group), a nonsignificant difference. A multivariate analysis showed that age > 50 years was the only independent risk factor for abnormal vaginal cytology among the covariates examined including age; body mass index; histories of vaginal delivery, abdominal surgery, and smoking; and surgical approach (hazard ratio 8.11; 95% confidence interval 1.73-37.98; p=0.01). These results suggest that the occurrence of abnormal vaginal cytology after a hysterectomy may not be influenced by the laparoscopic procedure but is associated with older age. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Assessment of factors affecting the motility and viability of frozen-thawed bull spermatozoa EN NGUYEN THANH HAI Graduate School of Environmental and Life Science, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Overcoming cancer‑associated fibroblast‑induced immunosuppression by anti‑interleukin‑6 receptor antibody EN Noriyuki NISHIWAKI 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 Significant Delayed Activation on the Right Ventricular Outflow Tract Represents Complete Right Bundle -Branch Block Pattern in Brugada Syndrome EN Yoshimasa MORIMOTO 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 SPRED2: A Novel Regulator of Epithelial-Mesenchymal Transition and Stemness in Hepatocellular Carcinoma Cells EN TONG GAO Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Georg Thieme Verlag KG Acta Medica Okayama 2364-3722 10 05 2022 Resection depth for small colorectal polyps comparing cold snare polypectomy, hot snare polypectomy and underwater endoscopic mucosal resection E602 E608 EN Junki Toyosawa Department of Gastroenterology, Okayama University Hospital Yasushi Yamasaki Department of Gastroenterology, Okayama University Hospital Tsuyoshi Fujimoto Department of Gastroenterology, Iwakuni Clinical Center Shouichi Tanaka Department of Gastroenterology, Iwakuni Clinical Center Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Hiroyuki Okada Department of Gastroenterology, Okayama University Hospital Background and study aims Small colorectal polyps are removed by various methods, including cold snare polypectomy (CSP), hot snare polypectomy (HSP), and underwater endoscopic mucosal resection (UEMR), but the indications for using these methods are unclear. We retrospectively assessed the efficacy of CSP, HSP, and UEMR for small polyps, focusing on the depth of the resected specimens.<br> Patients and methods Outpatients with non-pedunculated small polyps (endoscopically diagnosed as 6 to 9 mm), resected by two endoscopists between July 2019 and September 2020, were enrolled. We histologically evaluated the specimens resected via CSP, HSP, and UEMR. The main outcome was the containment rate of the muscularis mucosa (MM) and submucosa (SM) tissues.<br> Results Forty polyps resected via CSP (n = 14), HSP (n = 12), or UEMR (n = 14) were enrolled after excluding 13 polyps with resection depths that were difficult to determine. The rates of specimens containing MM and SM tissue differed significantly (57 % and 29 % for CSP, 92 % and 83 % for HSP, and 100 % and 100 % for UEMR, respectively (P = 0.005 for MM and P < 0.001 for SM tissue). Multiple logistic regression analysis showed UEMR was an independent factor relating to the containment of SM tissue. The thickness of SM tissue by CSP, HSP, and UEMR were 52 ƒΚm, 623 ƒΚm, and 1119 ƒΚm, respectively (P < 0.001). The thickness by CSP was significantly less than those by HSP and UEMR (P < 0.001, Bonferroni correction).<br> Conclusions UEMR could be the best method to contain SM tissue without injection. Further studies are needed to evaluate the indication of UEMR for small polyps. 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 ƒΚm. 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.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Neurological Analysis Based on the Terminal End of the Spinal Cord and the Narrowest Level of Injured Spine in Thoracolumbar Spinal Injuries 499 509 EN Yuji Hatakeyama Department of Orthopaedic Surgery, Akita Red Cross Hospital Michio Hongo Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Tadato Kido Department of Orthopaedic Surgery, Akita Rosai Hospital Masakazu Urayama Department of Orthopaedic Surgery, Ogachi Central Hospital Yuji Kasukawa Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Hiroshi Sasaki Department of Orthopaedic Surgery, Noshiro Kousei Medical Center Toshiaki Aizawa Department of Orthopaedic Surgery, Kitaakita Municipal Hospital Daisuke Kudo Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Ryota Kimura Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Yuichi Ono Department of Orthopaedic Surgery, Akita Red Cross Hospital Fumihito Kasama Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Naohisa Miyakoshi Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Original Article 10.18926/AMO/65972 This study aimed to clarify neurological differences among the epiconus, conus medullaris, and cauda equina syndromes. Eighty-seven patients who underwent surgery for acute thoracolumbar spinal injuries were assessed. We defined the epiconus as the region from the terminal end of the spinal cord to the proximal 1.0 to 2.25 vertebral bodies, the conus medullaris as the region proximal to < 1.0 vertebral bodies, and the cauda equina as the distal part of the nerve roots originating from the spinal cord. On the basis of the distance from the terminal end of the spinal cord to the narrowest level of the spinal canal, the narrowest levels were ordered as follows: the epiconus followed by the conus medullaris and cauda equina. The narrowest levels were the epiconus in 22 patients, conus medullaris in 37 patients, and cauda equina in 25 patients. On admission, significantly more patients had a narrowed epiconus of Frankel grades A-C than a narrowed cauda equina. At the final follow-up, there were no significant differences in neurological recovery among those with epiconus, conus medullaris, or cauda equina syndrome. Anatomically classifying the narrowest lesion is useful for clarifying the differences and similarities among these three syndromes. No potential conflict of interest relevant to this article was reported.

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

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.

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

Oxford University Press (OUP) Acta Medica Okayama 2047-4873 28 18 2021 Incremental prognostic value of non-alcoholic fatty liver disease over coronary computed tomography angiography findings in patients with suspected coronary artery disease 2059 2066 EN Keishi Ichikawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Osawa Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center Takashi Miki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hironobu Toda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Yoshida Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aims@This study aimed to investigate additional risk stratification benefits of hepatic steatosis (HS) concurrently assessed during coronary computed tomography angiography (CTA) in a large patient cohort with suspected stable coronary artery disease (CAD).<br> Methods and results@In this prospective study, 1148 Japanese outpatients without a history of CAD who underwent coronary CTA for suspected stable CAD (mean age 64 } 14 years) were included. HS, defined on CT as a hepatic-to-spleen attenuation ratio of <1.0, was examined just before the evaluation of adverse CTA findings, defined as obstructive and/or high-risk plaque. The major adverse cardiac events (MACE) were the composite of cardiac death, acute coronary syndrome, and late revascularization. The incremental predictive value of HS was evaluated using the global ƒΤ2 test and C-statistic. HS was identified in 247 (22%) patients. During a median follow-up of 3.9 years, MACE was observed in 40 (3.5%) patients. HS was significantly associated with MACE in a model that included adverse CTA findings (hazard ratio 4.01, 95% confidence interval 2.12–7.59, P < 0.001). By adding HS to the Framingham risk score and adverse CTA findings, the global ƒΤ2 score and C-statistic significantly increased from 29.0 to 49.5 (P < 0.001) and 0.74 to 0.81 (P = 0.026), respectively. In subgroup analyses in patients with diabetes mellitus and metabolic syndrome, HS had significant additive predictive value for MACE over the Framingham risk score and adverse CTA findings.<br> Conclusion@In patients with suspected stable CAD, concurrent evaluation of HS during coronary CTA enables more accurate detection of patients at higher risk of MACE. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1462-8902 24 8 2022 Rationale, design and baseline characteristics of the effect of canagliflozin in patients with type 2 diabetes and microalbuminuria in the Japanese population: The CANPIONE study 1429 1438 EN Satoshi Miyamoto Center for Innovative Clinical Medicine, Okayama University Hospital Hiddo J. L. Heerspink Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen Dick de Zeeuw Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen Masao Toyoda Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine Daisuke Suzuki Suzuki Diadetes Clinic Takashi Hatanaka Department of Diabetes and Endocrinology, National Hospital Organization Fukuyama Medical Center Tohru Nakamura Diabetes Internal Medicine, Sumitomo Besshi Hospital Shinji Kamei Department of Diabetic Medicine, Kurashiki Central Hospital Satoshi Murao Department of Diabetes and Endocrinology, Takamatsu Hospital Kazuyuki Hida Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center Shinichiro Ando Department of Internal Medicine Diabetic Center, Okayama City Hospital Hiroaki Akai Division of Diabetes and Metabolism, Faculty of Medicine, Tohoku Medical and Pharmaceutical University Yasushi Takahashi Department of Diabetes, Ochiai General Hospital Daisuke Koya Department of Diabetology and Endocrinology, Kanazawa Medical University Munehiro Kitada Department of Diabetology and Endocrinology, Kanazawa Medical University Hisashi Sugano Department of Diabetes and Endocrinology, Kochi Health Sciences Center Tomokazu Nunoue Nunoue Clinic Akihiko Nakamura Internal Medicine, Osafune Clinic, Setouchi Motofumi Sasaki Department of Diabetes and Endocrinology, Matsue City Hospital Tatsuaki Nakatou Diabetes Center, Okayama Saiseikai General Hospital Kei Fujimoto Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, The Jikei University Kashiwa Hospital Daiji Kawanami Department of Endocrinology and Diabetes Mellitus, Fukuoka University School of Medicine Takashi Wada Department of Nephrology and Laboratory Medicine, Graduate School of Medical Sciences, Kanazawa University Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Michihiro Yoshida Center for Innovative Clinical Medicine, Okayama University Hospital Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital the CANPIONE study Investigators Aim: To evaluate the effect of canagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, on albuminuria and the decline of estimated glomerular filtration rate (eGFR) in participants with type 2 diabetes and microalbuminuria.<br> Methods: The CANPIONE study is a multicentre, randomized, parallel-group and open-labelled study consisting of a unique 24-week preintervention period, during which the rate of eGFR decline before intervention is estimated, followed by a 52-week intervention and a 4-week washout period. Participants with a geometric mean urinary albumin-to-creatinine ratio (UACR) of 50 and higher and less than 300 mg/g in two consecutive first-morning voids at two different time points, and an eGFR of 45 ml/min/1.73m2 or higher, are randomly assigned to receive canagliflozin 100 mg daily or to continue guideline-recommended treatment, except for SGLT2 inhibitors. The first primary outcome is the change in UACR, and the second primary outcome is the change in eGFR slope.<br> Results: A total of 258 participants were screened and 98 were randomized at 21 sites in Japan from August 2018 to May 2021. The mean baseline age was 61.4 years and 25.8% were female. The mean HbA1c was 7.9%, mean eGFR was 74.1 ml/min/1.73m2 and median UACR was 104.2 mg/g.<br> Conclusions: The CANPIONE study will determine whether the SGLT2 inhibitor canagliflozin can reduce albuminuria and slow eGFR decline in participants with type 2 diabetes and microalbuminuria. No potential conflict of interest relevant to this article was reported.

