Springer Science and Business Media LLC Acta Medica Okayama 2662-4443 6 1 2025 From localized 4f electrons to anisotropic exchange interactions in ferromagnetic CeRh6Ge4 269 EN Shoichiro Itokazu Department of Physics, Okayama University Akimitsu Kirikoshi Research Institute for Interdisciplinary Science, Okayama University Harald O. Jeschke Research Institute for Interdisciplinary Science, Okayama University Junya Otsuki Research Institute for Interdisciplinary Science, Okayama University CeRh6Ge4 is a cerium-based ferromagnetic material exhibiting a quantum critical behavior under pressure. We derive effective exchange interactions, using the framework of density functional theory combined with dynamical mean-field theory. Our results reveal that the nearest-neighbor ferromagnetic interaction along the c axis is isotropic in spin space, leading to a formation of spin chains. On the other hand, the inter-chain coupling is highly anisotropic: The in-plane moment weakly interacts ferromagnetically in the a–b plane to stabilize the ferromagnetic state, whereas the z-component couples antiferromagnetically, contributing to its destabilization. The magnetic anisotropy of the interchain interactions as well as of the local 4f wavefunctions characterizes the magnetic properties underlying the ferromagnetic transition and the quantum critical behavior in CeRh6Ge4. No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構教師教育開発センター Acta Medica Okayama 2186-1323 16 2026 ドイツ付近の夏の気候とシューベルトの歌曲《春に》異質な他者との出会いを促す大学での学際的授業の報告 75 89 EN Kuranoshin KATO Faculty of Education, Okayama University Isao NAGAOKA Faculty of Education, Okayama University Haruko KATO Faculty of Education, Gufu Shotoku Gakuen University (Former affiliation) 10.18926/CTED/70361 　「異質な他者」への出会いを促す授業例の更なる蓄積のため，ドイツ付近の「夏」の気候と季節感に注目した教科横断的な授業を大学で実践した。授業では，ドイツ付近の気候と季節サイクルの中での「夏」の特徴を把握すると共に，シューベルトの歌曲《春に》を鑑賞した。《春に》の3 番の「夏の間じゅう，ずっと」という歌詞で歌われている情景や情感が，ドイツ付近と日本付近を想定した場合にどう違い得るか，に関する受講生の記述を分析した。その結果，日本の夏の高温多湿な環境からは原詩の情感そのものが成立し難いと感じた学生もいるなど，本実践は，自分たちの「当たり前」とは異なる気候や季節感にも目を向ける機会になり得たといえる。一方，日本とはかなり違う気候背景の中でシューベルトが思い描いたであろう情景・心情に授業で深く迫るための，音楽表現自体への踏み込み方についても，今後検討する必要性が示唆された。 No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-0851 75 3 2026 A real-world comparison of nivolumab plus cabozantinib and pembrolizumab plus lenvatinib focusing on safety outcomes in metastatic renal cell carcinoma: results from the JK-FOOT consortium 84 EN Takafumi Yanagisawa Department of Urology, The Jikei University School of Medicine Keiichiro Mori Department of Urology, The Jikei University School of Medicine Tatsushi Kawada Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Satoshi Katayama Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Takuya Tsujino Department of Urology, Osaka Medical and Pharmaceutical University Ryoichi Maenosono Department of Urology, Osaka Medical and Pharmaceutical University Shingo Toyoda Department of Urology, Faculty of Medicine, Kindai University Takuhisa Nukaya Department of Urology, Fujita-Health University School of Medicine Hirofumi Morinaka Department of Urology, Kawasaki Medical School Keita Tamura Department of Urology, Hamamatsu Medical University Wataru Fukuokaya Department of Urology, The Jikei University School of Medicine Fumihiko Urabe Department of Urology, The Jikei University School of Medicine Masaya Murakami Department of Urology, The Jikei University School of Medicine Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kiyoshi Takahara Department of Urology, Fujita-Health University School of Medicine Kazutoshi Fujita Department of Urology, Faculty of Medicine, Kindai University Haruhito Azuma Department of Urology, Osaka Medical and Pharmaceutical University Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Teruo Inamoto Department of Urology, Hamamatsu Medical University Kazumasa Komura Department of Urology, Kawasaki Medical School Takahiro Kimura Department of Urology, The Jikei University School of Medicine Purpose Immune checkpoint inhibitor (ICI)-based combination therapy is a standard first-line treatment for metastatic renal cell carcinoma (mRCC), with combinations such as nivolumab plus cabozantinib (Nivo + Cabo) and pembrolizumab plus lenvatinib (Pem + Len) demonstrating favorable oncologic outcomes. However, no direct comparisons between these two regimens have been conducted. This study aimed to compare the safety and oncologic outcomes of Nivo + Cabo and Pem + Len in patients with mRCC. Methods This retrospective study included 185 patients with mRCC treated with Nivo + Cabo (n = 81) or Pem + Len (n = 104) between January 2018 and June 2025 across multiple institutions. The primary outcome was a comparison of treatment-related adverse events (TrAEs). Oncologic outcomes, including objective response rate (ORR), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS), were compared using one-to-one propensity score matching. Results Any-grade TrAEs occurred in 90% of patients in the Nivo + Cabo group and 92% in the Pem + Len group (p = 0.6). Severe TrAEs (grade ≥ 3) were more frequent in the Pem + Len group (44%) than in the Nivo + Cabo group (30%, p = 0.048). Tyrosine kinase inhibitor dose reduction and treatment discontinuation rates were similar between groups. In the matched cohort (Nivo + Cabo: n = 74; Pem + Len: n = 74), ORRs were comparable (66% vs. 71%, p = 0.6). With a median follow-up of 17 months, no significant differences were observed in PFS (p = 0.4), CSS (p = 0.9), or OS (p = 0.5). Conclusions Nivo + Cabo and Pem + Len demonstrated similar oncologic efficacy as first-line treatments for mRCC. However, Pem + Len was associated with more severe TrAEs. Careful toxicity management and shared decision-making are essential when selecting ICI-based combinations. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2410-387X 9 4 2025 Role-Based Efficient Proactive Secret Sharing with User Revocation 80 EN Yixuan He Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuta Kodera Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yasuyuki Nogami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Samsul Huda Interdisciplinary Education and Research Field, Okayama University Proactive secret sharing (PSS), an extension of secret-sharing schemes, safeguards sensitive data in dynamic distributed networks by periodically refreshing shares to counter adversarial attacks. In our previous work, we constructed a non-interactive proactive secret scheme by integrating threshold homomorphic encryption (ThHE) while reducing the communication complexity to 𝑂(𝑛). Not only is refreshing shares important but revoking the shares of users who have left the system is also essential in practical dynamic membership scenarios. However, the previous work was insufficient for supporting explicit user revocation. This study strengthens the description of roles for authorized users and proposes a scheme to achieve non-interactive share refresh and dynamic user management. In each epoch, authorized users are classified into three roles: retain, newly join, and rejoin, and they receive a broadcast of the compact ciphertext encoding both the refresh information and the revocation instructions from the trusted center (dealer). Authorized users independently derive new shares through homomorphic computations, whereas revoked users are unable to generate new shares. Hash functions are used to bind revocation parameters to the cryptographic hashes of valid users in order to guarantee integrity during revocation, allowing for effective verification without compromising non-interactivity. Our new scheme not only extends the revocation structure but also preserves the 𝑂(𝑛) communication complexity. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1424-8220 25 21 2025 Integrated Authentication Server Design for Efficient Kerberos–Blockchain VANET Authentication 6651 EN Maya Rahayu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Md. Biplob Hossain Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Samsul Huda Interdisciplinary Education and Research Field, Okayama University Yasuyuki Nogami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Vehicular Ad Hoc Network (VANET) is a fundamental component of the intelligent transportation systems (ITS), providing critical road information to users. However, the volatility of VANETs creates significant vulnerabilities from malicious actors. Thus, verifying joining entities is crucial to maintaining the VANET’s communication security. Authentication delays must stay below 100 ms to meet VANET requirements, posing a major challenge for security. Our previous research introduced a Kerberos–Blockchain (KBC) authentication system that contains two main components separately: Authentication Server (AS) and Ticket Granting Server (TGS). However, this KBC architecture required an additional server to accommodate increasing vehicle volumes in urban environments, leading to higher infrastructure costs. This paper presents an integrated authentication server that merges AS and TGS into a Combined Server (CBS) while retaining blockchain security. We evaluate it using OMNeT++ with SUMO for traffic simulation and Ganache for blockchain implementation. Results show that CBS removes the need for an extra server while keeping authentication delays under 100 ms. It also improves throughput by 104% and reduces signaling overhead by 45% compared to KBC. By optimizing authentication without compromising security, the integrated server greatly enhances the cost-effectiveness and efficiency of VANET systems. No potential conflict of interest relevant to this article was reported.

BON VIEW PUBLISHING PTE Acta Medica Okayama 2810-9503 5 1 2025 A Study on Zeek IDS Effectiveness for Cybersecurity in Agricultural IoT Networks 133 142 EN Samsul Huda Interdisciplinary Education and Research Field, Okayama University Muhammad Bisri Musthafa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University S. M. Shamim Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yasuyuki Nogami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University As agriculture moves toward Agriculture 4.0, which uses Internet of Things (IoT) devices to collect data in real time and monitor things from a distance, these networks are becoming increasingly vulnerable to cyberattacks. A common method used to protect against these kinds of threats is the use of intrusion detection systems (IDS). However, the agricultural environment is often changing and has limited resources, which makes cybersecurity challenging. Several available IDS tools are not designed to work properly in places with few resources, intermittent access, and unpredictable network conditions. This paper investigates the performance of Zeek, an open-source IDS, in identifying potential threats in agricultural IoT networks. We performed both offline and real-time experiments: offline analysis used pcap files from the Stratosphere Laboratory dataset, and real-time evaluation involved simulated live attack scenarios, focusing on unauthorized access attempts and distributed denial-of-service (DDoS) attacks. Zeek's performance was assessed based on CPU and memory utilization, as well as quality of service (QoS) metrics. From the experimental results, we found that Zeek was quite effective in protecting agricultural IoT networks against typical threats. Memory usage remained stable around 5% during offline analysis and under 20% during active attacks. However, CPU usage was more volatile, peaking at 120% during DDoS events. In terms of QoS, the system maintained a good throughput (1,375 kbits/s) with minimal packet loss (0.000186%). Among the attack types that we tested, brute force attacks, which represent attempts at unauthorized access, had the strongest effect on network performance, increasing delay to 2.159 ms and jitter to 0.793 ms. It seems clear that a heavier traffic load during such attacks can interfere with QoS. On the basis of our observation, we recommend practical deployment strategies for agricultural IoT systems that take these limitations into consideration, aiming to keep networks both secure and efficient under pressure. No potential conflict of interest relevant to this article was reported.

岡山大学大学院ヘルスシステム統合科学研究科 Acta Medica Okayama 2436-3227 6 2026 2025 年度次世代医療機器開発人材育成プログラム BIZEN デバイスデザインコースの取り組み 59 68 EN Tsuneaki TSUZUKI Center for Innovative Clinical Medicine, Okayama University Hospital Daisuke UCHIDA Center for Innovative Clinical Medicine, Okayama University Hospital Toshio KISHIMOTO Organization for Research and Innovation Strategy, Okayama University Yoshinari SENGOKU Center for Innovative Clinical Medicine, Okayama University Hospital Toshio KORENAGA Organization for Research and Innovation Strategy, Okayama University Yu HITOBE Center for Innovative Clinical Medicine, Okayama University Hospital Yasuyuki YOSHIBA Academic Field of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jun SAKURAI Center for Innovative Clinical Medicine, Okayama University Hospital 10.18926/interdisciplinary/70331 No potential conflict of interest relevant to this article was reported.

岡山大学大学院ヘルスシステム統合科学研究科 Acta Medica Okayama 2436-3227 6 2026 2025 年度における「先進病院実習」の取り組み 49 57 EN Mizuki MORITA Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masaki MAGARI Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jin Wang Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toyohiko WATANABE Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masataka OITA Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Nahoko HARADA Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Keisuke SHISHIDO Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University 10.18926/interdisciplinary/70330 No potential conflict of interest relevant to this article was reported.