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

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

The Editorial Office of Gut and Liver Acta Medica Okayama 1976-2283 17 3 2022 Postoperative Bleeding Risk after Gastric Endoscopic Submucosal Dissection in Patients Receiving a P2Y12 Receptor Antagonist 404 411 EN Ryosuke Hirai Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoko Inoo Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sakiko Kuraoka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shotaro Okanoue Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Satomi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenta Hamada Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiyasu Kono Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromitsu Kanzaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Aims: The safety of gastric endoscopic submucosal dissection (ESD) in users of a P2Y12 receptor antagonist (P2Y12RA) under current guidelines has not been verified.<br> Methods: Patients treated by gastric ESD at Okayama University Hospital between January 2013 and December 2020 were registered. The postoperative bleeding rates of patients (group A) who did not receive any antithrombotic drugs; patients (group B) receiving aspirin or cilostazol monotherapy; and P2Y12RA users (group C) those on including monotherapy or dual antiplatelet therapy were compared. The risk factors for post-ESD bleeding were examined in a multivariate analysis of patient background, tumor factors, and antithrombotic drug management.<br> Results: Ultimately, 1,036 lesions (847 patients) were enrolled. The bleeding rates of group B and C were significantly higher than that of group A (p=0.012 and p<0.001, respectively), but there was no significant difference between group B and C (p=0.11). The postoperative bleeding rate was significantly higher in dual antiplatelet therapy than in P2Y12RA monotherapy (p=0.014). In multivariate analysis, tumor diameter ≥12 mm (odds ratio [OR], 4.30; 95% confidence interval [CI], 1.99 to 9.31), anticoagulant use (OR, 4.03; 95% CI, 1.64 to 9.86), and P2Y12RA use (OR, 3.40; 95% CI, 1.07 to 10.70) were significant risk factors for postoperative bleeding.<br> Conclusions: P2Y12RA use is a risk factor for postoperative bleeding in patients who undergo ESD even if receiving drug management according to guidelines. Dual antiplatelet therapy carries a higher risk of bleeding than monotherapy. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 114 10 2023 Combination therapy with hydrogen peroxide and irradiation promotes an abscopal effect in mouse models 3848 3856 EN Naoya Kemmotsu Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Li Zhu 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 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 Yue Fang Department of Microbial and Biochemical Pharmacy, School of Pharmacy, China Medical 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 Hydrogen peroxide (H2O2) induces oxidative stress and cytotoxicity, and can be used for treating cancers in combination with radiotherapy. A product comprising H2O2 and sodium hyaluronate has been developed as a radiosensitizer. However, the effects of H2O2 on antitumor immunity remain unclear. To investigate the effects of H2O2, especially the abscopal effect when combined with radiotherapy (RT), we implanted murine tumor cells simultaneously in two locations in mouse models: the hind limb and back. H2O2 mixed with sodium hyaluronate was injected intratumorally, followed by irradiation only at the hind limb lesion. No treatment was administered to the back lesion. The H2O2/RT combination significantly reduced tumor growth at the noninjected/nonirradiated site in the back lesion, whereas H2O2 or RT individually did not reduce tumor growth. Flow cytometric analyses of the tumor-draining lymph nodes in the injected/irradiated areas showed that the number of dendritic cells increased significantly with maturation in the H2O2/RT combination group. In addition, analyses of tumor-infiltrating lymphocytes showed that the number of CD8+ (cluster of differentiation 8) T cells and the frequency of IFN-ƒΑ+ (interferon gamma) CD8+ T cells were higher in the noninjected/nonirradiated tumors in the H2O2/RT group compared to those in the other groups. PD-1 (programmed death receptor 1) blockade further increased the antitumor effect against noninjected/nonirradiated tumors in the H2O2/RT group. Intratumoral injection of H2O2 combined with RT therefore induces an abscopal effect by activating antitumor immunity, which can be further enhanced by PD-1 blockade. These findings promote the development of H2O2/RT therapy combined with cancer immunotherapies, even for advanced cancers. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2047-9980 12 10 2023 Significant Delayed Activation on the Right Ventricular Outflow Tract Represents Complete Right Bundle-Branch Block Pattern in Brugada Syndrome e028706 EN Yoshimasa Morimoto Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Hiroshi Morita Department of Cardiovascular Therapeutics , Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Tomofumi Mizuno Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Takuro Masuda Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Akira Ueoka Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Saori Asada Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Masakazu Miyamoto Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Satoshi Kawada Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Koji Nakagawa Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Nobuhiro Nishii Department of Cardiovascular Therapeutics , Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Hiroshi Ito Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Background: The appearance of complete right bundle-branch block (CRBBB) in Brugada syndrome (BrS) is associated with an increased risk of ventricular fibrillation. The pathophysiological mechanism of CRBBB in patients with BrS has not been well established. We aimed to clarify the significance of a conduction delay zone associated with arrhythmias on CRBBB using body surface mapping in patients with BrS. <br> Methods and Results: Body surface mapping was recorded in 11 patients with BrS and 8 control patients both with CRBBB. CRBBB in control patients was transiently exhibited by unintentional catheter manipulation (proximal RBBB). Ventricular activation time maps were constructed for both of the groups. We divided the anterior chest into 4 areas (inferolateral right ventricle [RV], RV outflow tract [RVOT], intraventricular septum, and left ventricle) and compared activation patterns between the 2 groups. Excitation propagated to the RV from the left ventricle through the intraventricular septum with activation delay in the entire RV in the control group (proximal RBBB pattern). In 7 patients with BrS, excitation propagated from the inferolateral RV to the RVOT with significant regional activation delay. The remaining 4 patients with BrS showed a proximal RBBB pattern with the RVOT activation delay. The ventricular activation time in the inferolateral RV was significantly shorter in patients with BrS without a proximal RBBB pattern than in control patients. <br> Conclusions: The CRBBB morphology in patients with BrS consisted of 2 mechanisms: (1) significantly delayed conduction in the RVOT and (2) proximal RBBB with RVOT conduction delay. Significant RVOT conduction delay without proximal RBBB resulted in CRBBB morphology in patients with BrS. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2042-0226 20 7 2023 The chemokine monocyte chemoattractant protein-1/CCL2 is a promoter of breast cancer metastasis 714 738 EN Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chunning Li Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuze Wang Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Breast cancer is the most prevalent cancer worldwide, and metastasis is the leading cause of death in cancer patients. Human monocyte chemoattractant protein-1 (MCP-1/CCL2) was isolated from the culture supernatants of not only mitogen-activated peripheral blood mononuclear leukocytes but also malignant glioma cells based on its in vitro chemotactic activity toward human monocytes. MCP-1 was subsequently found to be identical to a previously described tumor cell-derived chemotactic factor thought to be responsible for the accumulation of tumor-associated macrophages (TAMs), and it became a candidate target of clinical intervention; however, the role of TAMs in cancer development was still controversial at the time of the discovery of MCP-1. The in vivo role of MCP-1 in cancer progression was first evaluated by examining human cancer tissues, including breast cancers. Positive correlations between the level of MCP-1 production in tumors and the degree of TAM infiltration and cancer progression were established. The contribution of MCP-1 to the growth of primary tumors and metastasis to the lung, bone, and brain was examined in mouse breast cancer models. The results of these studies strongly suggested that MCP-1 is a promoter of breast cancer metastasis to the lung and brain but not bone. Potential mechanisms of MCP-1 production in the breast cancer microenvironment have also been reported. In the present manuscript, we review studies in which the role of MCP-1 in breast cancer development and progression and the mechanisms of its production were examined and attempt to draw a consensus and discuss the potential use of MCP-1 as a biomarker for diagnosis. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Research on Preparation of Aromatic Polyamide Hollow Spheres EN Hirofumi NAKAYAMA Graduate School of Environmental and Life Science, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Photochemical properties of carbon nanotube/dendrimer hybrids for photocatalytic H2 evolution from water and biomedical imaging EN Masahiro YAMAGAMI Graduate School of Environmental and Life Science, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Development of stereoselective constructions of ƒΐ-hydroxy-ƒΏ,ƒΏ-disubstituted ƒΏ-amino acid structures EN Yuya ARAKI Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Ž•ŽόŠ΄υE‰ŠΗ‚ͺ”DP‚βŽq‹{‘gD‚Ι‹y‚Ϊ‚·‰e‹Ώ‚Μ–Ζ‰uŠw“IŒŸ“’ EN Chiaki NAGATA 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 Emergency Dispatches for Suicide Attempts During the COVID-19 Outbreak in Okayama, Japan: A Descriptive Epidemiological Study EN Hiroshi HABU Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

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

Acta Medica Okayama 2023 Fabrication of scaffold-free mesenchyme tissue bands by cell self-aggregation technique for potential use in tissue regeneration EN Tomoyuki OTA 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 Involvement of a Basic Helix-Loop-Helix Gene BHLHE40 in Specification of Chicken Retinal Pigment Epithelium EN Toshiki KINUHATA 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 Upregulation of a nuclear factor-kappa B-interacting immune gene network in mice cochleae with age-related hearing loss EN Kensuke URAGUCHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

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

The Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 62 9 2023 Fulminant Myocarditis for Non-small-cell Carcinoma of the Lung with Nivolumab and Ipilimumab Plus Chemotherapy 1319 1322 EN Tomoka Nishimura Department of Allergy and Respiratory Medicine, Okayama University Hospital Kiichiro Ninomiya Department of Allergy and Respiratory Medicine, Okayama University Hospital Mitsutaka Nakashima Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadahiro Kuribayashi Department of Allergy and Respiratory Medicine, Okayama University Hospital Hisao Higo Department of Allergy and Respiratory Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital A 59-year-old man with a high level of antinuclear antibody received nivolumab and ipilimumab plus che-motherapy for lung cancer. Two weeks after the second course, he was admitted with a fever and severe fa-tigue. Laboratory studies showed elevated markers of myocardial damage, and a myocardial biopsy showed inflammatory cell infiltration, damaged myocardial fibers. Myocarditis was diagnosed as an immune-related adverse event (irAE), and high-dose corticosteroids were initiated. However, his cardiac function rapidly worsened, and he died on the fifth day after admission. There is no established treatment strategy for fulmi-nant myocarditis as an irAE, and the further exploration of viable treatment strategies is required. No potential conflict of interest relevant to this article was reported.

Oxford University Press Acta Medica Okayama 0449-3060 64 4 2023 Effects of low-dose/high-dose-rate X-irradiation on oxidative stress in organs following forced swim test and its combined effects on alcohol-induced liver damage in mice 635 643 EN Shota Naoe Graduate School of Health Sciences, Okayama University Yuki Fujimoto Graduate School of Health Sciences, Okayama University Kaito Murakami Graduate School of Health Sciences, Okayama University Ryohei Yukimine Graduate School of Health Sciences, Okayama University Ayumi Tanaka Graduate School of Health Sciences, Okayama University Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Takahiro Kataoka Faculty of Health Sciences, Okayama University The liver's susceptibility to oxidative stress after a combination of forced swim test (FST) and low-dose-rate gamma-irradiation has been observed. Therefore, this study aims to clarify the effects of low-dose (0.1 and 0.5 Gy)/high-dose-rate (1.2 Gy/min) irradiation on combined oxidative stressors-liver damage associated with FST and alcohol administration. In addition, the effects of similar irradiation on FST-induced immobility, which induces psychomotor retardation, and antioxidative effects on the brain, lungs, liver and kidneys were investigated, and the results were compared with those of a similar previous study that utilized low-dose-rate irradiation. Low-dose/high-dose-rate (especially 0.5 Gy) irradiation temporarily worsened liver antioxidant function and hepatic function with FST- and alcohol administration-related oxidative damage; however, the damages improved soon after. In addition, the increase in total glutathione content in the liver contributed to the early improvement of hepatic functions. However, pre-irradiation did not suppress immobility during the FST. The results also suggested that the effects of low-dose/high-dose-rate irradiation on the antioxidant functions of each organ after the FST were different from those of low-dose/low-dose-rate irradiation. Overall, this study provides further insights into the effects of low-dose irradiation on exposure to a combination of different oxidative stressors. It will also contribute to the elucidation of dose rate effects on oxidative stress in the low-dose irradiation range. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2047-9980 12 6 2023 Heat Exposure Following the Rainy Season Is Associated With an Increased Risk of Cardiovascular Emergency Among the Elderly in Japan e027046 EN Ryohei Fujimoto Department of Epidemiology, 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 Saori Kashima Environmental Health Sciences Laboratory, Graduate School of Advanced Science and Engineering, Hiroshima University Kazufumi Nakamura Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiroshi Ito Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Despite the impact of heat exposure caused by global warming, few studies have investigated the hourly effects of heat exposure and the risk of cardiovascular disease (CVD) in the elderly. We examined the associations between short-term heat exposure and the risk of CVD in the elderly in Japan and evaluated possible effect-measure modifications by rainy seasons that occur in East Asia. <br> Methods and Results: We conducted a time-stratified case-crossover study. The study included 6527 residents in Okayama City, Japan, aged >= 65 years who were transported to emergency hospitals between 2012 and 2019 for the onset of CVD during and a few months after the rainy seasons. We examined the linear associations between temperature and CVD-related emergency calls for each year and for hourly preceding intervals before the emergency call during the most relevant months. Heat exposure during 1 month after the end of the rainy season was associated with CVD risk; the odds ratio (OR) for a 1 degrees C increase in temperature was 1.34 (95% CI, 1.29-1.40). When we further explored the nonlinear association by using the natural cubic spline model, we found a J-shaped relationship. Exposures 0 to 6 hours before the case event (preceding intervals 0-6 hours) were associated with CVD risk, particularly for the preceding interval 0 to 1 hour (OR, 1.33 [95% CI, 1.28-1.39]). For longer periods, the highest risk was at preceding intervals 0 to 23 hours (OR, 1.40 [95% CI, 1.34-1.46]).<br> Conclusions: Elderly individuals may be more susceptible to CVD after heat exposure during the month after the rainy season. As shown by finer temporal resolution analyses, short-term exposure to increasing temperature can trigger CVD onset. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0949-2658 28 5 2023 The stability of repaired meniscal root can affect postoperative cartilage status following medial meniscus posterior root repair 1060 1067 EN Ximing Zhang Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Takaaki Hiranaka Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Yuki Okazaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Haowei Xue Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Keisuke Kintaka Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Shinichi Miyazawa Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Background<br> Transtibial pullout repair yields beneficial clinical outcomes in patients with medial meniscus (MM) posterior root tear. However, the relationship between repaired meniscal root healing status and postoperative clinical outcomes remains unclear. We aimed to evaluate changes in articular cartilage damage and clinical scores after pullout repair using two simple stitches (TSS).<br> <br> Methods<br> Thirty-three patients who underwent pullout repair using TSS were assessed. Healing status was assessed by a semi-quantitative second-look arthroscopic scoring system comprising three evaluation criteria (width of bridging tissues, stability of the repaired root, and synovial coverage), 1 year postoperatively. MM medial extrusion (MMME) and cartilage damage were assessed preoperatively and 1 year postoperatively. The medial compartment was divided into 8 zones (A-H) for comparison of preoperative and 1-year postoperative cartilage damage. Clinical outcomes were evaluated using the Knee Injury and Osteoarthritis Outcome score, Lysholm score, International Knee Documentation Committee scores, and visual analogue scale pain score.<br> <br> Results<br> Although cartilage damage did not aggravate significantly in most medial compartment areas, MMME progressed at 1 year postoperatively. No statistical differences were observed in cartilage damage between the central-to-medial area of the medial femoral condyle and the medial tibial plateau area at 1 year postoperatively. Regarding semi-quantitative healing scores, the stability score was significantly correlated with the International Cartilage Repair Society grade at 1 year postoperatively. All 1-year and 2-year clinical scores significantly improved compared with the preoperative scores.<br> <br> Conclusion<br> Regarding TSS repair, stability of repaired meniscal root negatively correlated with cartilage damage in the medial compartment loading area. All 1-year and 2-year clinical scores significantly improved than those of the preoperative scores. Achieving MM stability is crucial for suppressing cartilage degeneration.<br> <br> Level of evidence<br> IV case series study. No potential conflict of interest relevant to this article was reported.