John Wiley & Sons Ltd. Acta Medica Okayama 2314-6133 2025 2025 Comparing the Activity of Peripheral Blood Mononuclear Cells Frozen Under Electromagnetic Field Freezing and Standard Slow-Freezing 9884345 EN Takehiro Matsubara Okayama University Hospital Biobank Mina Takagi Faculty of Health Sciences, Okayama University Medical School Takahiro Uwabo Department of Biorepository Research and Networking, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junichi Soh Department of Thoracic Surgery, Osaka Metropolitan University Graduate School of Medicine Shinichi Toyooka Okayama University Hospital Biobank Mizuki Morita Okayama University Hospital Biobank Peripheral blood mononuclear cells (PBMCs) are cells obtained from the blood that are used not only in clinical tests but also in various research applications. The slow-freezing (SLF) method, currently the standard for PBMC cryopreservation, involves extended storage at −80°C before transfer to liquid nitrogen. Delays in this transfer, such as overnight or weekend holds, risk a gradual decline in cell viability. Additionally, variability in freezing duration can lead to inconsistent cell quality, emphasizing the need for an alternative freezing method that allows for more timely transfer to liquid nitrogen. This study is aimed at clarifying whether the method of using a freezer with an applied electromagnetic field (EMF) is superior to the currently used standard SLF method for PBMC cryopreservation. A comparison of the number of viable cells, cell viability, and cell activity showed that the EMF method was equivalent to the SLF method. However, the shortest time required for freezing was significantly shorter with the EMF method than the SLF method (0.25 vs. 3 h), allowing for earlier transfer of PBMC to liquid nitrogen. This demonstrates that the EMF method offers an advantage in operational efficiency, particularly for facilities that routinely process and store PBMCs, such as biobanks and other storage-focused departments. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0923-1811 119 1 2025 Big data-driven target identification by machine learning: DRD2 as a therapeutic target for psoriasis 9 17 EN Takashi Sakai Department of Dermatology, Faculty of Medicine, Oita University Ryusuke Sawada Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Otoha Ichinose Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology Takeshi Terabayashi Department of Pharmacology, Faculty of Medicine, Oita University Yutaka Hatano Department of Dermatology, Faculty of Medicine, Oita University Yoshihiro Yamanishi Department of Complex Systems Science, Graduate School of Informatics, Nagoya University Toshimasa Ishizaki Department of Pharmacology, Faculty of Medicine, Oita University Background: The development of medical treatments has traditionally relied on researchers leveraging scientific knowledge to hypothesize disease mechanisms and identify therapeutic agents. However, the depletion of novel therapeutic targets has become a significant challenge, resulting in stagnation within pharmaceutical research. Objective: To address the scarcity of therapeutic targets, we developed a machine learning (ML)-based system capable of predicting therapeutic target molecules for diseases. To validate its utility, we applied this system to psoriasis, aiming to identify novel treatment strategies. Methods: Our approach utilized a large clinical database to calculate reporting odds ratios for all drugs associated with the prevention of diseases of interest. We identified target proteins by analyzing large chemical structure databases to discover proteins commonly associated with preventive drug candidates. Experimental validation was conducted by administering a predicted therapeutic candidate in an imiquimod-induced psoriasis mouse model. Results: The ML-based predictions identified drugs for Parkinson’s disease as potential preventive candidates for psoriasis. Further analysis highlighted dopamine receptor D2 (DRD2) as a therapeutic target. Administration of a DRD2 agonist alleviated psoriasis symptoms in mice, evidenced by the downregulation of mRNA expression in the IL-17 pathway and reduced serum tumor necrosis factor-α levels. Conclusion: This study demonstrates the utility of a novel ML-based system for identifying therapeutic targets, as shown by its successful application in uncovering the role of DRD2 in psoriasis. Beyond psoriasis, this system offers significant potential for exploring pathological mechanisms and discovering therapeutic targets across various diseases. No potential conflict of interest relevant to this article was reported.

Japan Society of Mechanical Engineers Acta Medica Okayama 1880-5558 20 1 2025 Numerical analysis validating the standard k-epsilon model for the kinetic energy of turbulence subjected to weak but long-lasting wind tunnel blockage acceleration JFST0004 EN Akira ONO Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroki SUZUKI Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Toshinori KOUCHI Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kento TANAKA Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The aim of this study is to investigate the effect of weak but prolonged mean flow accelerations, such as those observed in wind tunnel blockage acceleration, on free-stream turbulence. Specifically, this research aims to validate a model previously developed based on the k-epsilon model. To test this model, the study focuses on scenarios where the turbulence under acceleration is steady and isotropic, since the model suggests that this type of acceleration has no effect on the turbulent kinetic energy. To examine this suggestion, the turbulence within a periodic box was analyzed using large-eddy simulation (LES) based on the conventional Smagorinsky model framework. The numerical analysis is based on a method that conserves velocity fluctuation intensities. The results show that while high rate of acceleration deviates turbulent kinetic energy, low rate acceleration has hardly any effect on turbulent kinetic energy, enstrophy, pressure fluctuation, relative pressure fluctuation intensity, and higher-order statistics of a velocity fluctuation. These results validate the accuracy of the model proposed in the previous studies. These results were obtained by focusing on differences in Reynolds numbers and the spatial scale of the forcing. No potential conflict of interest relevant to this article was reported.

Universitas Islam Negeri Alauddin Makassar Acta Medica Okayama 2548-5334 17 2 2025 Trend of adjusted antenatal care visits on pregnant women and neonatal during the COVID-19 pandemic: Findings from a three districts survey in 2021 110 118 EN Juliani Ibrahim Departement of Public Health, Faculty of Medicine and Health Science, Universitas Muhammadiyah Makassar Yoko Takahata Nursing of Department, Graduate School of Health Science, Okayama University Sukaeni Ibrahim Faculty of Medicine, Bosowa University Sustainable health development efforts amid infectious disease outbreaks such as Coronavirus disease 2019 (COVID-19) require a resilient maternal health system. With cases rising globally and across Asia, Indonesia faces significant disruptions in essential services. A critical research gap exist in utilizing adjusted time-series analysis to isolated pandemic impact from seasonal variation in urban Indonesia. This study evaluates trends in antenatal care (ANC) visits (January 2019–December 2020) at three Community Health Centres in Makassar: Bara-Baraya, Jongaya and Batua using Interrupted Time Series (ITS) analysis. Findings reveal a significant decline in visits during the second and third quarters of 2020, primarily due to transmission fears. We suggest integration of telemedicine and home visits to maintain continuity of care. Although focused on urban Makassar, these results are an important reference for health and offer applicable solutions for other developing countries facing resource constraints. This study emphasizes the need for inclusive prevention strategies to protect maternal health in urban and rural areas in low- to middle-income countries during systemic health crises. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2211-7156 18 2025 Development of FTase inhibitors inspired by the structures of andrastins 102828 EN Fumino Kitamura Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama Masaru Tanioka Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama Ayano Kosaka Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama Nao Matsuzawa Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama Takayuki Obita Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama Yuko Sakajiri Tomokazu Shibata Department of Complex Systems Science, Graduate School of Informatics, Nagoya University Ryusuke Sawada Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeshi Yokoyama Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama Aki Kohyama Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama Tsuyoshi Yamada Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama Yoshihiro Yamanishi Department of Complex Systems Science, Graduate School of Informatics, Nagoya University Mineyuki Mizuguchi Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama Yuji Matsuya Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama We designed and synthesized structurally simple farnesyl transferase (FTase) inhibitors (1a–1d) by leveraging andrastin, a natural product with FTase inhibitory activity. 1a–1d possess a cyclopentane-1,3-dione core, which is critical for FTase recognition; a farnesyl moiety, which is a simplified motif of A to C rings of andrastin; and a carboxylic acid or methoxycarbonyl group, which enables multipoint hydrogen bonding interactions with FTase. Competitive inhibition experiments revealed that 1d has the most potent FTase inhibitory activity. Docking simulation analysis of 1a–1d with FTase suggested that the multipoint hydrogen bonding interactions between the cyclopentane-1,3-dione moiety and the carboxyl group play an important role in FTase recognition. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1353-8020 143 2026 Biallelic CAG repeat expansion in the ATXN2 gene presenting with parkinsonism and spasticity 108168 EN Yosuke Osakada Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chika Matsuoka Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumiko Nakano Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Taira Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Fukui Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuko Kawahara Department of Neurology, Okayama Saiseikai General Hospital Yumiko Kutoku Department of Neurology, Kawasaki Medical School Manabu Takaki Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Osamu Yokota Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Ishiura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

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

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. 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. 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. 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.

Elsevier BV Acta Medica Okayama 0145-305X 165 2025 Local immune response induced by intra-fin antigen injection in Japanese medaka (Oryzias latipes) is a useful model for immunological studies 105344 EN Tsukasa Ryu Graduate School of Bioresource and Bioenvironmental Sciences, Laboratory of Marine Biochemistry, Kyushu University Mizuki Yoshino Graduate School of Bioresource and Bioenvironmental Sciences, Laboratory of Marine Biology, Kyushu University William Ka Fai Tse Graduate School of Bioresource and Bioenvironmental Sciences, Laboratory of Developmental Disorders and Toxicology, Kyushu University Satoshi Ansai Ushimado Marine Institute, Faculty of Science, Okayama University Taisen Iguchi Graduate School of Nanobioscience, Yokohama City University Anu Kumar Commonwealth Scientific and Industrial Research Organisation, CSIRO Environment Tomonori Somamoto Graduate School of Bioresource and Bioenvironmental Sciences, Laboratory of Marine Biochemistry, Kyushu University Miki Nakao Graduate School of Bioresource and Bioenvironmental Sciences, Laboratory of Marine Biochemistry, Kyushu University Yukiko Ogino Center for Promotion of International Education and Research, Faculty of Agriculture, Kyushu University Teleost fishes play a pivotal role in advancing our understanding of immune system evolution because they retain the ancient characteristics of vertebrate immunity, encompassing both innate and adaptive immune systems. Among these, innate immunity plays a critical role in fish as the first line of defense, coordinating rapid responses to pathogen infections. However, the lack of fish-specific immunological methodologies has limited progress in elucidating fish immune mechanisms. To better understand how the innate immune response develops and resolves in fish, detailed observation and integrative analysis of leukocytes at multiple time points is necessary. In the present study, an intra-fin injection method for observing local immune responses in Japanese medaka (Oryzias latipes) was tested and optimized to analyze the progression of zymosan-induced innate immune responses. Zymosan-injected medaka showed a rapid immune response characterized by leukocyte recruitment and phagocytosis. Using TG(FmpxP:mCherry) transgenic medaka with mCherry fluorescence driven by myeloperoxidase (mpx) promoter, granulocyte chemotaxis towards the site of zymosan entry was successfully visualized. The rapid increase in tumor necrosis factor α (tnfa), interleukin-1β (il1b), interleukin-6 (il6), and CXC motif chemokine ligand 8 (cxcl8) expressions in zymosan-injected anal fins provided a molecular basis for the visualized tissue-specific cellular response. Our study underscores the dynamic orchestration of immune components during the innate immune response in Japanese medaka and highlights their potential as a promising model for immunological research. No potential conflict of interest relevant to this article was reported.

American Society for Clinical Investigation Acta Medica Okayama 2379-3708 11 3 2025 Collagen-binding C-type natriuretic peptide enhances chondrogenesis and osteogenesis e198959 EN Kenta Hirai Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenta Sawamura Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Ryusaku Esaki Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Ryusuke Sawada Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuka Okusha Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eriko Aoyama Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Hiroki Saito Department of Orthopaedic Surgery, Kitasato University School of Medicine Kentaro Uchida Department of Orthopaedic Surgery, Kitasato University School of Medicine Takehiko Mima Department of Medical Technology, Faculty of Health Sciences, Ehime Prefectural University of Health Sciences Satoshi Kubota Department of Biochemistry and Molecular DentistryBacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shiro Imagama Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Masaki Matsushita Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Osamu Matsushita Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuyuki Hosono Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences C-type natriuretic peptide (CNP) is known to promote chondrocyte proliferation and bone formation; however, CNP’s extremely short half-life necessitates continuous intravascular administration to achieve bone-lengthening effects. Vosoritide, a CNP analog designed for resistance to neutral endopeptidase, allows for once-daily administration. Nonetheless, it distributes systemically rather than localizing to target tissues, which may result in adverse effects such as hypotension. To enhance local drug delivery and therapeutic efficacy, we developed a potentially novel synthetic protein by fusing a collagen-binding domain (CBD) to CNP, termed CBD-CNP. This fusion protein exhibited stability under heat conditions and retained the collagen-binding ability and bioactivity as CNP. CBD-CNP localized to articular cartilage in fetal murine tibiae and promoted bone elongation. Spatial transcriptomic analysis revealed that the upregulation of chondromodulin expression may contribute to its therapeutic effects. Treatment of CBD-CNP mixed with collagen powder to a fracture site of a mouse model increased bone mineral content and bone volume compared with CNP-22. Intraarticular injection of CBD-CNP to a mouse model of knee osteoarthritis suppressed subchondral bone thickening. By addressing the limitations of CNP’s rapid degeneration, CBD-CNP leverages its collagen-binding capacity to achieve targeted, sustained delivery in collagen-rich tissues, offering a promising strategy for enhancing chondrogenesis and osteogenesis. 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. 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. 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.