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

Oxford University Press Acta Medica Okayama 2050-3911 2023 1 2023 Detection of the 4.4-MeV gamma rays from 16O(ƒΛ, ƒΛŒ)16O(12.97 MeV, 2|) with a water Cherenkov detector in supernova neutrino bursts 013D02 EN Makoto Sakuda Physics Department, Okayama University Toshio Suzuki Department of Physics, College of Humanities and Sciences, Nihon University Mandeep Singh Reen Department of Physics, Akal University Ken'Ichiro Nakazato Faculty of Arts and Science, Kyushu University Hideyuki Suzuki Department of Physics, Faculty of Science and Technology, Tokyo University of Science We first discuss and determine the isospin mixing of the two 2| states (12.53 MeV and 12.97 MeV) of the16O nucleus using inelastic electron scattering data. We then evaluate the cross section of 4.4-MeV ƒΑ rays produced in the neutrino neutral-current (NC) reaction 16O(ƒΛ, ƒΛŒ)16O(12.97 MeV, 2|) in a water Cherenkov detector at a low energy, below 100 MeV. The detection of ƒΑ rays for EƒΑ > 5 MeV from the NC reaction 16O(ƒΛ, ƒΛŒ)16O(Ex > 16 MeV, T = 1) with a water Cherenkov detector in supernova neutrino bursts has been proposed and discussed by several authors previously. In this article, we discuss a new NC reaction channel from 16O(12.97 MeV, 2|) producing a 4.4-MeV ƒΑ ray, the cross section of which is more robust and even larger at low energy (EƒΛ < 25 MeV) than the NC cross section from 16O(Ex > 16 MeV, T = 1). We also evaluate the number of such events induced by neutrinos from supernova explosion which can be observed by the Super-Kamiokande, an Earth-based 32-kton water Cherenkov detector. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 24 5 2023 SPRED2: A Novel Regulator of Epithelial-Mesenchymal Transition and Stemness in Hepatocellular Carcinoma Cells 4996 EN Tong Gao Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xu Yang Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tianyi Wang Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nahoko Tomonobu Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masakiyo Sakaguchi Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The downregulation of SPRED2, a negative regulator of the ERK1/2 pathway, was previously detected in human cancers; however, the biological consequence remains unknown. Here, we investigated the effects of SPRED2 loss on hepatocellular carcinoma (HCC) cell function. Human HCC cell lines, expressing various levels of SPRED2 and SPRED2 knockdown, increased ERK1/2 activation. SPRED2-knockout (KO)-HepG2 cells displayed an elongated spindle shape with increased cell migration/invasion and cadherin switching, with features of epithelial-mesenchymal transition (EMT). SPRED2-KO cells demonstrated a higher ability to form spheres and colonies, expressed higher levels of stemness markers and were more resistant to cisplatin. Interestingly, SPRED2-KO cells also expressed higher levels of the stem cell surface markers CD44 and CD90. When CD44(+)CD90(+) and CD44(-)CD90(-) populations from WT cells were analyzed, a lower level of SPRED2 and higher levels of stem cell markers were detected in CD44(+)CD90(+) cells. Further, endogenous SPRED2 expression decreased when WT cells were cultured in 3D, but was restored in 2D culture. Finally, the levels of SPRED2 in clinical HCC tissues were significantly lower than those in adjacent non-HCC tissues and were negatively associated with progression-free survival. Thus, the downregulation of SPRED2 in HCC promotes EMT and stemness through the activation of the ERK1/2 pathway, and leads to more malignant phenotypes. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0022-5223 166 3 2023 When to Intervene the Pulmonary Artery: Importance of Anatomical Assessment in the Diagnosis of Pulmonary Artery Coarctation 926 932 EN Eiri Kisamori Department of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University Hospital Yasuhiro Kotani Department of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University Hospital Hiroyuki Suzuki Department of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University Hospital Junko Kobayashi Department of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University Hospital Takuya Kawabata Department of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University Hospital Yosuke Kuroko Department of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University Hospital Shingo Kasahara Department of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University Hospital Objective: Pulmonary artery coarctation (PACoA) is a major problem that increases the frequency of intervention. However, there is little evidence regarding the prediction of PACoA development.<br> Methods: A retrospective chart review was performed on 42 patients who underwent modified Blalock-Taussig shunt and preoperative contrast-enhanced computed tomography. An uneven PA branching was defined as an abnormal ductus arteriosus connection to the left PA distal to the PA branching on contrast-enhanced computed tomography.<br> Results: Nineteen (45.2%) of 42 patients were diagnosed with PACoA. The median diameters of the ductus on the aorta and PA sides were 4.1 mm and 3.6 mm in the PACoA group and 3.6 mm and 2.9 mm in the non-PACoA group, respectively (P = .07 and .28, respectively). Tortuous ductus was recognized in 7 (36.8%) patients in the PACoA group and 14 (60.8%) patients in the non-PACoA group (P = .12). PACoA was associated with pulmonary atresia (16 patients [84.2%] in the PACoA group and 12 patients [52.1%] in the non-PACoA group) (P = .02). All 19 patients had uneven PA branching in the PACoA group, whereas 5 of 23 (21.7%) patients had uneven PA branching in the non-PACoA group (P < .001).<br> Conclusions: Uneven PA branching rather than the ductus arteriosus size was strongly associated with PACoA development; therefore, morphologic assessment by contrast-enhanced computed tomography should be considered in patients with pulmonary atresia. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 13695266 69 2022 Polyploidy before and after domestication of crop species 102255 EN Takashi Akagi Graduate School of Environmental and Life Science, Okayama University Katharina Jung Department of Evolutionary Biology and Environmental Studies, University of Zurich Kanae Masuda Graduate School of Environmental and Life Science, Okayama University Kentaro K. Shimizu Department of Evolutionary Biology and Environmental Studies, University of Zurich Recent advances in the genomics of polyploid species answer some of the long-standing questions about the role of polyploidy in crop species. Here, we summarize the current literature to reexamine scenarios in which polyploidy played a role both before and after domestication. The prevalence of polyploidy can help to explain environmental robustness in agroecosystems. This review also clarifies the molecular basis of some agriculturally advantageous traits of polyploid crops, including yield increments in polyploid cotton via subfunctionalization, modification of a separated sexuality to selfing in polyploid persimmon via neofunctionalization, and transition to a selfing system via nonfunctionalization combined with epistatic interaction between duplicated S-loci. The rapid progress in genomics and genetics is discussed along with how this will facilitate functional studies of understudied polyploid crop species. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6643 15 3 2023 Association between Cardiovascular Disease and Liver Disease, from a Clinically Pragmatic Perspective as a Cardiologist 748 EN Mitsutaka Nakashima Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazufumi Nakamura Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takahiro Nishihara Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keishi Ichikawa Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Rie Nakayama Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoichi Takaya Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Norihisa Toh Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Akagi Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Miyoshi Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teiji Akagi Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Ito Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Cardiovascular diseases and liver diseases are closely related. Non-alcoholic fatty liver disease has the same risk factors as those for atherosclerotic cardiovascular disease and may also be a risk factor for atherosclerotic cardiovascular disease on its own. Heart failure causes liver fibrosis, and liver fibrosis results in worsened cardiac preload and congestion. Although some previous reports regard the association between cardiovascular diseases and liver disease, the management strategy for liver disease in patients with cardiovascular diseases is not still established. This review summarized the association between cardiovascular diseases and liver disease. In patients with non-alcoholic fatty liver disease, the degree of liver fibrosis progresses with worsening cardiovascular prognosis. In patients with heart failure, liver fibrosis could be a prognostic marker. Liver stiffness assessed with shear wave elastography, the fibrosis-4 index, and non-alcoholic fatty liver disease fibrosis score is associated with both liver fibrosis in patients with liver diseases and worse prognosis in patients with heart failure. With the current population ageing, the importance of management for cardiovascular diseases and liver disease has been increasing. However, whether management and interventions for liver disease improve the prognosis of cardiovascular diseases has not been fully understood. Future investigations are needed. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 Analysis of Phase Angle and Balance and Gait Functions in Pre-Frail Individuals: A Cross-Sectional Observational Study 21 27 EN Daisuke Homma Orthopaedic Surgery, Niigata University Graduate School of Medical and Dental Sciences Izumi Minato Division of Orthopaedic Surgery, Niigata Rinko Hospital Norio Imai Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences Dai Miyasaka Division of Orthopaedic Surgery, Niigata Bandai Hospital Yoshinori Sakai Division of Orthopaedic Surgery, Niigata City General Hospital Yoji Horigome Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences Hayato Suzuki Orthopaedic Surgery, Niigata University Graduate School of Medical and Dental Sciences Yoichiro Dohmae Division of Orthopaedic Surgery, Niigata Bandai Hospital Naoto Endo Division of Orthopaedic Surgery, Niigata Prefectural Tsubame Rosai Hospital Original Article 10.18926/AMO/64357 We measured the muscle mass and phase angle of each body part to evaluate the relationship between balance and gait functions in individuals with a pre-frailty status. This cross-sectional observational study determined the skeletal muscle mass-to-body weight ratio and phase angles of 21 control (robust) and 29 pre-frail subjects. Their Brief-Balance Evaluation Systems Test, Timed Up-and-Go (TUG) test, Life-Space Assessment, and Modified Fall Efficacy Scale scores plus the relationship between muscle mass, phase angle, and motor function were evaluated. In the pre-frailty group (three males, 26 females, aged 75.58}7.60 years), significant correlations were noted between the Brief-Balance Evaluation Systems Test score and lower-limb (r=0.614) and wholebody (r=0.557) phase angles, and between the TUG test score and lower-limb muscle mass-to-body weight ratio (r=|0.616), lower-limb phase angle (r=|0.616), and whole-body phase angle (r=|0.527). Evaluating the phase angle of the lower extremities of pre-frail patients and intervening accordingly may help clinicians maintain and improve these patientsf balance and gait functions. No potential conflict of interest relevant to this article was reported.