Springer Science and Business Media LLC Acta Medica Okayama 2041-4889 16 1 2025 TRPV2 in muscle satellite cells is crucial for skeletal muscle remodelling 888 EN Yanzhu Chen Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kimiaki Katanosaka Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University Makoto Shibuya Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yubing Dong Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Lidan Zhang Laboratory of Stem Cell Regeneration and Adaptation, Graduate School of Pharmaceutical Sciences, The University of Osaka Motoi Kanagawa Department of Cell Biology and Molecular Medicine, Ehime University Graduate School of Medicine So-ichiro Fukada Laboratory of Stem Cell Regeneration and Adaptation, Graduate School of Pharmaceutical Sciences, The University of Osaka Keiji Naruse Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Katanosaka Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Skeletal muscle remodelling relies on muscle stem cells (MuSCs) for regeneration after injury and hypertrophy in response to mechanical loading. However, the mechanisms that trigger MuSC activation and proliferation remain unclear. Transient receptor potential vanilloid 2 (TRPV2) ion channels respond to insulin-like growth factor-1 and mechanical stimuli to regulate the biological characteristics of various cells. Using a temporally inducible MuSC-specific conditional knockout (cKO) mouse, we show that TRPV2 regulates MuSC function and is essential for muscle remodelling. In cultured myofibre, MuSCs express TRPV2 and exhibit Ca2+ responses to the TRPV2 agonists 2-aminoethoxydiphenyl borate and probenecid, which are abolished upon TRPV2 deletion. TRPV2-deficient MuSCs exhibit reduced paired box 7 (Pax7) expression and impaired proliferation, suggesting TRPV2 is a factor that regulates the early stage of MuSC function. Myotube formation in MuSCs was enhanced by overexpression of TRPV2 and suppressed by TRPV2 deficiency, suggesting that TRPV2 is a factor that promotes myogenesis. Muscle-administered cardiotoxin promoted muscle regeneration and resulted in the appearance of numerous Pax7-positive MuSCs between myofibres. MuSC-specific TRPV2 cKO mice exhibit substantially impaired muscle regeneration after cardiotoxin-induced injury, drastically reducing Pax7-positive MuSCs between myofibres. In floxed mice, mechanical loading via synergist ablation induces hypertrophy and greatly increases the number of myonuclei per myofibre. In contrast, MuSC-specific TRPV2 cKO mice show no changes in myofibre thickness or nuclear number, either at baseline or after mechanical loading. Mechanical loading of floxed mice increased TRPV2+/Pax7+ double-positive MuSCs, but MuSC-specific TRPV2 cKO mice showed no change. Additionally, MuSCs exhibit Ca2+ responses to hypo-osmotic stimuli, which are suppressed by TRPV2 inhibitors and TRPV2 deletion, suggesting that MuSCs exhibit TRPV2-dependent mechanical responses. These results establish TRPV2 as a critical regulator of MuSC-mediated muscle remodelling, an important finding that may lead to therapeutic strategies for muscle repair and adaptation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1435-2451 411 1 2025 The impact of liver transection depth on surgical difficulty in robotic versus laparoscopic limited liver resection (TAKUMI-5) 22 EN Tomokazu Fuji Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kosei Takagi Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kazuya Yasui Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Atene Ito Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takeyoshi Nishiyama Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuo Nagai Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shohei Yokoyama Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Purpose Although robotic liver resection (RLR) has gained popularity worldwide, limited liver resection remains the mainstay of RLR. This study aimed to investigate the effect of parameters, including liver transection depth (LTD), on surgical difficulty in limited RLR compared with limited laparoscopic liver resection (LLR). Methods This retrospective study included 105 patients who underwent limited RLR (n = 56) or LLR (n = 49) at our institution between January 2018 and December 2024. After comparing outcomes of RLR and LLR, multivariate analyses were performed to examine effect of LTD on surgical difficulty (defined as prolonged operative time). Moreover, outcomes stratified by LTD cut-off values were compared between the groups. Results Median LTD was similar between groups (RLR vs. LLR: 2.6 vs. 2.6 cm, P = 0.77). LTD was significantly correlated with operative time for both procedures (RLR, R² = 0.07, P = 0.042; LLR, R² = 0.08, P = 0.046). Multivariate analyses demonstrated that LLR (odds ratio, 6.9; P < 0.001) and LTD (odds ratio, 2.0; P = 0.004) were significant risk factors of surgical difficulty. Among patients with deeper LTD (> 2.5 cm), the RLR group had significantly shorter operative time (145 vs. 231 min, P < 0.001), less blood loss (nil vs. 100 mL, P = 0.006), and a higher rate of textbook outcomes (76.7% vs. 42.3%, P = 0.01). Conclusion This study investigated impact of LTD on surgical outcomes in patients who underwent limited RLR compared to those who underwent limited LLR. LTD may be a useful parameter for estimating surgical difficulty in limited RLR. Moreover, robotic surgery may be favorable for deeper and limited liver resections. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1462-8910 27 10 2025 D3 lymph node dissection in colon cancer patients aged 90 years and over: Is it justified? A multi‐institutional retrospective study e70269 EN Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Hospital Satoe Takanaga Department of Gastroenterological Surgery, Okayama University Hospital Ryo Inada Department of Surgery, Kochi Health Sciences Center Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Toshiaki Toshima Department of Surgery, Kagawa Rosai Hospital Tsuyoshi Ohtani Department of Surgery, Saiseikai Okayama Hospital Ryosuke Yoshida Department of Surgery, Okayama Rosai Hospital Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Hospital Setouchi Colorectal Neoplasm Registration study group collaborators Aim: The oncological benefit of D3 lymph node dissection (D3 LND) for colon cancer in patients aged ≥90 years remains unclear. This study aimed to evaluate the impact of D3 LND on outcomes in this specific, vulnerable population. Method: This retrospective cohort study evaluated 166 patients aged ≥90 years with pathological Stages II–III colon cancer undergoing non-D3 or D3 LND from a multicentre database (2011–2022). Postoperative complications, overall survival and cancer-specific survival were compared between LND groups using propensity score-weighted analyses. Results: D3 LND group had significantly more females and laparoscopic procedures. Operation time was longer, and blood loss was lower in the D3 LND group. Postoperative complications and severe complications were significantly fewer, and postoperative hospital stay was shorter in the D3 LND group. The number of harvested lymph nodes and distal margin was significantly higher in the D3 group. While unadjusted analysis showed better overall survival with D3 LND (p < 0.001), adjusted cancer-specific survival showed no significant difference (p = 0.10). Adjusted mortality risk was significantly higher in the non-D3 group (p = 0.001). Conclusion: In nonagenarian colon cancer patients, D3 LND is safe and feasible without increasing complications, but lacks survival benefit. Careful consideration is warranted, and high-quality D2 LND must be consistently ensured when limited surgery is chosen. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1435-2451 411 1 2025 Surgical outcomes and patient selection in nonagenarians with colon cancer: a comparative multi-institutional study of laparoscopic and open approaches 21 EN Ryohei Shoji 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 Satoe Takanaga Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Ryo Inada Department of Surgery, Kochi Health Sciences Center Toshiaki Toshima Department of Surgery, Kagawa Rosai Hospital Tsuyoshi Ohtani Department of Surgery, Saiseikai Okayama Hospital Ryosuke Yoshida Department of Surgery, Okayama Rosai Hospital Naoto Hori Department of Surgery, Tottori Municipal Hospital Kaoru Shigemitsu Department of Surgery, Tsuyama Chuo Hospital Sumiharu Yamamoto Department of Surgery, Okayama City Hospital Tetsushi Kubota Department of Surgery, Kobe Red Cross Hospital Yuka Okano Department of Surgery, Onomichi City Hospital Tetsuji Nobuhisa Department of Surgery, Himeji Red Cross Hospital Fumitaka Taniguchi Department of Surgery, National Hospital Organization Iwakuni Clinical Center Wataru Ishikawa Department of Surgery, Fukuyama City Hospital Tatsuo Matsuda Department of Surgery, Matsuda Hospital Tatsuo Umeoka Department of Surgery, Matsuyama City Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Setouchi Colorectal Neoplasm Registration study group collaborators Purpose The appropriate surgical approach for colon cancer (CC) in nonagenarian patients remains a subject of clinical debate. This study aimed to compare the short-term outcomes of laparoscopic (Lap) versus open (Open) surgery in patients aged ≥ 90 years with resectable colon cancer. Methods This multi-institutional retrospective cohort study included oldest-old patientswith pathological Stage II/III CC who underwent elective surgery at 15 hospitals between 2011 and 2022. Patients with rectal cancer, Stage 0/I/IV disease, or emergency surgery were excluded. To address selection bias, inverse-probability-weighted regression adjustment and stabilized inverse probability of treatment weighting (sIPTW) were applied. The primary outcome was postoperative complications; secondary outcomes included overall survival (OS). Results Median age was 92 years in both groups. Before adjustment, the Lap group had a higher proportion of female patients (p = 0.038) and lower ASA scores (p = 0.01). Laparoscopic surgery was associated with a significantly longer operative time (220 vs. 171 min, p = 0.046) but less intraoperative blood loss (10 vs. 78 mL, p < 0.01). Postoperative complication rates were comparable (Lap: 31.8%, Open: 33.8%), while the Lap group had a significantly shorter hospital stay (13 vs. 17 days, p < 0.01). D3 lymph node dissection was more frequently performed in the Lap group (p < 0.01). After sIPTW, overall survival did not differ significantly between groups (p = 0.61). Conclusion Both laparoscopic and open surgery are feasible options for selected nonagenarians with colon cancer. Laparoscopic surgery may offer benefits in terms of reduced blood loss and shorter hospitalization, despite longer operative times. Careful patient selection considering frailty and comorbidities is essential in determining the most appropriate surgical approach. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2038-131X 2025 Early C-reactive protein as a predictive biomarker for postoperative complications following robot-assisted surgery for rectal cancer EN Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryusei Takahashi Department of Surgery, NHO Fukuyama Medical Center Hiroki Okabayashi Department of Surgery, NHO Fukuyama Medical Center Masashi Utsumi Department of Surgery, NHO Fukuyama Medical Center Hideaki Miyaso Department of Surgery, NHO Fukuyama Medical Center Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Masaru Inagaki Department of Surgery, NHO Fukuyama Medical Center This retrospective cohort study aimed to assess the predictive value of early postoperative C-reactive protein (CRP) levels for complications following robot-assisted rectal surgery (RARS) for rectal cancer. We analyzed data from 117 consecutive patients who underwent elective RARS at Okayama University Hospital between September 2020 and January 2025. Serum CRP levels were routinely measured preoperatively and on postoperative days (POD) 1 and 4. The primary outcome was the occurrence of any postoperative complication within 30 days, classified according to the Clavien–Dindo grading system. Postoperative complications were observed in 26 patients, representing 22.2% of the cohort. Univariate analysis revealed that several factors were significantly associated with complications, including older age, higher ASA score, neoadjuvant therapy, stoma creation, prolonged operative time, and elevated CRP levels on POD1 and POD4. Notably, multivariate logistic regression analysis identified POD1 CRP as a robust independent predictor of overall postoperative complications (adjusted odds ratio 0.77, 95% confidence interval (CI) [0.63–0.93], p < 0.01). In the ROC analysis, the AUC was 0.735 (bootstrap bias-corrected 95% CI 0.544–0.848). The optimal cutoff value of POD1 CRP was 5.63 mg/dl, at which Youden’s index, yielding a sensitivity of 0.615 and specificity of 0.868. In conclusion, early postoperative measurement of CRP on POD1 serves as a valuable and independent biomarker for predicting complications following RARS for rectal cancer. Incorporating POD1 CRP into postoperative surveillance may facilitate the early identification of high-risk patients, thereby facilitating timely interventions and ultimately improving surgical outcomes in this patient population. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Comparative efficacy of immune checkpoint inhibitor combination therapies by metastatic site in metastatic renal cell carcinoma 3303 EN Shingo Toyoda Department of Urology, Faculty of Medicine, Kindai University Lan Inoki Department of Urology, Faculty of Medicine, Kindai University Mamoru Hashimoto Department of Urology, Faculty of Medicine, Kindai University Wataru Fukuokaya Department of Urology, The Jikei University School of Medicine Keiichiro Mori Department of Urology, The Jikei University School of Medicine Shingo Nishimura Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ryoichi Maenosono Department of Urology, Osaka Medical and Pharmaceutical University Takehiro Iwata Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kensuke Bekku Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takuhisa Nukaya Department of Urology, Fujita-Health University School of Medicine Takafumi Yanagisawa Department of Urology, The Jikei University School of Medicine Takuya Tsujino Department of Urology, Osaka Medical and Pharmaceutical University Kazumasa Komura Department of Urology, Kawasaki University School of Medicine Kiyoshi Takahara Department of Urology, Fujita-Health University School of Medicine Teruo Inamoto Department of Urology, Hamamatsu University School of Medicine Haruhito Azuma Department of Urology, Osaka Medical and Pharmaceutical University Kazutoshi Fujita Department of Urology, Faculty of Medicine, Kindai University JK-FOOT study group Few studies have investigated the efficacy of immuno-oncology (IO) combinations at different metastatic sites in renal cell carcinoma (RCC). We evaluated the differential efficacy of IO–IO and IO–tyrosine kinase inhibitor (TKI) combinations by metastatic site in metastatic RCC (mRCC). This retrospective multicenter study by the JK-FOOT Study Group included 579 patients with intermediate- or poor-risk mRCC (per International Metastatic RCC Database Consortium criteria) treated with first-line IO combinations between September 2018 and December 2024. Metastatic sites were lymph nodes, lungs, bones, liver, brain, and others. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoint was objective response rate. Efficacy was compared between IO–IO and IO–TKI for each site. For lymph node (n = 36), lung (n = 132), or brain (n = 16) metastases, OS or PFS was not significantly different between IO–IO and IO–TKI. In bone metastases (n = 80), OS tended to favor IO–TKI (P = 0.053). In liver metastases (n = 22), OS was significantly longer with IO–TKI (P = 0.011). IO–TKI may be a more appropriate first-line option than IO–IO for mRCC with bone or liver metastases, while efficacy is similar for other sites. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0964-2633 70 3 2025 Prevalence and Modifiable Risk Factors of Dementia in People With Down Syndrome: Cross‐Sectional Study of Japan in Collaboration With the Intellectual Diversity for Goodness Research Consortium (INDIGO‐2019) 329 336 EN Shintaro Takenoshita Department of Neuropsychiatry, Okayama University Hospital Seishi Terada Department of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomokazu Inoue Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Taku Kurozumi Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Manabu Takaki Department of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryozo Kuwano Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Shigeru Suemitsu Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Background: People with Down syndrome (DS) have a strong genetic predisposition to Alzheimer's disease (AD). However, the clinical burden and associated risk factors in diverse, non-Western populations remain less understood. This study aimed to investigate the prevalence of dementia in Japanese adults with DS and to identify modifiable clinical factors associated with dementia. Methods: This cross-sectional multicentre study surveyed 133 adults with DS (mean age 50.1 years) residing in 45 welfare facilities across Japan in 2019. Dementia was diagnosed by a consensus panel of physicians using established criteria (DSM-5, ICD-10, DC-LD) after comprehensive assessments, including the Japanese version of the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID-J). Logistic regression analysis was performed to identify factors independently associated with dementia. Results: Forty-six participants (34.6%) were diagnosed with dementia. The prevalence rose sharply with age: 0% in their 30s, 30.8% in their 40s, 31.6% in their 50s and 65.5% in their 60s. After adjusting for covariates, older age, female sex, dyslipidaemia and visual impairment were independently associated with dementia. Conclusions: This study, the largest of its kind in Asia, confirms a high prevalence of dementia in institutionalized Japanese adults with DS. Crucially, this study is the first to identify dyslipidaemia and visual impairment as independent and potentially modifiable risk factors in this population. These findings highlight tangible targets for clinical interventions aimed at mitigating dementia risk in people with DS. No potential conflict of interest relevant to this article was reported.