‰ͺŽR‘εŠwŽ‘ŒΉA•¨‰ΘŠwŒ€‹†Š Acta Medica Okayama 2186-4918 30 2023 ‰ͺŽR‘εŠwŽ‘ŒΉA•¨‰ΘŠwŒ€‹†Š•ρ 1 68 EN Institute of Plant Science and Resources, Okayama University No potential conflict of interest relevant to this article was reported.

‰ͺŽR‘εŠw”_Šw•” Acta Medica Okayama 2186-7755 112 2023 Comparison of LEDs, Fluorescent Lamps and Incandescent Bulbs for Long-day Treatment of Forcing Strawberries as Affected by Respective Color Temperature 1 6 EN Yuichi Yoshida Graduate School of Environmental and Life Science, Okayama University Atsushi Hanada Graduate School of Environmental and Life Science, Okayama University Keita Ooguma Faculty of Agriculture, Okayama University Kenta Yoshida Japan Agency for Marine-Earth Science and Technology Tanjuro Goto Graduate School of Environmental and Life Science, Okayama University Yoshiyuki Tanaka Graduate School of Agriculture, Kyoto University Ken-ichiro Yasuba Graduate School of Environmental and Life Science, Okayama University Long day (LD) treatment is frequently applied for horticultural crops, including strawberry, and sufficient effect similar to 4 to 6hours of day time elongation in the evening can be achieved by 1 to 3hours of night break in the mid night. Incandescent lamps (IC) have long been an important light source, but the general incandescent lamps are out of production and have been replaced with LED or florescent lamps (FL). Thus, we compared light sources and their color temperature (2,800K, warm white similar to IC; 6,500K, daylight) in different lighting programs. The effectiveness of 3 and 4cycles of alternate intermittent lighting, 30min on/30min off, were equal to and larger than 2hours of night break, respectively. Measured intensity of illumination (lux) at the canopy surface by 2,800K LED (6.9W) and FL (12W) was 1.50 and 0.95times as large as IC (54W), but leaf growth under LED and FL was similar to and less vigorous than IC, respectively. On the other hand, intensity values of illumination by 6,500K LED (6.9W) and FL (12W) were both 1.20times as large as 2,800K ones, but 6,500K light sources were much less effective compared to 2,800K ones. Daylight type LED and FL which have higher luminance efficiency but emit less red light compared to warm white ones, are not suitable as alternative light sources for IC. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2079-7737 12 1 2023 Extracellular Vesicles: New Classification and Tumor Immunosuppression 110 EN Mona Sheta Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eman A. Taha Department of Biochemistry, Faculty of Science, Ain Shams University Yanyin Lu Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takanori Eguchi Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Simple Summary Extracellular vesicles (EVs) are cell-derived membrane-surrounded vesicles that carry bioactive molecules and deliver them to recipient cells. Classical EVs are exosomes, microvesicles, and apoptotic bodies. This review classifies classical and additional EV types, including autophagic EVs, matrix vesicles, and stressed EVs. Of note, matrix vesicles are key components interacting with extracellular matrices (ECM) in the tumor microenvironment. We also review how EVs are involved in the communication between cancer cells and tumor-associated cells (TAC), leading to establishing immunosuppressive and chemoresistant microenvironments. These include cancer-associated fibroblasts (CAF), mesenchymal stem cells (MSC), blood endothelial cells (BEC), lymph endothelial cells (LEC), and immune cells, such as tumor-associated macrophages (TAM), tumor-associated neutrophils (TAN), dendritic cells, natural killer cells, killer T cells, and immunosuppressive cells, such as regulatory T cells and myeloid-derived suppressor cells (MDSC). Exosomal long noncoding RNA (lncRNA), microRNA, circular RNA, piRNA, mRNA, and proteins are crucial in communication between cancer cells and TACs for establishing cold tumors. Extracellular vesicles (EVs) are cell-derived membrane-surrounded vesicles carrying various types of molecules. These EV cargoes are often used as pathophysiological biomarkers and delivered to recipient cells whose fates are often altered in local and distant tissues. Classical EVs are exosomes, microvesicles, and apoptotic bodies, while recent studies discovered autophagic EVs, stressed EVs, and matrix vesicles. Here, we classify classical and new EVs and non-EV nanoparticles. We also review EVs-mediated intercellular communication between cancer cells and various types of tumor-associated cells, such as cancer-associated fibroblasts, adipocytes, blood vessels, lymphatic vessels, and immune cells. Of note, cancer EVs play crucial roles in immunosuppression, immune evasion, and immunotherapy resistance. Thus, cancer EVs change hot tumors into cold ones. Moreover, cancer EVs affect nonimmune cells to promote cellular transformation, including epithelial-to-mesenchymal transition (EMT), chemoresistance, tumor matrix production, destruction of biological barriers, angiogenesis, lymphangiogenesis, and metastatic niche formation. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 24 1 2023 Cycloartenyl Ferulate Is the Predominant Compound in Brown Rice Conferring Cytoprotective Potential against Oxidative Stress-Induced Cytotoxicity 822 EN Hongyan Wu School of Food Science and Technology, Dalian Polytechnic University Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University Yingnan Guo School of Food Science and Technology, Dalian Polytechnic University Riho Matsumoto Graduate School of Environmental and Life Science, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Since brown rice extract is a rich source of biologically active compounds, the present study is aimed to quantify the major compounds in brown rice and to compare their cytoprotective potential against oxidative stress. The content of the main hydrophobic compounds in brown rice followed the order of cycloartenyl ferulate (CAF) (89.00 +/- 8.07 nmol/g) >> alpha-tocopherol (alpha T) (19.73 +/- 2.28 nmol/g) > gamma-tocotrienol (gamma T3) (18.24 +/- 1.41 nmol/g) > alpha-tocotrienol (alpha T3) (16.02 +/- 1.29 nmol/g) > gamma-tocopherol (gamma T) (3.81 +/- 0.40 nmol/g). However, the percent contribution of CAF to the radical scavenging activity of one gram of whole brown rice was similar to those of alpha T, alpha T3, and gamma T3 because of its weaker antioxidant activity. The CAF pretreatment displayed a significant cytoprotective effect on the hydrogen peroxide-induced cytotoxicity from 10 mu M, which is lower than the minimal concentrations of alpha T and gamma T required for a significant protection. CAF also enhanced the nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation coincided with the enhancement of the heme oxygenase-1 (HO-1) mRNA level. An HO-1 inhibitor, tin protoporphyrin IX (SnPP), significantly impaired the cytoprotection of CAF. The cytoprotective potential of CAF is attributable to its cycloartenyl moiety besides the ferulyl moiety. These results suggested that CAF is the predominant cytoprotector in brown rice against hydrogen peroxide-induced cytotoxicity. No potential conflict of interest relevant to this article was reported.

Taylor & Francis Ltd Acta Medica Okayama 1742-9145 18 1 2023 Identification of quantitative trait loci associated with sorghum susceptibility to Asian stem borer damage 2153182 EN Cyprian Osinde Institute of Plant Science and Resources, Okayama University Wataru Sakamoto Institute of Plant Science and Resources, Okayama University Hiromi Kajiya-Kanegae Graduate School of Agricultural and Life Sciences, The University of Tokyo Islam S. Sobhy Institute of Plant Science and Resources, Okayama University Arthur K. Tugume Department of Plant Science, Microbiology and Biotechnology Makerere University Anthony M. Nsubuga Department of Plant Science, Microbiology and Biotechnology Makerere University Ivan Galis Institute of Plant Science and Resources, Okayama University Sorghum (Sorghum bicolor (L.) Moench) is an important crop originated in Africa that shows susceptibility to herbivores. In this study, we identified two sorghum genotypes with highly contrasting levels of stem damage caused by the caterpillars of Asian stem borer (Ostrinia furnacalis Guenee). Recombinant inbred lines (RILs) from genetic cross between resistant (BTx623) and susceptible (NOG) sorghum were used to perform a quantitative trait locus (QTL) analysis in the field. Two major QTLs responsible for higher NOG infestation by stem borer in three independent field seasons were detected on chromosomes 7 and 9, interestingly in positions that overlapped with two major QTLs for plant height. As plant height and stem borer damage were highly correlated, we propose that sorghum height-associated morphological or physiological traits could be important for stem borer establishment and/or damage in sorghum. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2221-3759 10 4 2022 Involvement of a Basic Helix-Loop-Helix Gene BHLHE40 in Specification of Chicken Retinal Pigment Epithelium 45 EN Toshiki Kinuhata Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keita Sato Department of Cytology and Histology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Bando Department of Cytology and Histology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Taro Mito Bio-Innovation Research Center, Tokushima University Satoru Miyaishi Department of Legal Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Tsutomu Nohno Department of Cytology and Histology, Okayama University Medical School Hideyo Ohuchi Department of Cytology and Histology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences The first event of differentiation and morphogenesis in the optic vesicle (OV) is specification of the neural retina (NR) and retinal pigment epithelium (RPE), separating the inner and outer layers of the optic cup, respectively. Here, we focus on a basic helix-loop-helix gene, BHLHE40, which has been shown to be expressed by the developing RPE in mice and zebrafish. Firstly, we examined the expression pattern of BHLHE40 in the developing chicken eye primordia by in situ hybridization. Secondly, BHLHE40 overexpression was performed with in ovo electroporation and its effects on optic cup morphology and expression of NR and RPE marker genes were examined. Thirdly, we examined the expression pattern of BHLHE40 in LHX1-overexpressed optic cup. BHLHE40 expression emerged in a subset of cells of the OV at Hamburger and Hamilton stage 14 and became confined to the outer layer of the OV and the ciliary marginal zone of the retina by stage 17. BHLHE40 overexpression in the prospective NR resulted in ectopic induction of OTX2 and repression of VSX2. Conversely, BHLHE40 was repressed in the second NR after LHX1 overexpression. These results suggest that emergence of BHLHE40 expression in the OV is involved in initial RPE specification and that BHLHE40 plays a role in separation of the early OV domains by maintaining OTX2 expression and antagonizing an NR developmental program. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6694 14 24 2022 The Effect of Pleural Effusion on Prognosis in Patients with Non-Small Cell Lung Cancer Undergoing Immunochemotherapy: A Retrospective Observational Study 6184 EN Tomoka Nishimura Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Toshihide Yokoyama Department of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital Koji Inoue Department of Respiratory Medicine, Ehime Prefectural Central Hospital Tomoki Tamura Department of Respiratory Medicine, NHO Iwakuni Clinical Center Ken Sato Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center Naohiro Oda Department of Internal Medicine, Fukuyama City Hospital Hirohisa Kano Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Daizo Kishino Department of Respiratory Medicine, Japanese Red Cross Society Himeji Hospital Haruyuki Kawai Department of Internal Medicine, Okayama Saiseikai General Hospital Masaaki Inoue Department of Chest Surgery, Shimonoseki City Hospital Nobuaki Ochi Department of General Internal Medicine 4, Kawasaki Medical School Nobukazu Fujimoto Department of Respiratory Medicine, Okayama Rosai Hospital Hirohisa Ichikawa Department of Respiratory Medicine, KKR Takamatsu Hospital Chihiro Ando Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Simple Summary Minimal data exists on pleural effusion (PE) for non-small cell lung cancer (NSCLC) patients undergoing combined ICI and chemotherapy. We retrospectively investigated how PE affects survival outcomes in patients with NSCLC undergoing this combined therapy. We identified 478 patients who underwent combined ICI therapy and chemotherapy; 357 patients did not have PE, and 121 patients did have PE. Patients with PE had significantly shorter progression-free survival and overall survival than those without PE. In addition, bevacizumab-containing regimens did not improve the survival outcomes for patients with PE. In conclusion, PE was associated with poor outcomes among patients with NSCLC undergoing combined ICI therapy and chemotherapy. Objectives: Combined immune checkpoint inhibitor (ICI) therapy and chemotherapy has become the standard treatment for advanced non-small-cell lung cancer (NSCLC). Pleural effusion (PE) is associated with poor outcomes among patients with NSCLC undergoing chemotherapy. However, minimal data exists on PE for patients undergoing combined ICI and chemotherapy. Therefore, we investigated how PE affects survival outcomes in patients with NSCLC undergoing this combined therapy. Methods: We identified patients with advanced NSCLC undergoing chemotherapy and ICI therapy from the Okayama Lung Cancer Study Group-Immune Chemotherapy Database (OLCSG-ICD) between December 2018 and December 2020; the OLCSG-ICD includes the clinical data of patients with advanced NSCLC from 13 institutions. Then, we analyzed the treatment outcomes based on the presence of PE. Results: We identified 478 patients who underwent combined ICI therapy and chemotherapy; 357 patients did not have PE, and 121 patients did have PE. Patients with PE had significantly shorter progression-free survival (PFS) and overall survival (OS) than those without PE (median PFS: 6.2 months versus 9.1 months; p < 0.001; median OS: 16.4 months versus 27.7 months; p < 0.001). The negative effect of PE differed based on the patient's programmed cell death-ligand 1 (PD-L1) expression status; with the effect being more evident in patients with high PD-L1 expression. In addition, PFS and OS did not differ between patients who did and did not undergo bevacizumab treatment; thus, bevacizumab-containing regimens did not improve the survival outcomes for patients with PE. Conclusion: PE is associated with poor outcomes among patients with NSCLC undergoing combined ICI therapy and chemotherapy. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1424-8220 22 22 2022 A Throughput Request Satisfaction Method for Concurrently Communicating Multiple Hosts in Wireless Local Area Network 8823 EN Md Mahbubur Rahman Graduate School of Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Natural Science and Technology, Okayama University Kwenga Ismael Munene Graduate School of Natural Science and Technology, Okayama University Sujan Chandra Roy Graduate School of Natural Science and Technology, Okayama University Minoru Kuribayashi Graduate School of Natural Science and Technology, Okayama University Melki Mario Gulo Department of Informatics and Computer Engineering, Politeknik Elektronika Negeri Surabaya Wen-Chung Kao Department of Electrical Engineering, National Taiwan Normal University Nowadays, the IEEE 802.11 wireless local area network (WLAN) has been widely used for Internet access services around the world. Then, the unfairness or insufficiency in meeting the throughput request can appear among concurrently communicating hosts with the same access point (AP), which should be solved by sacrificing advantageous hosts. Previously, we studied the fairness control method by adopting packet transmission delay at the AP. However, it suffers from slow convergence and may not satisfy different throughput requests among hosts. In this paper, we propose a throughput request satisfaction method for providing fair or different throughput requests when multiple hosts are concurrently communicating with a single AP. To meet the throughput request, the method (1) measures the single and concurrent throughput for each host, (2) calculates the channel occupying time from them, (3) derives the target throughput to achieve the given throughput request, and (4) controls the traffic by applying traffic shaping at the AP. For evaluations, we implemented the proposal in the WLAN testbed system with one Raspberry Pi AP and up to five hosts, and conducted extensive experiments in five scenarios with different throughput requests. The results confirmed the effectiveness of our proposal. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1010-660X 58 11 2022 The Beneficial Effect of Personalized Lifestyle Intervention in Chronic Kidney Disease Follow-Up Project for National Health Insurance Specific Health Checkup: A Five-Year Community-Based Cohort Study 1529 EN Hidemi Takeuchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Science Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Science Katsuyoshi Katayama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Science Natsumi Matsuoka-Uchiyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Science Shugo Okamoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Science Yasuhiro Onishi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Science Yuka Okuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Science Ryoko Umebayashi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Science Kodai Miyaji Department of Health and Welfare, Division of Health Promotion, Mimasaka City Health Center Akiko Kai Department of Health and Welfare, Division of Health Promotion, Mimasaka City Health Center Izumi Matsumoto Department of Health and Welfare, Division of Health Promotion, Mimasaka City Health Center Keiko Taniguchi Department of Health and Welfare, Division of Health Promotion, Mimasaka City Health Center Fukiko Yamashita Department of Health and Welfare, Division of Health Promotion, Mimasaka City Health Center Tsutomu Emi Department of Health and Welfare, Division of Health Promotion, Mimasaka City Health Center Hitoshi Sugiyama Kawasaki Medical School General Medical Center Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Science Background and Objectives: Mimasaka city is a relatively small city with a population of 28,381, and an aging rate (>= 65 years old) of 38.9%, where only one nephrology clinic is available. Since 2013, the city has conducted its own unique lifestyle intervention for the participants of the National Health Insurance specific medical health checkup, aiming to prevent the progression of chronic kidney disease (CKD) severity. Materials and Methods: The persons in National Health Insurance specific medical health checkup (40-74 years old) conducted in Mimasaka city in 2013, with eGFR less than 50 mL/min/1.73 m(2) or 50-90 mL/min/1.73 m(2) with urine dipstick protein 1+ or more, were registered for the CKD follow-up project, as high-risk subjects for advanced renal dysfunction. Municipal workers directly visited the subjects' homes to provide individual health guidance and encourage medical consultation. We aimed to examine the effect of home-visit intervention on the changes of renal function and related factors until 2017. Results: The number of the high-risk subjects who continuously received the health checkup until 2017 was 63, and only 23 (36.5%) visited a medical institution in the first year. The eGFR decreased by only 0.4 mL/min/1.73 m(2)/year, and the subjects with urinary protein 1+ or higher decreased significantly from 20 (31.7%) to 9 (14.3%) (p = 0.034) in the high-risk subjects. The changes in eGFR and urinary protein was almost in the same fashion regardless of their medical institution visits. Next, we examined the effects of various factors on Delta eGFR, the changes of eGFR from 2013 to 2017, by multivariate linear regression analysis. The effects of medical institution visit were not significant, and the degree of urinary protein (coefficient B: 4.503, beta: 0.705, p < 0.001), age (coefficient B: 4.753, beta: 0.341, p = 0.004), and smoking (coefficient B: 5.878, beta: 0.295, p = 0.031) had independent significant effects, indicating that they were the factors exacerbating the decrease in eGFR from the baseline. Conclusions: The personalized lifestyle intervention by home-visit in CKD follow-up project showed the possibility of beneficial effects on the deterioration of renal function. This may be an efficient method to change behavior in a small community with limited medical resources. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Molecular characterization of quantitative trait loci controlling element accumulation in sorghum grains EN FIONA WACERA WAHINYA Graduate School of Environmental and Life Science, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 A Study of Throughput Control Method for Concurrently Communicating Multiple Hosts in Wireless Local-Area Network EN MD. MAHBUBUR RAHMAN Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