eLife Sciences Publications, Ltd Acta Medica Okayama 2050-084X 13 2025 Stimulatory and inhibitory G-protein signaling relays drive cAMP accumulation for timely metamorphosis in the chordate Ciona RP99825 EN Akiko Hozumi Shimoda Marine Research Center, University of Tsukuba Nozomu M Totsuka Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University Arata Onodera Shimoda Marine Research Center, University of Tsukuba Yanbin Wang Shimoda Marine Research Center, University of Tsukuba Mayuko Hamada Ushimado Marine Institute, Okayama University Akira Shiraishi Bioorganic Research Institute, Suntory Foundation for Life Sciences Honoo Satake Bioorganic Research Institute, Suntory Foundation for Life Sciences Takeo Horie Laboratory for Single-cell Neurobiology, Graduate School of Frontier Biosciences, Osaka University Kohji Hotta Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University Yasunori Sasakura Shimoda Marine Research Center, University of Tsukuba Larvae of the ascidian Ciona initiate metamorphosis tens of minutes after adhesion to a substratum via their adhesive organ. The gap between adhesion and metamorphosis initiation is suggested to ensure the rigidity of adhesion, allowing Ciona to maintain settlement after losing locomotive activity through metamorphosis. The mechanism producing the gap is unknown. Here, by combining gene functional analyses, pharmacological analyses, and live imaging, we propose that the gap represents the time required for sufficient cyclic adenosine monophosphate (cAMP) accumulation to trigger metamorphosis. Not only the Gs pathway but also the Gi and Gq pathways are involved in the initiation of metamorphosis in the downstream signaling cascade of the neurotransmitter GABA, the known initiator of Ciona metamorphosis. The mutual crosstalk of stimulatory and inhibitory G-proteins functions as the accelerator and brake for cAMP production, ensuring the faithful initiation of metamorphosis at an appropriate time and in the right situation. No potential conflict of interest relevant to this article was reported.

岡山大学文学部学芸員課程 Acta Medica Okayama 20 2025 学芸員課程 Newsletter 第20号 EN 10.18926/70233 No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2261 25 1 2025 Prognostic value of right atrial strain in patients with chronic heart failure 908 EN Rie Nakayama Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Yoichi Takaya Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Mitsutaka Nakashima Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Takahiro Nishihara Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Norihisa Toh Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Miyoshi Toru Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Kazufumi Nakamura Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Shinsuke Yuasa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Aims Right ventricular dysfunction is a well-established prognostic marker in patients with heart failure (HF). However, the prognostic significance of right atrial (RA) function remains unclear. Given its sensitivity to systemic congestion, RA function may provide additional insights into HF disease progression and management. This study aimed to investigate whether RA reservoir function serves as an independent prognostic indicator in patients with chronic HF. Methods A total of 613 patients with chronic HF and a left ventricular (LV) ejection fraction of less than 50% who underwent echocardiographic assessment at Okayama University Hospital between January 2018 and March 2023 were included (median age: 68 (58–76) years; 69% male). RA reservoir function was quantified using two-dimensional speckle-tracking echocardiography. The primary endpoint was cardiovascular death or HF-related hospitalization. Kaplan–Meier survival analysis was performed to examine the association between RA reservoir function and clinical outcomes. Results During a median follow-up period of 41 months (range: 12–91 months), 119 patients experienced cardiac events. Compared with event-free patients, those with cardiac events exhibited a significantly larger RA maximum volume index (38 mL/m2 vs. 31 mL/m2, P < 0.001) and a significantly lower RA reservoir longitudinal strain (RASr) (17% vs. 22%, P < 0.001). Kaplan–Meier analysis demonstrated that patients with RASr ≤ 20% had significantly poorer event-free survival than those with RASr > 20%, even without RA volume enlargement (log-rank test, P < 0.001). Multivariate Cox regression analysis identified RASr as an independent predictor of cardiac events (hazard ratio: 0.95, 95% confidence interval: 0.93 to 0.97, P < 0.001). Conclusions In patients who experienced adverse cardiac events, a reduced RASr and an increased RA maximum volume were observed. Furthermore, a reduced RASr was independently associated with an increased risk of cardiovascular death and HF-related hospitalization in patients with chronic HF and LV dysfunction. These findings indicate that RASr may serve as a valuable prognostic marker for the risk stratification and management of chronic HF. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1613-6810 21 50 2025 Collagen Signaling via DDR1 Exacerbates Barriers to Macromolecular Drug Delivery in a 3D Model of Pancreatic Cancer Fibrosis e06926 EN Mayu Ohira Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Moe Kitamura Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyo Iwasaki Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haruko Ohta‐Okano Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiyori Tsujii Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Reika Nakamura Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuya Nakazawa Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Akihiro Nishiguchi Biomaterials Field, Research Center for Macromolecules and Biomaterials, National Institute for Materials Science Masaya Yamamoto Department of Materials Processing, Graduate School of Engineering, Tohoku University Kensuke Osada Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Sciences and Technology (QST) Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Horacio Cabral Department of Bioengineering, Graduate School of Engineering, The University of Tokyo Atsushi Masamune Division of Gastroenterology, Graduate School of Medicine, Tohoku University Mitsunobu R. Kano Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Hiroyoshi Y. Tanaka Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fibrosis is a significant barrier to drug delivery in pancreatic ductal adenocarcinoma (PDAC) and contributes to its dismal prognosis. Pancreatic stellate cells (PSCs) drive fibrosis by excessively secreting extracellular matrix proteins such as collagen I. Collagen I is thought to physically obstruct the delivery of macromolecules, such as albumin, antibodies, and nanomedicines. Apart from its structural role, collagen signals through dedicated cell surface receptors, such as the discoidin domain receptors (DDR) 1/2. However, whether and how collagen signaling contributes to fibrotic barrier generation remains uncharacterized. Here, a 3D culture model of PDAC fibrosis constructed from patient PSCs is used to assess the contribution of DDR1/2-mediated collagen signaling. DDR1/2 inhibition diminishes collagen I expression in PSCs to enhance macromolecular delivery. Moreover, MEK inhibitors exacerbate the fibrotic barrier by up-regulating collagen I, an effect reversed by inhibiting DDR1/2. Through isoform-specific targeting, inhibiting DDR1, but not DDR2, is shown to be effective. Downstream of DDR, the involvement of the PI3K/AKT/mTOR pathway is demonstrated, particularly alternative mTOR complexes involving MEAK7 and GIT1. Altogether, the results show in vitro that DDR1-mediated collagen signaling exacerbates the fibrotic barrier and may be targeted to enhance macromolecular drug delivery in PDAC. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1546-0096 23 1 2025 Comparison of clinical practices during the transitional and young adult phases between patients with oligoarticular/polyarticular juvenile idiopathic arthritis and those with rheumatoid arthritis in Japan 120 EN Sho Mori Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine Kosuke Shabana Department of Pediatrics, Osaka Medical and Pharmaceutical University Toshihiro Matsui Department of Rheumatology Research, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital Tomo Nozawa Department of Pediatrics, Graduate School of Medicine, Yokohama City University Yuko Sugita Department of Pediatrics, Osaka Medical and Pharmaceutical University Minako Tomiita Department of Allergy and Rheumatology, Chiba Children’s Hospital Yasuo Nakagishi Department of Pediatric Rheumatology, Hyogo Prefectural Kobe Children’s Hospital Yuichi Yamasaki Department of Pediatrics, Kagoshima University Hospital Hiroaki Umebayashi Department of General Pediatrics, Miyagi Children’s Hospital Masato Yashiro Department of Pediatrics, Okayama University Hospital Naomi Iwata Department of Infection and Immunology, Allergy and Immunology Center, Aichi Children’s Health and Medical Center Junko Yasumura Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences Hiroyuki Wakiguchi Department of Pediatrics, Yamaguchi University Graduate School of Medicine Takeshi Yamamoto Department of Pediatrics, Chiba University Graduate School of Medicine Shunichiro Takezaki Department of Pediatrics, Faculty of Medicinea and Graduate School of Medicine, Hokkaido University Yuka Okura Center for Pediatric Allergy and Rheumatology, KKR Sapporo Medical Center Tadafumi Yokoyama Department of Pediatrics, Kanazawa University Masaki Shimizu Department of Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Masahiro Hirayama Department of Pediatrics, Mie University Graduate School of Medicine Shigeto Tohma Department of Rheumatology, National Hospital Organization Tokyo National Hospital Nami Okamoto Department of Pediatrics, Osaka Medical and Pharmaceutical University Masaaki Mori Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine Background Juvenile idiopathic arthritis (JIA) is a chronic inflammatory condition that frequently persists into adulthood, posing long-term challenges in disease control and quality of life. However, clinical management during the transitional and young adult phases remains insufficiently characterized, especially in comparison with adult-onset rheumatoid arthritis (RA). This study aimed to compare disease activity, medication use, and treatment practices between patients with oligoarticular/polyarticular JIA and those with RA, focusing on individuals aged 16–30 years. Methods Data were derived from two nationwide multicenter databases in Japan—NinJa (National Database of Rheumatic Diseases in Japan) for RA and CoNinJa (a pediatric counterpart of NinJa) for JIA. A total of 176 JIA and 152 RA patients, all aged 16–30 years, were analyzed. Clinical parameters, disease activity indices, and medication profiles were compared using the Mann–Whitney U test and Fisher’s exact test. Results Compared to RA patients, JIA patients demonstrated significantly lower disease activity (median SDAI 0.6 vs. 2.4) and higher remission rates, particularly Boolean remission (70% vs. 44%) (p < 0.001). MTX usage was less frequent in JIA (49% vs. 68%, p < 0.001), whereas biologic use was notably more common (69% vs. 38%, p < 0.001), with 31% involving off-label prescriptions. Among patients in CDAI remission, biologic monotherapy was observed more frequently in JIA (29% vs. 7%, p < 0.001). Discontinuation of MTX was most commonly attributed to disease improvement (58%) or gastrointestinal intolerance (nausea, 29%). Subcutaneous tocilizumab, though unapproved for JIA in Japan, had the lowest discontinuation rate (4%), suggesting favorable tolerability. Conclusions Despite an overlap in age, patients with JIA and RA exhibit distinct disease characteristics and therapeutic patterns. These differences underscore the need to expand approved treatment options for JIA, promote equitable access to biologics, and strengthen transitional care frameworks. Further research is warranted to explore long-term outcomes, reproductive health considerations, and socioeconomic barriers that influence treatment continuity in young adults with childhood-onset arthritis. No potential conflict of interest relevant to this article was reported.

American Medical Association (AMA) Acta Medica Okayama 2574-3805 8 11 2025 Trastuzumab Deruxtecan for ERBB2-Mutant Metastatic Non–Small Cell Lung Cancer With or Without Brain Metastases: A Secondary Analysis of Randomized Clinical Trials e2543107 EN Pasi A. Jänne Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute David Planchard Department of Medical Oncology, Thoracic Cancer Group, Gustave Roussy, Medical Oncology Koichi Goto Department of Thoracic Oncology, Nation Cancer Center Hospital East Egbert F. Smit Department of Pulmonary Diseases, Leiden University Medical Center Adrianus Johannes de Langen Department of Thoracic Oncology, Netherlands Cancer Institute Yasushi Goto Department of Thoracic Oncology, National Cancer Center Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Toshio Kubo Center for Clinical Oncology, Okayama University Hospital Maurice Pérol Department of Medical Oncology, Centre Léon Bérard Enriqueta Felip Department of Medical Oncology, Vall d’Hebron University and Vall d’Hebron Institute of Oncology Hidetoshi Hayashi Department of Medical Oncology, Kindai University Faculty of Medicine Kazuhiko Nakagawa Department of Medical Oncology, Kindai University Faculty of Medicine Junichi Shimizu Department of Thoracic Oncology, Aichi Cancer Center Misako Nagasaka Division of Hematology-Oncology, Department of Medicine, University of California Irvine Kaline Pereira Daiichi Sankyo Inc Ayumi Taguchi Daiichi Sankyo Co Ltd Ahmed Ali Daiichi Sankyo Europe GmbH Maha Karnoub Daiichi Sankyo Inc Rie Yonemochi Daiichi Sankyo Inc David Leung Daiichi Sankyo Inc Bob T. Li Thoracic Oncology and Early Drug Development Service, Global Research Program, Memorial Sloan Kettering Cancer Center Importance Brain metastases reduce overall survival rates of patients with non–small cell lung cancer (NSCLC); patients with epidermal growth factor receptor 2 (ERBB2 [formerly HER2])–mutant NSCLC are more likely to have baseline brain metastases. Trastuzumab deruxtecan (T-DXd) is an approved ERBB2-directed treatment for previously treated unresectable or metastatic ERBB2-mutant NSCLC. Objective To assess the clinical effectiveness and safety of T-DXd 5.4 mg/kg and 6.4 mg/kg doses in patients with previously treated ERBB2-mutant metastatic NSCLC with or without untreated or previously treated stable brain metastases. Design, Setting, and Participants This post hoc secondary analysis pooled patients from the DESTINY-Lung01 (data cutoff date: December 3, 2021) and DESTINY-Lung02 (data cutoff date: December 23, 2022) clinical trials by T-DXd dose (5.4 mg/kg and 6.4 mg/kg). DESTINY-Lung01 was a multicenter, open-label, 2-cohort, nonrandomized phase 2 study, while DESTINY-Lung02 was a dose-blinded, multicenter, 2-cohort, randomized phase 2 study. Participants had a previously treated ERBB2-mutant metastatic NSCLC with or without untreated or previously treated stable brain metastases at baseline. All statistical analyses were performed from April 2023 to October 2024. Intervention Patients received a T-DXd dose of either 5.4 mg/kg or 6.4 mg/kg intravenously every 3 weeks. Main Outcome and Measure Systemic and intracranial effectiveness by blinded independent central review using RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1, sites of progression, and safety. Results This analysis included 102 patients in the T-DXd 5.4-mg/kg dose group (65 females [64%]; median [range] age, 57.5 [37.0-83.0] years and 59.5 [30.0-79.0] years in patients with and without brain metastases, respectively) and 141 patients in the T-DXd 6.4-mg/kg dose group (94 females [67%]; median [range] age, 62.5 [29.0-88.0] years and 59.0 [27.0-83.0] years in patients with and without brain metastases, respectively). In each group, 31% (32 of 102) and 38% (54 of 141) of patients, respectively, had baseline brain metastases and 53% (17 of 32) and 44% (24 of 54), respectively, received prior brain metastasis treatment. In patients with and without brain metastases, systemic confirmed objective response rates (ORRs) were 47% (15 of 32; 95% CI, 29%-65%) and 50% (35 of 70; 95% CI, 38%-62%), respectively, with the T-DXd 5.4-mg/kg dose, and 50% (27 of 54; 95% CI, 36%-64%) and 59% (51 of 87; 95% CI, 48%-69%) with the T-DXd 6.4-mg/kg dose. Median progression-free survival was 7.1 (95% CI, 5.5-9.7) months in the T-DXd 5.4-mg/kg dose group and 7.1 (95% CI, 4.5-9.6) months in the T-DXd 6.4-mg/kg dose group of patients with baseline brain metastases. Among patients with measurable baseline brain metastases, intracranial confirmed ORRs were 50% (7 of 14; 95% CI, 23%-77%) with the T-DXd 5.4-mg/kg dose and 30% (9 of 30; 95% CI, 15%-49%) with the T-DXd 6.4-mg/kg dose. At both doses, the safety profile of T-DXd was generally manageable, regardless of baseline brain metastases, favoring the T-DXd 5.4 mg/kg dose. Conclusions and Relevance In this secondary analysis, T-DXd at the approved dose of 5.4 mg/kg showed antitumor activity in patients with previously treated ERBB2-mutant metastatic NSCLC with or without brain metastases. This finding supports T-DXd 5.4 mg/kg use in this population. No potential conflict of interest relevant to this article was reported.

岡山大学文学部 Acta Medica Okayama 0285-4864 78 2025 裏表紙・英文目次 EN No potential conflict of interest relevant to this article was reported.

岡山大学文学部 Acta Medica Okayama 0285-4864 78 2025 「有翼の天女図」十二考 ─ 和田英作による帝国劇場観覧席の天井画とその周辺 ─ 100 80 EN Yuko TATSUNO 10.18926/okadai-bun-kiyou/70222 No potential conflict of interest relevant to this article was reported.

岡山大学文学部 Acta Medica Okayama 0285-4864 78 2025 文学部教員研究活動一覧（2024年度） 63 77 EN No potential conflict of interest relevant to this article was reported.

岡山大学文学部 Acta Medica Okayama 0285-4864 78 2025 可能表現としての「可能だ」「不可能だ」 51 62 EN Kazuhito MIYAZAKI 10.18926/okadai-bun-kiyou/70220 No potential conflict of interest relevant to this article was reported.

岡山大学文学部 Acta Medica Okayama 0285-4864 78 2025 広島市方言におけるアクセントの継承と変容（1）─ 1 拍・2 拍・3 拍名詞のアクセントの世代的動態 ─ 39 50 EN Yasue NAKATO 10.18926/okadai-bun-kiyou/70219 No potential conflict of interest relevant to this article was reported.

岡山大学文学部 Acta Medica Okayama 0285-4864 78 2025 ビザンツ支配、セルジューク朝侵入、そして十字軍到来の狭間で ─ アルメニア語史料『アブドルムセフとその子孫たちの歴史』訳註（2） 29 37 EN Kosuke NAKADA 10.18926/okadai-bun-kiyou/70218 No potential conflict of interest relevant to this article was reported.

岡山大学文学部 Acta Medica Okayama 0285-4864 78 2025 戦後80周年の英国の対日戦勝記念日（VJ デイ）の催しおよびドイツ・ベルリンの企画展 13 28 EN Tomoyo NAKAO 10.18926/okadai-bun-kiyou/70217 No potential conflict of interest relevant to this article was reported.

岡山大学文学部 Acta Medica Okayama 0285-4864 78 2025 非大都市圏小規模自治体の持続的発展と地域的対応の特徴 1 11 EN Hirofumi KITAGAWA 10.18926/okadai-bun-kiyou/70216 No potential conflict of interest relevant to this article was reported.

岡山大学文学部 Acta Medica Okayama 0285-4864 78 2025 表紙・目次 EN No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 0309-0167 88 5 2025 Claudin-18 expression in gastric type adenocarcinoma and HPV-associated adenocarcinoma of the uterine cervix 1003 1015 EN Nobuko Yasutake Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Yuki Yokawa Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Takehiro Tanaka Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Riri Mishima Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Misato Komamizu Department of Gynecology and Obstetrics, Graduate School of Medical Sciences Kyushu University Fukuoka Japan Ryosuke Kuga Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University Rina Jiromaru Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University Shinichiro Kawatoko Department of Medicine and Clinical Science, Kyushu University Beppu Hospital Kenzo Sonoda Department of Gynecology, Kyushu University Beppu Hospital Hideaki Yahata Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Kiyoko Kato Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Yoshinao Oda Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University Hidetaka Yamamoto Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Aims: Claudin-18 (CLDN18) is both a marker for the gastric phenotype and a therapeutic target. However, little is known about its immunoexpression in endocervical adenocarcinomas (ECAs), particularly as detected using the clone 43-14A antibody, or about the gene expression of its isoforms in ECAs. Methods and results: We examined CLDN18, HIK1083, p16 and Rb expression by immunohistochemistry and high-risk human papillomavirus (HR-HPV) mRNA by in situ hybridization (ISH) in 121 ECAs, including 35 HPV-independent adenocarcinomas (gastric type [GAS], n = 24; non-GAS, n = 11) and 86 HPV-associated ECAs. We also analysed mRNA expression of the CLDN18.1 (lung type) and CLDN18.2 (gastric type) isoforms by quantitative polymerase chain reaction (qPCR) in selected cases. CLDN18 positivity was detected in 8/24 (33%) GASs, 0/11 (0%) non-GASs and 2/86 (2%) HPV-associated ECAs, with positivity defined as staining in ≥75% of tumour cells, as in gastric cancer. When a 5% cut-off was used, CLDN18 positivity was detected in 22/24 (92%) GASs, 0/11 (0%) non-GASs and 6/86 (7%) HPV-associated ECAs; CLDN18 expression was thus significantly associated with GAS histology (P < 0.0001). Among the 6 cases of HPV-associated ECAs with CLDN18 expression (ranging from 5% to 80%), the histological patterns included a mix of usual and mucinous features in 4 cases, pure usual type in 1 and villoglandular variant in 1. Otherwise features such as p16 overexpression and the Rb partial loss pattern were consistent with those of HPV-associated ECAs. Six of 22 (27%) CLDN18-positive GASs were also positive for p16, but their other features—such as CLDN18 expression and the Rb preserved pattern—were the same as in p16 negative GASs. Expression of CLDN18.2 mRNA but not CLDN18.1 mRNA was confirmed in both GASs and HPV-associated ECAs. Conclusions: CLDN18 (43-14A) emerged as a potential diagnostic and therapeutic marker for GAS. A minor subset of HPV-associated ECAs also can be immunoreactive for CLDN18 and express CLDN18.2 mRNA, suggesting divergent gastric phenotypic differentiation. The caution is that GAS and HPV-associated ECAs can share overlapping histological features and similar expression of CLDN18 and p16. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 7 2025 The Challenge of Diagnosing Scirrhous Gastric Cancer by Endoscopic Biopsy: A Case Report e87334 EN Yuka Ikeda Department of Internal Medicine, Clinic IkedaDepartment of Internal Medicine, Clinic Ikeda Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tadashi Yoshino Department of Pathology, Okayama University Takehiro Tanaka Department of Pathology, Okayama University Hospital Nobumasa Ikeda Department of Internal Medicine, Clinic Ikeda Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Scirrhous gastric cancer, also known as linitis plastica, is a rare and aggressive subtype of gastric carcinoma that poses significant diagnostic challenges due to its submucosal infiltration and often normal-appearing mucosa. We report a case involving a 30-year-old Japanese woman who presented with a six-month history of epigastric pain and postprandial vomiting. Initial endoscopic examination revealed erythema and mucosal swelling, with limited antral distensibility and resistance during duodenal intubation. Despite 12 mucosal biopsies, histopathological examination revealed no evidence of malignancy. Given the strong clinical and endoscopic suspicion of scirrhous gastric cancer, additional deep sections and immunohistochemical staining were performed. These revealed scattered signet-ring cell carcinoma and poorly differentiated adenocarcinoma, with positive immunostaining for p53 and Ki67. The patient underwent total gastrectomy, and the diagnosis of scirrhous gastric cancer was confirmed on the resected specimen. This case highlights the importance of a high index of clinical suspicion, close collaboration between endoscopists and pathologists, and the utility of ancillary diagnostic tools, such as immunohistochemistry, in identifying subepithelial gastric malignancies that may be missed on conventional biopsy. No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 191 2026 地域と人々を繋ぐ音楽活動 ― 地域活力の回復を目指すコンサートの開催 ― 131 145 EN Shinsuke OKAMOTO Faculty of Education, Okayama University 10.18926/bgeou/70202 　本研究は，人口減少に伴って小中学校の統廃合が進む岡山県玉野市において，地域活力の回復を図る機会を作り，そのような機会を地域住民自ら作り出す機運を高めることを目的としている。本研究では，東児中学校区を対象に，校歌を再構成した作品の発表と，地域住民と協働で企画，運営を行うコンサートの開催という二つの取組を2023～24年度にかけて実践し，住民同士の繋がりを強め，住民らが地域への関心を深めていくことを図った。両取組は，地域住民に好意的に受け入れられた結果となり，今後の取組の展開へ繋がる成果が得られた。2025年現在，両取組を実践した地域において，地域活性化を図る芸術活動団体が新たに結成され，地域活力の回復を目指す動きが住民の中で見られはじめていることから，本地域の今後の動向が注目される。 No potential conflict of interest relevant to this article was reported.

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

Japan Society of Mechanical Engineers Acta Medica Okayama 2187-9745 12 5 2025 Examining OpenFOAM-based LES analysis in terms of inviscid energy conservation and viscous turbulence decay 25-00095 EN Hiroki SUZUKI Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kento TANAKA Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Toshinori KOUCHI Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The present study examines an OpenFOAM-based LES analysis from the viewpoints of inviscid energy conservation and viscous turbulence decay. The Smagorinsky model is employed as the sub-grid scale (SGS) model, and a two-dimensional periodic analytical solution and a three-dimensional periodic Taylor-Green vortex (TGV) are employed to represent inviscid flows. The analytical relationship for the kinetic energy K, dK/dt = 0, with t as the dimensionless time, is utilized to validate the OpenFOAM results. For the viscous flow case, the TGV flow in a three-dimensional periodic cubic domain is adopted, and its turbulence kinetic energy distribution is compared with that obtained by a spectral method to examine the analysis. The OpenFOAM-based analysis exhibits energy conservation error in flows that should ideally conserve energy. For the two-dimensional flow, this error decreases with increasing grid resolution N. However, in the three-dimensional flow, the error does not improve even with higher N. In the three-dimensional TGV flow, the turbulence kinetic energy predicted by OpenFOAM exhibits a strong agreement with that from the spectral method when a standard constant value of the Smagorinsky model is employed and the mesh is sufficiently refined. Conversely, for a condition of relatively coarse mesh, the decay characteristics of turbulent kinetic energy deviate from those of the spectral method, and a higher constant value of the Smagorinsky model than the default value becomes necessary to reproduce comparable results. These results suggests that even in LES simulations where highly accurate conservation laws are not satisfied, adjusting the model constants so that the predicted values match experimental or numerical reference data can improve the apparent reliability of the turbulent kinetic energy in the decaying turbulence. No potential conflict of interest relevant to this article was reported.