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

MDPI Acta Medica Okayama 1422-0067 23 19 2022 Molecular Mechanisms Underlying Ca2+/Calmodulin-Dependent Protein Kinase Kinase Signal Transduction 11025 EN Hiroshi Tokumitsu 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 Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) is the activating kinase for multiple downstream kinases, including CaM-kinase I (CaMKI), CaM-kinase IV (CaMKIV), protein kinase B (PKB/Akt), and 5'AMP-kinase (AMPK), through the phosphorylation of their activation-loop Thr residues in response to increasing the intracellular Ca2+ concentration, as CaMKK itself is a Ca2+/CaM-dependent enzyme. The CaMKK-mediated kinase cascade plays important roles in a number of Ca2+-dependent pathways, such as neuronal morphogenesis and plasticity, transcriptional activation, autophagy, and metabolic regulation, as well as in pathophysiological pathways, including cancer progression, metabolic syndrome, and mental disorders. This review focuses on the molecular mechanism underlying CaMKK-mediated signal transduction in normal and pathophysiological conditions. We summarize the current knowledge of the structural, functional, and physiological properties of the regulatory kinase, CaMKK, and the development and application of its pharmacological inhibitors. No potential conflict of interest relevant to this article was reported.

Institute of Electronics, Information and Communications Engineers (IEICE) Acta Medica Okayama 0916-8516 E105.B 9 2022 Asynchronous Periodic Interference Signals Cancellation in Frequency Domain 1087 1096 EN Satoshi DENNO Graduate School of Natural Science and Technology, Okayama University Yafei HOU Graduate School of Natural Science and Technology, Okayama University This paper proposes a novel interference cancellation technique that prevents radio receivers from degrading due to periodic interference signals caused by electromagnetic waves emitted from high power circuits. The proposed technique cancels periodic interference signals in the frequency domain, even if the periodic interference signals drift in the time domain. We propose a drift estimation based on a super resolution technique such as ESPRIT. Moreover, we propose a sequential drift estimation to enhance the drift estimation performance. The proposed technique employs a linear filter based on the minimum mean square error criterion with assistance of the estimated drifts for the interference cancellation. The performance of the proposed technique is confirmed by computer simulation. The proposed technique achieves a gain of more than 40dB at the higher frequency part in the band. The proposed canceler achieves such superior performance, if the parameter sets are carefully selected. The proposed sequential drift estimation relaxes the parameter constraints, and enables the proposed cancellation to achieve the performance upper bound. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1660-4601 19 17 2022 Immunomodulatory Effects of Radon Inhalation on Lipopolysaccharide-Induced Inflammation in Mice 10632 EN Takahiro Kataoka Faculty of Health Sciences, Okayama University Shota Naoe Graduate School of Health Sciences, Okayama University Kaito Murakami Graduate School of Health Sciences, Okayama University Yuki Fujimoto Graduate School of Health Sciences, Okayama University Ryohei Yukimine Graduate School of Health Sciences, Okayama University Ayumi Tanaka Graduate School of Health Sciences, Okayama University Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Typical indications for radon therapy include autoimmune diseases such as rheumatoid arthritis (RA). We had previously reported that radon inhalation inhibits Th17 immune responses in RA mice by activating Th1 and Th2 immune responses. However, there are no reports on how radon inhalation affects the activated Th1 and Th17 immune responses, and these findings may be useful for identifying new indications for radon therapy. Therefore, in this study, we investigated the effect of radon inhalation on the lipopolysaccharide (LPS)-induced inflammatory response, focusing on the expression of related cytokines and antioxidant function. Male BALB/c mice were exposed to 2000 Bq/m(3) radon for one day. Immediately after radon inhalation, LPS was administered intraperitoneally at 1.0 mg/kg body weight for 4 h. LPS administration increased the levels of Th1- and Th17-prone cytokines, such as interleukin-2, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor, compared to no treatment control (sham). However, these effects were suppressed by radon inhalation. IL-10 levels were significantly increased by LPS administration, with or without radon inhalation, compared to sham. However, radon inhalation did not inhibit oxidative stress induced by LPS administration. These findings suggest that radon inhalation has immunomodulatory but not antioxidative functions in LPS-induced injury. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9067 9 8 2022 Novel Lung Growth Strategy with Biological Therapy Targeting Airway Remodeling in Childhood Bronchial Asthma 1253 EN Mitsuru Tsuge Department of Pediatric Acute Diseases, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Masanori Ikeda Okayama University School of Medicine Hirokazu Tsukahara Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Anti-inflammatory therapy, centered on inhaled steroids, suppresses airway inflammation in asthma, reduces asthma mortality and hospitalization rates, and achieves clinical remission in many pediatric patients. However, the spontaneous remission rate of childhood asthma in adulthood is not high, and airway inflammation and airway remodeling persist after remission of asthma symptoms. Childhood asthma impairs normal lung maturation, interferes with peak lung function in adolescence, reduces lung function in adulthood, and increases the risk of developing chronic obstructive pulmonary disease (COPD). Early suppression of airway inflammation in childhood and prevention of asthma exacerbations may improve lung maturation, leading to good lung function and prevention of adult COPD. Biological drugs that target T-helper 2 (Th2) cytokines are used in patients with severe pediatric asthma to reduce exacerbations and airway inflammation and improve respiratory function. They may also suppress airway remodeling in childhood and prevent respiratory deterioration in adulthood, reducing the risk of COPD and improving long-term prognosis. No studies have demonstrated a suppressive effect on airway remodeling in childhood severe asthma, and further clinical trials using airway imaging analysis are needed to ascertain the inhibitory effect of biological drugs on airway remodeling in severe childhood asthma. In this review, we describe the natural prognosis of lung function in childhood asthma and the risk of developing adult COPD, the pathophysiology of allergic airway inflammation and airway remodeling via Th2 cytokines, and the inhibitory effect of biological drugs on airway remodeling in childhood asthma. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0914-5087 80 3 2022 Innovative clinical pathway shortened the length of hospital stay and prevented readmission in patients with acute decompensated heart failure 232 239 EN Naofumi Amioka Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Takaishi Department of Cardiology, Mitoyo General Hospital Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toyohiro Endo Department of Cardiology, Mitoyo General Hospital Toshihiro Iida Department of Cardiology, Mitoyo General Hospital Tatsuya Yamaji Department of Cardiology, Mitoyo General Hospital Hisatoshi Mori Department of Cardiology, Mitoyo General Hospital Takao Kishinoue Department of Cardiology, Mitoyo General Hospital Kentaro Yasuhara Department of Cardiology, Mitoyo General Hospital Naoaki Matsuo Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Tanimoto Department of Cardiology, Mitoyo General Hospital Yukari Nakano Department of Cardiology, Mitoyo General Hospital Nobuhiko Onishi Department of Cardiology, Mitoyo General Hospital Masayuki Ueeda Department of Cardiology, Mitoyo General Hospital Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: With the rapidly aging population in Japan, the number of patients hospitalized for acute decompensated heart failure (ADHF) is increasing. Mitoyo General Hospital created an innovative clinical pathway (CP) for promoting early discharge in patients with ADHF. Major points of the CP were as follows: using tolvaptan as a standard therapy, completing the acute therapies within three days, and starting cardiac rehabilitation from the second day after admission. <br> Methods: We collected data for patients with ADHF who were admitted to our hospital before introduction of the CP (non-CP group) (April 2014-July 2015) and after introduction of the CP (CP group) (August 2015-July 2019). We investigated the impact of the CP on the length of hospital stay (LOHS) and readmission after discharge. <br> Results: After screening, 593 patients were enrolled in this study. After performing propensity score matching, 129 patients in the non-CP group and 129 patients in the CP group were analyzed. LOHS of patients in the CP group was significantly shorter than that of patients in the non-CP group [20 (14-28) days vs 12 (8-21) days] (p < 0.001) without an increase in mortality during hospitalization or an increase in the rate of readmission due to ADHF within 30 days. Use of the CP was an independent negative factor contributing to LOHS for patients with ADHF, even after adjustment of other factors including the use of tolvaptan (p < 0.001). The CP significantly decreased the proportion of patients readmitted to hospitals due to ADHF within 6 months [n = 32 (27%) vs n = 18 ( 15%), p = 0.026] and 1 year [n = 40 (34%) vs n = 23 ( 19%), p = 0.009] after discharge compared to the proportion in the non-CP group. <br> Conclusions: The CP significantly reduced the LOHS of patients without increasing the in-hospital mortality and it also reduced the risk of readmission in the mid-term and long-term. (c) 2021 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved. No potential conflict of interest relevant to this article was reported.