The Carbon Society of Japan Acta Medica Okayama 2436-5831 4 3 2025 Synthesis and applications of porous carbonaceous materials with inherited molecular structural features from the precursor molecules 179 187 EN Koki Chida Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Takeharu Yoshi Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Kazuhide Kamiya Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka Ryota Sakamoto Department of Chemistry, Graduate School of Science, Tohoku University Fumito Tani Institute for Materials Chemistry and Engineering, Kyushu University Tomoki Ogoshi Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University Hirotomo Nishihara Institute of Multidisciplinary Research for Advanced Materials, Tohoku University The carbonization of organic crystalline materials, such as metal organic frameworks and covalent organic frameworks, has emerged as a promising approach for producing functional porous carbonaceous materials. However, both the chemically defined long-term ordered structures and the local chemical structures derived from these precursor materials are generally lost, resulting in amorphous carbons. As a result, controlling the molecular-level structure of nanoporous carbons remains a significant challenge. We report a new bottom-up synthesis approach for porous carbons with a molecular-level design, involving the carbonization of well-designed precursor molecules by thermal polymerization. Among the resulting carbons, ordered carbonaceous frameworks, which contain a high-density of regularly aligned single-atomic metal species, have been identified as promising platforms for single-atom catalysts. This approach also enables the synthesis of various three-dimensional porous carbons that reflect the structural features of their precursor molecules. Recent progress in the synthesis and applications of porous carbons derived from molecular precursors is summarized, highlighting their potential for the development of functional materials. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2590-1397 28 2025 Flow diverter treatment for internal carotid artery aneurysm following management of distal cerebral aneurysms: Technical note 100540 EN Yuichi Hirata Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Hiramatsu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Sugiu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fukiko Baba Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Juntaro Fujita Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Sotome Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masato Kawakami Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryu Kimura Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Ebisudani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Haruma Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohito Hishikawa Department of Neurosurgery, Kawasaki Medical School Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: In recent years, the effectiveness of flow diverters (FDs) for the treatment of intracranial aneurysms has been reported. While FDs are effective, their deployment involves advancing a delivery wire distally, which may pose a risk if a distal aneurysm exists within the same artery. In such cases, the delivery wire could potentially perforate the distal aneurysm. Here, we present two cases of tandem aneurysms in which an internal carotid artery (ICA) aneurysm was treated with an FD following the treatment of a distal cerebral aneurysm. Case description: A 44-year-old woman and a 67-year-old woman underwent magnetic resonance imaging for headache or abducens nerve palsy. In both cases, two aneurysms were revealed: one at the ICA and the other either at the middle cerebral artery or the top of the ICA. Due to the risk of perforation by the delivery wire during FD deployment, the distal aneurysms were treated first—either with surgical neck clipping or stent-assisted coil embolization. One month after the initial treatment, FD placement for the ICA aneurysm was performed as planned without complications in either case. Discussion: This is the first report where tandem aneurysms were successfully treated with treatment for distal cerebral aneurysms, followed by FDs for proximal ICA aneurysms. We emphasize the potential risk of perforation of the distal aneurysm by the delivery wire during FD placement. Conclusion: Treatment of distal cerebral aneurysms beforehand can help ensure the safe and effective use of FDs in patients with tandem aneurysms. No potential conflict of interest relevant to this article was reported.

Japan Stroke Society Acta Medica Okayama 0912-0726 47 6 2025 頭蓋頚椎移行部動静脈瘻の開頭手術時における上腕動脈穿刺による脳血管撮影の有用性 410 412 EN Yuichi Hirata Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Hiramatsu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Sasada Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Juntaro Fujita Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Sotome Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masato Kawakami Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryu Kimura Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Ebisudani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kyohei Kin Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Haruma Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Sugiu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shota Tanaka Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 頭蓋頚椎移行部動静脈瘻の手術では，異常血管の確認のため術中血管撮影が重要であるが，体位変換時のsheathの固定や撮影血管へのカテーテルの誘導が困難である．今回，頭蓋頚椎移行部動静脈瘻の開頭手術において上腕動脈穿刺によりultra-long sheathを鎖骨下動脈に留置して椎骨動脈撮影（vertebral artery angiography: VAG）を行う方法の有用性を報告する．当院で本血管撮影を施行した症例の患者背景や合併症を評価した．企図した4例，5血管でVAGを施行でき，合併症も認めなかった．体位変換も腹臥位における穿刺部の観察も簡便であり，カテーテルの操作性にも優れ，VAGを容易に施行することができた．また，管球を頭側から移動する際の術野との干渉も最小限に抑えられた．本方法は利点が多く，有用な血管撮影方法であり，頭蓋頚椎移行部動静脈瘻の手術における一助となり得ると考える． No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0956-7135 183 2026 Monitoring postharvest water loss in eggplants (Solanum melongena L.) using UV-induced fluorescence imaging and multivariate analysis 111902 EN Vincent Rotich Laboratory of Biosensing Engineering, Graduate School of Agriculture, Kyoto University Tianqi Gao Laboratory of Biosensing Engineering, Graduate School of Agriculture, Kyoto University Panintorn Prempree Laboratory of Biosensing Engineering, Graduate School of Agriculture, Kyoto University Takahiro Hayashi Laboratory of Biosensing Engineering, Graduate School of Agriculture, Kyoto University Kazuhiko Namba Faculty of Environmental, Life, Natural Science and Technology, Okayama University Mitsuji Monta Faculty of Environmental, Life, Natural Science and Technology, Okayama University Motomi Nishimoto Technology and Innovation Center, Daikin Industries, Ltd. Naoshi Kondo Laboratory of Biosensing Engineering, Graduate School of Agriculture, Kyoto University Eggplant (Solanum melongena L.) is susceptible to significant postharvest losses primarily due to water loss during storage, which affects market quality by causing texture and glossiness degradation. We investigated whether UV-induced fluorescence imaging and EEM (Excitation-Emission Matrix) fluorescence spectroscopy can non-destructively monitor WL under four storage regimes (10 °C/95 % RH, 20 °C/95 % RH, 20 °C/75 % RH, 10 °C/75 % RH). EEMs exhibited three regions; a 365/420 nm blue emission increased most under warm, low-humidity storage and is consistent with phenolic/lignin-related fluorescence. Side-view fluorescence (FL) images showed progressive blue-white emission and surface textural changes that tracked gravimetric water loss (WL). A PLSR model using combined color and texture features from FL and reflectance (CL) images achieved R2CV = 0.88 (RMSECV = 3.47 %) with only six features. To test a minimal predictor, we fit an Analysis of Covariance (ANCOVA) using Day-1 FL MeanBlue as a covariate and storage category as a factor with Leave One Out Cross-validation (LOOCV); this forecasted cumulative WL with R2LOOCV = 0.92 and MAE = 1.88 %. Importantly, this ANCOVA model using Day-1 blue-band fluorescence as a covariate was predictive only under 20 °C/75 % RH; under the other conditions, its contribution was weak. Linear Discriminant Analysis (LDA) and Support Vector Machine (SVM) models achieved accuracies of 94.4 % and 85.2 %, respectively, in differentiating storage conditions. These results support low-cost FL imaging as a practical tool to monitor WL and storage stress. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0969-0239 32 16 2025 Development of sulfation for cellulose pulp to change its fiber morphology and appearance to transparent in water 9663 9677 EN Ayato Nishimura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tetsuya Uchida Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Cellulose pulp (CP) is composed mainly of cellulose which is one of the most useful and sustainable natural polymers. Cellulose-based materials, such as completely dispersed nanofibers and water-soluble cellulose, are transparent in water. Additionally, chemical modification of CP has been employed as a pretreatment for the preparation of nanofibers and to impart absorption properties derived from anionic functional groups. However, little is known about chemically modified CPs comprising micron-scale fibers that are transparent in water.In this study, we synthesized transparent sulfated cellulose pulp (TSCP) that exhibits good dispersion stability, high transparency in water, and highly swollen fiber structures. The sulfation method involved heating sulfamic acid and urea supported on CP. TSCP synthesized using a sulfamic acid amount relative to CP (Q) of 18.5, a molar ratio of urea to sulfamic acid (R) of 0.80, and a reaction temperature of 140 °C exhibited the highest total light transmittance (94.7%) in water, a degree of polymerization (535), and amount of sulfate groups (1.73 mmol/g). Polarization microscopy confirmed that most TSCP fibers swelled in water along the fiber width direction. The structure of hydrous-state TSCP was further confirmed using low-vacuum scanning electron microscopy. The maximum fiber width of the swollen TSCP reached 122 μm, which was approximately six times than that of CP. The crystallinity was equivalent to that of the original CP with a Cellulose I-type crystalline structure. This transparent, hydrous-state TSCP, comprising predominantly swollen CP fibers, demonstrates potential for applications as a transparent material. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2752-6542 5 1 2025 Chloroplast heat shock protein cpHsc70-1 interacts with thylakoid membrane remodeling protein VIPP1 C-terminal tail and controls VIPP1 oligomer assembly pgaf393 EN Di Li Institute of Plant Science and Resources, Okayama University Sarah Wanjiru Gachie Institute of Plant Science and Resources, Okayama University Shin-ichiro Ozawa Institute of Plant Science and Resources, Okayama University Martin Scholz Institute of Plant Biology and Biotechnology, University of Münster Michael Hippler Institute of Plant Science and Resources, Okayama University Wataru Sakamoto Institute of Plant Science and Resources, Okayama University Oxygenic photosynthetic organisms depend on the thylakoid membranes (TMs) for light-driven energy conversion. Recent studies on TM homeostasis (thylakostasis) have highlighted the essential role of the TM remodeling protein vesicle-inducing protein in plastid 1 (VIPP1). As a member of the endosomal sorting complexes required for transport-III (ESCRT-III)/phage shock protein A (PspA)/VIPP1 superfamily, VIPP1 forms large ring- and filament-like homo-oligomeric structures that exhibit a membrane remodeling activity. The oligomerization status was proposed to be modulated by the intrinsically disordered C-terminal tail (Vc), whereas its functional role remained unclear. Notably, this Vc region is conserved not only in photosynthetic VIPP1 but also in the PspA proteins of extremophilic species, implicating its role in membrane stress responses. To investigate the role of the Vc region in VIPP1 assembly, we performed coimmunoprecipitation assays in Arabidopsis chloroplasts and identified chloroplast-localized HSP70 proteins (cpHsc70) as major interactors. Among the two isoforms, cpHsc70-1 was found to be specifically required for modulating VIPP1 oligomeric assembly and dynamics in response to heat stress. Genetic analyses revealed that cpHsc70-1 facilitates the disassembly of VIPP1 oligomers, similarly to Vps4 ATPase in ESCRT-III; loss of either the Vc region or cpHsc70-1-impaired VIPP1 disassembly, resulting in more static oligomeric structures. Furthermore, cpHsc70-1 exhibited a broader role in chloroplast proteostasis, as the cphsc70-1 mutant showed impaired accumulation of green fluorescent protein (GFP)-fusion proteins. Together, our findings uncover a crucial crosstalk between proteostasis and thylakostasis in chloroplasts, coordinated by cpHsc70-1 and VIPP1 in response to membrane stress. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Calcium ions play a critical role in calcification of Corynebacterium matruchotii 4591 EN Naoko Ohara Department of Operative Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Midori Ogawa Department of Microbiology, School of Medicine, University of Occupational and Environmental Health Katsuki Takebe Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ikue Tosa Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Serina Ono Department of Operative Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mitsumasa Saito Department of Microbiology, School of Medicine, University of Occupational and Environmental Health Naoya Ohara Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Dental calculus is a hardened deposit composed of calcium phosphate precipitated within dental plaque. While the involvement of dental calculus in the progression of periodontal disease is well established, many aspects of its formation process remain poorly understood. In this study, we focused on Corynebacterium matruchotii, a key bacterium involved in dental calculus formation, and investigated the role of calcium ions in calcification, as well as the associated internal and external changes in the bacterium through long-term observation. In the absence of calcium ions, no intracellular calcification was observed, and the lipid bilayer with the formation of holes in bacterial body was evident. In contrast, in the presence of calcium ions, lipid bilayer remained intact, and intracellular needle- and plate- like crystals were formed. Furthermore, calcified C. matruchotii showed increased flocculation compared to non-calcified C. matruchotii. These results indicate that the influx of calcium ions is essential for intracellular calcification. Calcium ions entry appears to reinforce the integrity of the lipid bilayer, providing a stable intracellular environment conductive to calcification. Moreover, calcified C. matruchotii may contribute to the nucleation of dental calculus by forming aggregates composed of both bacterial components and calcified material. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1123-6337 29 1 2025 Safety and feasibility of D3 lymph node dissection in oldest-old patients undergoing colorectal cancer surgery: a multi-institutional, retrospective analysis 146 EN R. Inada Department of Surgery, Kochi Health Sciences Center F. Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences T. Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital S. Takanaga Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences T. Toshima Department of Surgery, Kagawa Rosai Hospital T. Ohtani Department of Surgery, Saiseikai Okayama Hospital R. Yoshida Department of Surgery, Okayama Rosai Hospital N. Hori Department of Surgery, Tottori Municipal Hospital K. Shigemitsu Department of Surgery, Tsuyama Chuo Hospital S. Yamamoto Department of Surgery, Okayama City Hospital T. Kubota Department of Surgery, Kobe Red Cross Hospital Y. Okano Department of Surgery, Onomichi City Hospital T. Nobuhisa Department of Surgery, Himeji Red Cross Hospital F. Taniguchi Department of Surgery, National Hospital Organization Iwakuni Clinical Center W. Ishikawa Department of Surgery, Fukuyama City Hospital R. Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences T. Matsuda Department of Surgery, Matsuda Hospital T. Umeoka Department of Surgery, Matsuyama City Hospital T. Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Setouchi Colorectal Neoplasm Registration Study Group Collaborators Background Colorectal cancer (CRC) is a significant health burden, with lymph node dissection (LND) playing a critical role in staging and guiding treatment. However, the optimal extent of LND for the oldest-old population (aged ≥ 90 years) remains undefined because of insufficient targeted clinical data. This study aimed to compare the short-term outcomes of D3 versus non-D3 LND in Stage II–III CRC in oldest-old patients. Methods This retrospective cohort study utilized data from the Setouchi Colorectal Neoplasm Registration database, including 282 oldest-old patients with CRC treated between 2011 and 2022. Patients were stratified into D3 and non-D3 LND groups, with inverse-probability-weighted regression adjustment implemented to address potential confounding factors. Postoperative complications and hospital stays were analyzed using regression models and descriptive statistics. Results D3 LND resulted in significantly higher lymph node harvests in both Stage II and Stage III patients (p < 0.01). There were no significant differences in overall or major postoperative complications between D3 and non-D3 groups. Hospital stays were comparable for Stage II patients but shorter for Stage III patients in the D3 group (p < 0.01). Complication rates ranged from 28% to 47.7%, with surgical site infections and pneumonia being the most common. Conclusions D3 LND can be safely performed in oldest-old patients with CRC without increasing postoperative complications or extending hospital stays. These findings support the feasibility of extensive LND in this age gr 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 A Case of Psoas Abscess Diagnosed With Oral Bacteria as the Causative Pathogen e97584 EN Koki Umemori Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine Kyoichi Obata Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine Mayumi Yao Dentistry and Dental Surgery, Tsuyama Central Hospital Koji Fujita General Internal Medicine and Infectious Diseases, Tsuyama Central Hospital Soichiro Ibaragi Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine We report a rare case of a psoas abscess in an 87-year-old woman, in which oral commensal bacteria may have disseminated hematogenously from a chronic oral infection site and served as the causative pathogens. The patient presented with persistent left buttock pain, fever, and swelling, and imaging revealed a fracture of the left iliac bone with an associated psoas abscess. Bacterial cultures identified Streptococcus oralis and Pseudomonas aeruginosa. Her symptoms improved following antibiotic therapy and CT-guided drainage. Although the presence of P. aeruginosa in the oral cavity is generally considered transient, it has been isolated from the oral cavities of elderly and immunocompromised individuals. In the absence of lacerations or other direct portals of entry, and considering the identification of both pathogens, the oral cavity was regarded as the most likely source of infection. This case highlights the importance of correlating culture results with the most probable source of infection to improve the prognosis of systemic infections. No potential conflict of interest relevant to this article was reported.

Japanese Society for Horticultural Science Acta Medica Okayama 2189-0102 94 4 2025 Effects of Intermittent Low-temperature Storage Duration and Cycle on the Bolting and Flowering of Delphinium elatum in Summer 522 529 EN Mika Kawai Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Miwa Fukuyasu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiyuki Tanaka Graduate School of Agriculture, Kyoto University Yoshikuni Kitamura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ken-ichiro Yasuba Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuichi Yoshida Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tanjuro Goto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Early-bolting in summer is a major problem when growing delphinium seedlings in summer to produce cut flowers that will be shipped in autumn and winter. In this study, an intermittent low-temperature storage (ILTS) treatment that induces flower bud differentiation in strawberry and prevents rosette formation in Eustoma significantly increased the Delphinium elatum cut flower length. Moreover, ILTS was as effective as growing seedlings under cool conditions at preventing early-bolting. We analyzed the effects of six ILTS treatments that differed regarding the treatment temperature (5 and 10°C) and treatment cycle (3 days/3 days, 6 days/6 days, and 12 days/12 days; ambient conditions/cool and dark). Cut flowers were significantly longer with the 6 days/6 days treatment at 10°C than for the control treatment. Furthermore, repeating the ILTS treatment cycle (6 days ambient conditions/6 days at 10°C) a total of four times produced high-quality cut flowers regardless of the cultivar. Therefore, this ILTS treatment may be ideal for preventing early-bolting in D. elatum. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1664-462X 16 2025 Structural analysis of PSI-ACPI and PSII-ACPII supercomplexes from a cryptophyte alga Rhodomonas sp. NIES-2332 1716939 EN Wenyue Zhang Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nozomi Yonehara Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mizuki Ishii Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haowei Jiang Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Romain La Rocca Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Pi-Cheng Tsai Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hongjie Li Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Koji Kato Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Fusamichi Akita Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Jian-Ren Shen Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Light energy is converted to chemical energy by two photosystems (PSI and PSII) in complex with their light-harvesting complex proteins (LHCI and LHCII) in photosynthesis. Rhodomonas is a member of cryptophyte alga whose LHCs contain unique chlorophyll a/c proteins (ACPs) and phycobiliproteins. We purified PSI-ACPI and PSII-ACPII supercomplexes from a cryptophyte Rhodomonas sp. NIES-2332 and analyzed their structures at high resolutions of 2.08 Å and 2.17 Å, respectively, using cryo-electron microscopy. These structures are largely similar to those reported previously from two other species of cryptophytes, but exhibited some differences in both the pigment locations and subunit structures. A part of the antenna subunits of both photosystems is shifted compared with the previously reported structures from other species of cryptophytes, suggesting some differences in the energy transfer rates from the antenna to the PSI and PSII cores. Newly identified lipids are found to occupy the interfaces between the antennae and cores, which may be important for assembly and stabilization of the supercomplexes. Water molecules surrounding three iron-sulfur clusters of the PSI core are found in our high-resolution structure, some of which are conserved from cyanobacteria to higher plants but some are different. In addition, our structure of PSII-ACPII lacks the subunits of oxygen-evolving complex as well as the Mn4CaO5 cluster, suggesting that the cells are in the S-growth phase, yet the PSI-ACPI structure showed the binding of PsaQ, suggesting that it is in an L-phase. These results suggest that the S-phase and L-phase can co-exist in the cryptophytic cells. The high-resolution structures of both PSI-ACPIs and PSII-ACPIIs solved in this study provide a more solid structural basis for elucidating the energy transfer and quenching mechanisms in this group of the organisms. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1757-2215 19 1 2025 Pan-cancer profiling links C1orf50 to DNA repair and immune modulation in ovarian cancer 13 EN Anna Rogachevskaya Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School Yusuke Otani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Akira Ohtsu Harvard Medical School Vanessa D. Chin UMass Chan Medical School, UMass Memorial Medical Center Tirso Peña Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School Seiji Arai Department of Urology, Gunma University Graduate School of Medicine Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Atsushi Fujimura Department of Molecular Physiology, Faculty of Medicine, Graduate School of Medicine, Kagawa University Atsushi Tanaka Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School Background C1orf50 encodes a small, evolutionarily conserved protein, the function of which remains unclear. Its significance across various human cancers, particularly its specific role in ovarian cancer within an immunogenomic context, is not yet fully understood. Utilizing The Cancer Genome Atlas and single-cell RNA sequencing (scRNA-seq) public datasets, we conducted a comprehensive profiling of C1orf50 across multiple cancer types, with a particular focus on ovarian cancer, to investigate its associations with copy-number status, genomic instability, tumor programs, and the immune microenvironment. Results Across cancer types, copy-number gain or amplification of C1orf50 was most frequent in ovarian cancer and closely tracked with higher messenger RNA levels. Higher C1orf50 expression was associated with a greater tumor mutational burden and homologous recombination deficiency, as indicated by gene-set patterns that suggested heightened cell-cycle and cellular stress responses accompanied by reduced oxidative phosphorylation, enrichment of regulatory T cells, and depletion of resting memory CD4 T cells. In ovarian cancer, focal events at chromosome 1p34.2 were accompanied by stepwise increases in C1orf50 expression by clinical stage and were linked to higher tumor mutational burden, homologous recombination deficiency, and greater loss of heterozygosity, together with more frequent gene alterations in BRCA1 or BRCA2. Immune composition clustered into profiles consistent with an immunosuppressive context in tumors with higher C1orf50 expression. The scRNA-seq data further revealed that cancer cells enhanced immune-suppressive interactions with various immune cell populations and diminished antigen-presentation signals. Analyses of genomic instability in ovarian cancer suggested mutational processes compatible with base-substitution patterns associated with cytidine deaminase activity and with insertion-deletion patterns characteristic of homologous recombination failure, while transcript-level patterns pointed to a broad downshift of canonical DNA repair activity with apparent compensatory adjustments in related pathways rather than a uniform change in any single pathway. Conclusions The overexpression of C1orf50 characterizes an aggressive immunogenomic phenotype in ovarian cancer, distinguished by genomic instability, impaired DNA repair mechanisms, and extensive immunosuppression. These findings indicate that C1orf50 warrants consideration as a potential biomarker and a prospective target for therapeutic investigation. Furthermore, they advocate for the progression to prospective validation and functional studies to ascertain its clinical significance. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1546-0096 24 1 2026 TeMPRA: advancing continuing professional development in pediatric rheumatology in Japan EN Hiroyuki Wakiguchi Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine Kunio Hashimoto Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences Masato Yashiro Department of Pediatrics, Okayama University Hospital Kenichi Nishimura Department of Pediatrics, Yokohama City University Graduate School of Medicine Takasuke Ebato Department of Pediatrics, Kitasato University Keiji Akamine Department of Nephrology and Rheumatology, Tokyo Metropolitan Children’s Medical Center Yoji Uejima Division of Infectious Diseases and Immunology, Saitama Children’s Medical Center Tomomi Sato Clinical Education Center for Physicians, Shiga University of Medical Science Yuichi Yamasaki Department of Pediatrics, Kagoshima University Hospital Junko Yasumura Department of Pediatrics, Hiroshima Prefectural Hospital Organization Futabanosato Prefectural Hospital Fumiko Okazaki Department of Pediatrics, Yamaguchi University Graduate School of Medicine Toshitaka Kizawa Department of Pediatrics, Japan Community Health Care Organization Sapporo Hokushin Hospital Ryuhei Yasuoka Department of Pediatrics, Hamamatsu University School of Medicine Tomoaki Ishikawa Department of Pediatrics, Nara Medical University Takeshi Yamamoto Department of Pediatrics, Chiba University Graduate School of Medicine Yuji Fujita Department of Pediatrics, Dokkyo Medical University Naohiro Itoh Department of Pediatrics, Faculty of Medical Sciences, University of Fukui Asami Takasaki Department of Pediatrics, School of Medicine, University of Toyama Nodoka Sakurai Department of Pediatrics, NTT East Medical Center Sapporo Kazuo Suzuki Suzuki Kids Clinic Tasuku Tamai Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine Naoki Hirano Department of Public Health and Epidemiology, Faculty of Medicine, Oita University Nami Okamoto Department of Pediatrics, Osaka Rosai Hospital, Japan Organization of Occupational Health and Safety Masaki Shimizu Department of Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo Background In the context of the global shortage of pediatric rheumatologists, mid-career specialists who can play key roles in regional education, research, and clinical practice have become increasingly important. In Japan, the Team of Mid-career Pediatric Rheumatologists Alliance (TeMPRA) was founded in 2014 to support continuing professional development (CPD) and foster collaboration among mid-career pediatric rheumatologists. The aim of this study was to characterize the current status and future perspectives of the TeMPRA members. Methods In 2024, a cross-sectional, web-based survey was conducted among all 37 active members of the TeMPRA across Japan. Data were collected on career trajectories, educational roles, research activities, clinical practices, and international engagement. Categorical variables were compared using appropriate statistical tests, with a significance level of 0.05. Results Responses were obtained from 35 members (response rate: 95%). Most respondents (71%) were affiliated with university hospitals, and 60% had > 10 years of experience in pediatric rheumatology. Compared with those working in community hospitals, respondents affiliated with university hospitals were significantly more likely to be involved in research activities (50% vs. 0%, P = 0.0261) and global professional contributions (88% vs. 0%, P < 0.0001). Overall, 54% of respondents were engaged in teaching students or early-career pediatric rheumatologists, while 43% were involved in clinical or basic research, most commonly focusing on juvenile idiopathic arthritis and systemic lupus erythematosus. Collectively, respondents were responsible for the care of 1,677 children with pediatric rheumatic diseases. While all respondents reported willingness to contribute to pediatric rheumatology at the regional level, 94% and 71% reported willingness to contribute at the national and global levels, respectively. Conclusions This nationwide survey highlights the substantial educational roles, research activities, and clinical practices of mid-career pediatric rheumatologists in Japan and suggests that the TeMPRA framework can serve as a valuable model for supporting CPD and workforce sustainability. Similar alliance-based approaches may be applicable in other countries facing comparable challenges in pediatric rheumatology. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 2589-0042 28 9 2025 Extensive urine production in euryhaline red stingray for adaptation to hypoosmotic environments 113274 EN Naotaka Aburatani Atmosphere and Ocean Research Institute, The University of Tokyo Wataru Takagi Atmosphere and Ocean Research Institute, The University of Tokyo Marty Kwok-Shing Wong Atmosphere and Ocean Research Institute, The University of Tokyo Nobuhiro Ogawa Atmosphere and Ocean Research Institute, The University of Tokyo Shigehiro Kuraku Department of Genomics and Evolutionary Biology, National Institute of Genetics Mana Sato Department of Genomics and Evolutionary Biology, National Institute of Genetics Kazuhiro Saito Ushimado Marine Institute, Faculty of Science, Okayama University Waichiro Godo Ushimado Marine Institute, Faculty of Science, Okayama University Tatsuya Sakamoto Ushimado Marine Institute, Faculty of Science, Okayama University Susumu Hyodo Atmosphere and Ocean Research Institute, The University of Tokyo Maintaining water balance is a prerequisite for all organisms. Euryhaline elasmobranchs face the severest water-influx potential in fresh water (FW), as they retain high concentrations of urea even in hypotonic environments. To elucidate how they overcome this osmotic challenge, we assessed urine output in conscious euryhaline red stingrays (Hemitrygon akajei). Following acclimation to 5% diluted seawater, the stingrays increased urinary output by 87-fold—the greatest change observed in vertebrates—partly due to 6.8-fold increase in glomerular filtration rate (GFR). In the nephron, expressions of Aquaporin-1 (Aqp1), Aqp3, and Aqp15 were strongly downregulated in FW, indicating that tubular diuresis bridges the gap between GFR and final urine volume. Meanwhile, FW-acclimation upregulated Aqp1 and Aqp4 in the distinct bundle structure, which promotes urea reabsorption. Euryhaline elasmobranchs resolve the huge osmotic challenge of FW by excreting massive amounts of water and retaining osmolytes including urea through coordinated regulation of GFR and Aqp expressions. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2352-5789 59 2025 Evaluation of platinum-free interval and chemotherapeutic effect of subsequent platinum-containing chemotherapy in patients with recurrent ovarian cancer initially treated with bevacizumab: SGSG018/Intergroup study 101740 EN Tamaki Tanaka Department of Perinatology and Gynecology, Kagawa University Graduate School of Medicine Kazuhiro Takehara Department of Gynecologic Oncology, NHO Shikoku Cancer Center Tomoka Usami Department of Obstetrics and Gynecology, Ehime University Graduate School of Medicine Masako Ishikawa Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine Eiji Kondo Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine Masahiro Kagabu Department of Obstetrics and Gynecology, Iwate Medical University Kei Hirabayashi Department of Obstetrics and Gynecology, JCHO Tokuyama Central Hospital Noriomi Matsumura Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine Shinya Sato Department of Obstetrics and Gynecology, Faculty of Medicine Tottori University Masato Nishimura Department of Obstetrics and Gynecology, Tokushima Prefectural Central Hospital Atsushi Arakawa Department of Obstetrics and Gynecology, Nagoya City University West Medical Center Keiichiro Nakamura Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Konno Department of Obstetrics and Gynecology, Hokkaido University Hospital Satoe Fujiwara Department of Obstetrics and Gynecology, Osaka Medical and Pharmaceutical University Kotaro Sueoka Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine Hiroko Nakamura Department of Obstetrics and Gynecology, NHO Kure Medical Center and Chugoku Cancer Center Iemasa Koh Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Hiroshima University Kimihiko Ito Department of Obstetrics and Gynecology, Kansai Rosai Hospital Atsushi Hongo Department of Obstetrics and Gynecology, Kansai Rosai Hospital Objective: The effect of bevacizumab on platinum sensitivity in recurrent ovarian cancer remains poorly understood. This study examined the association between platinum-free interval (PFI) and sensitivity to subsequent platinum-containing chemotherapy in patients with first relapsed ovarian cancer after bevacizumab chemotherapy. Methods: We retrospectively analyzed patients who received platinum-based chemotherapy for platinum-sensitive recurrence between November 2013, and December 2019, and who were initially treated by platinum-based chemotherapy with concurrent and maintenance bevacizumab. The primary endpoint was response rate to subsequent chemotherapy after various periods of PFI. The relevance between response rate and PFI was assessed for each PFI of 6–12, 12–24 and ≧24 months using Cochran-Armitage test. The secondary endpoint was progression-free survival (PFS) defined as time from chemotherapy for first recurrence to subsequent progression and response rate to subsequent chemotherapy for each treatment-free interval since last administration of bevacizumab (Bev-TFI). Results: A total of 77 patients were eligible. The median PFI until first recurrence was 12 months (range: 6–43). The response rates of subsequent chemotherapy for patients with PFI of 6–12, ≥12-24, and 24 months were 42 %, 65 %, and 80 %, showing a linear trend (p < 0.05). Median PFS among the three groups was 8 (95 %CI: 6.7–9.2), 11 (95 %CI: 8.4–13.5) and 13 months (95 % CI: 5.4–20.5) (p = 0.107, log-rank test), respectively. By contrast, no linear trend was observed between Bev-TFI and response rate (p = 0.225) Conclusion: In patients with first relapse of primary ovarian cancer and bevacizumab beyond progression, the prolonged PFS effect of bevacizumab does not seem to affect sensitivity to subsequent platinum-based chemotherapy. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1068-9265 32 12 2025 Mesenteric Route Superior Mesenteric Artery First Approach in Robot-Assisted Pancreatoduodenectomy 8903 8905 EN Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atene Ito Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takeyoshi Nishiyama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tsubasa Yanagihara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background. The superior mesenteric artery (SMA) approach is crucial for the successful implementation of robot-assisted pancreatoduodenectomy (RPD). Herein, we present a novel technique, the mesenteric route SMA-first approach, for RPD. Patients and Methods. A 20-year-old woman with a 50 mm intraductal papillary mucinous neoplasm underwent RPD. As the tumor was large and located close to the mesenteric vessels, we developed the mesenteric route SMA-first approach. Results. Following the mesenteric Kocher maneuver, the mesenteric route SMA-first approach was applied. With appropriate retraction of the pancreatic head, dissection around the mesenteric vessels was performed and their branches were divided. The uncinate process dissection (PL, ph II) was performed via the mesenteric route. This approach facilitated dorsal dissection, particularly around the large tumor. After dissection of the hepatoduodenal ligament, the remaining pancreatic nerve plexus (PL ph I) was dissected. Finally, the pancreas was divided on the superior mesenteric vein, and the specimen was resected. Operative time was 390 min with minimal blood loss. Conclusions. The mesenteric route SMA-first approach enables uncinate process dissection via the mesenteric route. This technique may be a safe and feasible option for selected patients, such as nonobese individuals with a large pancreatic head tumor near major vessels. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 2210-2612 133 2025 Robotic pancreatoduodenectomy for a giant duodenal leiomyoma: A case report and literature review 111546 EN Susumu Doita Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Motohiko Yamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Introduction: Duodenal leiomyomas are rare mesenchymal tumors. To date, several studies have reported on the safety and feasibility of surgical intervention for duodenal leiomyomas. However, minimally invasive surgery has rarely been performed in cases with duodenal leiomyomas. Herein, we present a case of a giant duodenal leiomyoma successfully treated with robotic pancreatoduodenectomy (RPD). Presentation of case: A 74-year-old man was referred to our hospital with a 6.5 cm duodenal tumor accompanied by gastrointestinal bleeding. The tumor was located in the second portion of the duodenum. Considering the tumor size and location, RPD was performed. Using the mesenteric Kocker maneuver, the posterior side of the duodenum was safely dissected, and the tumor was resected. The operative time was 373 min, with an estimated blood loss of 10 mL. The patient was followed up for 7 months with no recurrence. Discussion: To the best of our knowledge, this is the first to highlight the clinicopathological findings of a patient with duodenal leiomyoma undergoing RPD. To date, there have been 19 cases, including our case, reporting surgically treated duodenal leiomyoma. Treatment strategies should be decided depending on tumor characteristics, including the size, location, and histology of the tumor. Conclusion: We present a rare case of a giant duodenal leiomyoma that was successfully treated with RPD. Minimally invasive surgery can be safe and an alternative for the treatment of large duodenal tumors. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1435-2451 410 1 2025 Robotic distal pancreatectomy using two-surgeon technique (TAKUMI-4): a technical note and initial outcomes 171 EN Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Purpose With the increasing use of minimally invasive distal pancreatectomy, the use of robotic distal pancreatectomy (RDP) is also increasing worldwide. Standardized surgical protocols are essential for safe implementation of RDP. In this study, we present our surgical protocol and initial outcomes of RDP using “two-surgeon technique”. Methods Our standard RDP protocol included a two-surgeon technique for cooperation, rationality, and education. Short-term outcomes of RDP were also investigated. This retrospective study included 77 consecutive patients who underwent RDP at our institution between April 2021 and January 2025. Results The median operative time, estimated blood loss, and postoperative hospital stay were 214 min (interquartile range [IQR], 176–253), 10 mL (IQR, 0–50), and 9 days (IQR, 8–10), respectively. A textbook outcome was achieved in 84.4% of patients. Moreover, superior outcomes of RDP (n = 77) compared with those of laparoscopic distal pancreatectomy (n = 62) were confirmed in this study. Conclusion Using the two-surgeon technique, we successfully standardized and introduced the RDP program. The two-surgeon technique can contribute to the safe introduction of RDP and expansion of the program. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0930-2794 39 5 2025 Impact of visceral fat area on surgical difficulty during robotic distal pancreatectomy (TAKUMI-2) 3137 3145 EN Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Motohiko Yamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takeyoshi Nishiyama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Noriyuki Kanehira Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: Difficulty scoring systems (DSS) have been developed to quantify the surgical complexity of laparoscopic distal pancreatectomy (LDP). However, few studies have validated these systems in the context of robotic distal pancreatectomy (RDP). Moreover, the impact of body composition on RDP outcomes remains unexplored. This study aimed to investigate the risk factors of surgical difficulty in RDP, including body composition. Methods: This retrospective study included 72 consecutive patients who underwent RDP at our institution between April 2021 and October 2024. Using a modified DSS for LDP, patients were divided into three difficulty index groups. The association between the difficulty index and outcomes was investigated. Multivariate analyses were performed to identify risk factors associated with surgical difficulty (prolonged operative time) in RDP. Results: Patients were classified into three difficulty index groups: low (n = 28), intermediate (n = 25), and high (n = 19). Operative time was significantly associated with the surgical index (P = 0.01). Moreover, visceral fat area (VFA) was significantly correlated with operative time (r2 = 0.10, P = 0.008). The multivariate analyses found that VFA (≥ 100 cm2) (odds ratio [OR] 5.03, 95% confidence interval [CI] 1.32–22.4, P = 0.02), malignancy (OR 4.92, 95% CI 1.50–18.9, P = 0.01), and pancreatic resection on the portal vein (OR 4.14, 95% CI 1.24–15.9, P = 0.02) were significant risk factors associated with surgical difficulty. Conclusion: VFA could be a novel and useful factor for assessing the surgical difficulty associated with RDP. No potential conflict of interest relevant to this article was reported.