Japanese Pharmacological Society Acta Medica Okayama 1347-8613 150 1 2022 Novel aspects of sepsis pathophysiology: NETs, plasma glycoproteins, endotheliopathy and COVID-19 9 20 EN M. Nishibori Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences In 2016, sepsis was newly defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis remains one of the crucial medical problems to be solved worldwide. Although the world health organization has made sepsis a global health priority, there remain no specific and effective therapy for sepsis so far. Indeed, over the previous decades almost all attempts to develop novel drugs have failed. This may be partly ascribable to the multifactorial complexity of the septic cascade and the resultant difficulties of identifying drug targets. In addition, there might still be missing links among dysregulated host responses in vital organs. In this review article, recent advances in understanding of the complex pathophysiology of sepsis are summarized, with a focus on neutrophil extracellular traps (NETs), the significant role of NETs in thrombosis/embolism, and the functional roles of plasma proteins, histidine-rich glycoprotein (HRG) and inter-alpha-inhibitor proteins (IAIPs). The specific plasma proteins that are markedly decreased in the acute phase of sepsis may play important roles in the regulation of blood cells, vascular endothelial cells and coagulation. The accumulating evidence may provide us with insights into a novel aspect of the pathophysiology of sepsis and septic ARDS, including that in COVID-19. No potential conflict of interest relevant to this article was reported.

Japan Academy Acta Medica Okayama 0386-2208 98 6 2022 On the origin and evolution of the asteroid Ryugu: A comprehensive geochemical perspective 227 282 EN Eizo NAKAMURA The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Katsura KOBAYASHI The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Ryoji TANAKA The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Tak KUNIHIRO The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Hiroshi KITAGAWA The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Christian POTISZIL The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Tsutomu OTA The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Chie SAKAGUCHI The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Masahiro YAMANAKA The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Dilan M. RATNAYAKE The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Havishk TRIPATHI The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Rahul KUMAR The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Maya-Liliana AVRAMESCU The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Hidehisa TSUCHIDA The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Yusuke YACHI The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Hitoshi MIURA Department of Information and Basic Science, Nagoya City University Masanao ABE The Graduate University for Advanced Studies (SOKENDAI) Ryota FUKAI Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Shizuho FURUYA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Kentaro HATAKEDA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Tasuku HAYASHI Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Yuya HITOMI Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Kazuya KUMAGAI Marine Works Japan, Ltd. Akiko MIYAZAKI Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Aiko NAKATO Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Masahiro NISHIMURA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Tatsuaki OKADA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Hiromichi SOEJIMA Marine Works Japan, Ltd. Seiji SUGITA Graduate School of Science, The University of Tokyo Ayako SUZUKI Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Tomohiro USUI Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Toru YADA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Daiki YAMAMOTO Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Kasumi YOGATA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Miwa YOSHITAKE Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Masahiko ARAKAWA Graduate School of Science, Kobe University Atsushi FUJII Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Masahiko HAYAKAWA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Naoyuki HIRATA Graduate School of Science, Kobe University Naru HIRATA Faculty of Computer Science and Engineering, The University of Aizu Rie HONDA Faculty of Science and Technology, Kochi University Chikatoshi HONDA Faculty of Computer Science and Engineering, The University of Aizu Satoshi HOSODA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Yu-ichi IIJIMA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Hitoshi IKEDA Research and Development Directorate, JAXA Masateru ISHIGURO Department of Physics and Astronomy, Seoul National University Yoshiaki ISHIHARA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Takahiro IWATA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Kosuke KAWAHARA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Shota KIKUCHI Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Kohei KITAZATO Faculty of Computer Science and Engineering, The University of Aizu Koji MATSUMOTO National Astronomical Observatory of Japan Moe MATSUOKA Observatoire de Paris Tatsuhiro MICHIKAMI Faculty of Engineering, Kindai University Yuya MIMASU Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Akira MIURA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Tomokatsu MOROTA Graduate School of Environmental Studies, Nagoya University Satoru NAKAZAWA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Noriyuki NAMIKI National Astronomical Observatory of Japan Hirotomo NODA National Astronomical Observatory of Japan Rina NOGUCHI Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Naoko OGAWA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Kazunori OGAWA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Chisato OKAMOTO Graduate School of Science, Kobe University Go ONO Research and Development Directorate, JAXA Masanobu OZAKI Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Takanao SAIKI Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Naoya SAKATANI College of Science, Rikkyo University Hirotaka SAWADA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Hiroki SENSHU Planetary Exploration Research Center (PERC), Chiba Institute of Technology Yuri SHIMAKI Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Kei SHIRAI Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Yuto TAKEI Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Hiroshi TAKEUCHI Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Satoshi TANAKA The Graduate University for Advanced Studies (SOKENDAI) Eri TATSUMI Graduate School of Science, The University of Tokyo Fuyuto TERUI Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Ryudo TSUKIZAKI Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Koji WADA Planetary Exploration Research Center (PERC), Chiba Institute of Technology Manabu YAMADA Planetary Exploration Research Center (PERC), Chiba Institute of Technology Tetsuya YAMADA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Yukio YAMAMOTO Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Hajime YANO Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Yasuhiro YOKOTA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Keisuke YOSHIHARA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Makoto YOSHIKAWA The Graduate University for Advanced Studies (SOKENDAI) Kent YOSHIKAWA Research and Development Directorate, JAXA Masaki FUJIMOTO Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Sei-ichiro WATANABE Graduate School of Environmental Studies, Nagoya University Yuichi TSUDA Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency Presented here are the observations and interpretations from a comprehensive analysis of 16 representative particles returned from the C-type asteroid Ryugu by the Hayabusa2 mission. On average Ryugu particles consist of 50% phyllosilicate matrix, 41% porosity and 9% minor phases, including organic matter. The abundances of 70 elements from the particles are in close agreement with those of CI chondrites. Bulk Ryugu particles show higher ƒΒ18O, ƒ’17O, and ƒΓ54Cr values than CI chondrites. As such, Ryugu sampled the most primitive and least-thermally processed protosolar nebula reservoirs. Such a finding is consistent with multi-scale H-C-N isotopic compositions that are compatible with an origin for Ryugu organic matter within both the protosolar nebula and the interstellar medium. The analytical data obtained here, suggests that complex soluble organic matter formed during aqueous alteration on the Ryugu progenitor planetesimal (several 10fs of km), <2.6 Myr after CAI formation. Subsequently, the Ryugu progenitor planetesimal was fragmented and evolved into the current asteroid Ryugu through sublimation. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1420-3049 27 12 2022 Rational Design of Peptides Derived from Odorant-Binding Proteins for SARS-CoV-2-Related Volatile Organic Compounds Recognition 3917 EN Jin Wang Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kenji Sakai Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toshihiko Kiwa Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Peptides are promising molecular-binding elements and have attracted great interest in novel biosensor development. In this study, a series of peptides derived from odorant-binding proteins (OBPs) were rationally designed for recognition of SARS-CoV-2-related volatile organic compounds (VOCs). Ethanol, nonanal, benzaldehyde, acetic acid, and acetone were selected as representative VOCs in the exhaled breath during the COVID-19 infection. Computational docking and prediction tools were utilized for OBPs peptide characterization and analysis. Multiple parameters, including the docking model, binding affinity, sequence specification, and structural folding, were investigated. The results demonstrated a rational, rapid, and efficient approach for designing breath-borne VOC-recognition peptides, which could further improve the biosensor performance for pioneering COVID-19 screening and many other applications. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 23 11 2022 Molecular and Genetic Interactions between CCN2 and CCN3 behind Their Yin-Yang Collaboration 5887 EN Satoshi Kubota Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazumi Kawata Department of Biochemistry and Molecular Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takako Hattori Department of Biochemistry and Molecular Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Nishida Department of Biochemistry and Molecular Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Cellular communication network factor (CCN) 2 and 3 are the members of the CCN family that conduct the harmonized development of a variety of tissues and organs under interaction with multiple biomolecules in the microenvironment. Despite their striking structural similarities, these two members show contrastive molecular functions as well as temporospatial emergence in living tissues. Typically, CCN2 promotes cell growth, whereas CCN3 restrains it. Where CCN2 is produced, CCN3 disappears. Nevertheless, these two proteins collaborate together to execute their mission in a yin-yang fashion. The apparent functional counteractions of CCN2 and CCN3 can be ascribed to their direct molecular interaction and interference over the cofactors that are shared by the two. Recent studies have revealed the mutual negative regulation systems between CCN2 and CCN3. Moreover, the simultaneous and bidirectional regulatory system of CCN2 and CCN3 is also being clarified. It is of particular note that these regulations were found to be closely associated with glycolysis, a fundamental procedure of energy metabolism. Here, the molecular interplay and metabolic gene regulation that enable the yin-yang collaboration of CCN2 and CCN3 typically found in cartilage development/regeneration and fibrosis are described. No potential conflict of interest relevant to this article was reported.