Japan Medical Association Acta Medica Okayama 2433-3298 8 2 2025 A Case of Hepatocellular Carcinoma Associated with Hepatic Sarcoidosis 606 608 EN Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Kariyama Department of Gastroenterology, Okayama City Hospital Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1758-5902 18 1 2025 Metachronous Pancreatic Metastasis of Myxoid Liposarcoma Successfully Treated With Robotic Spleen‐Preserving Distal Pancreatectomy With Splenic Vessels Resections: A Case Report e70069 EN Yumi Sota Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Motohiko Yamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takeyoshi Nishiyama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Noriyuki Kanehira Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akari Masunaga Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Pancreatic metastasis of myxoid liposarcoma (MLS) after primary resection is extremely rare. Herein, we present a case of metachronous pancreatic metastasis of MLS that was successfully treated with robotic spleen-preserving distal pancreatectomy (SPDP) using the Warshaw technique. A 60-year-old woman underwent radical resection of a 25-cm MLS in the right thigh after receiving neoadjuvant radiotherapy. The patient developed a 6-cm solitary pancreatic metastasis of the MLS 2 years later. Because no other distant metastases were detected, robotic SPDP (Warshaw technique) was performed. The operative time was 140 min with minimal blood loss. Follow-up at 3 months showed no recurrence. To our knowledge, this is the first report of a case of metachronous pancreatic metastasis of MLS successfully treated with robotic SPDP. Curative resection using minimally invasive surgery should be performed for solitary pancreatic metastases from MLS. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2589-5370 80 2025 Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone combined with high-dose methotrexate plus intrathecal chemotherapy for newly diagnosed intravascular large B-cell lymphoma (PRIMEUR-IVL): long-term results of a multicentre, single-arm, phase 2 trial 103078 EN Kazuyuki Shimada Department of Hematology and Oncology, Nagoya University Graduate School of Medicine Motoko Yamaguchi Department of Hematological Malignancies, Mie University Graduate School of Medicine Yachiyo Kuwatsuka Department of Advanced Medicine, Nagoya University Hospital Kosei Matsue Division of Hematology/Oncology, Internal Medicine, Kameda Medical Center Keijiro Sato Department of Hematology, Nagano Red Cross Hospital Shigeru Kusumoto Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences Hirokazu Nagai Department of Hematology, National Hospital Organization Nagoya Medical Center Jun Takizawa Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine Noriko Fukuhara Department of Hematology and Rheumatology, Tohoku University Hospital Koji Nagafuji Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine Kana Miyazaki Department of Hematology and Oncology, Mie University Graduate School of Medicine Eiichi Ohtsuka Department of Hematology, Oita Prefectural Hospital Akinao Okamoto Department of Hematology, Fujita Health University School of Medicine Yasumasa Sugita Department of Hematology, Oami Municipal Hospital Toshiki Uchida Department of Hematology and Oncology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital Satoshi Kayukawa Department of Clinical Oncology, Nagoya Memorial Hospital Atsushi Wake Department of Hematology, Toranomon Hospital Kajigaya Daisuke Ennishi Department of Hematology and Oncology, Okayama University Hospital Yukio Kondo Department of Internal Medicine, Toyama Prefectural Central Hospital Akiko Meguro Division of Hematology, Tochigi Cancer Center Yoshihiro Kin Department of Hematology, Daini Osaka Police Hospital Yosuke Minami Department of Hematology, National Cancer Center Hospital East Daigo Hashimoto Department of Hematology, Hokkaido University Faculty of Medicine, Graduate School of Medicine Takahiro Nishiyama Division of Hematology, Ichinomiya Municipal Hospital Satoko Shimada Department of Pathology and Clinical Laboratories, Nagoya University Hospital Yasufumi Masaki Department of Hematology and Immunology, Kanazawa Medical University Masataka Okamoto Department of Hematology, Fujita Health University School of Medicine Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation Hitoshi Kiyoi Department of Hematology and Oncology, Nagoya University Graduate School of Medicine Ritsuro Suzuki Department of HSCT Data Management and Biostatistics, Nagoya University School of Medicine Shigeo Nakamura Department of Pathology and Clinical Laboratories, Nagoya University Hospital Tomohiro Kinoshita Department of Hematology and Cell Therapy, Aichi Cancer Center Background Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma for which prognosis is typically poor without a timely diagnosis. To explore the safety and efficacy of standard chemotherapy combined with central nervous system (CNS)-directed therapy, we conducted a multicentre, single-arm, phase 2 trial in untreated IVLBCL patients without CNS involvement at diagnosis (PRIMEUR-IVL). In the primary analysis, the PRIMEUR-IVL study demonstrated 2-year progression-free survival (PFS) of 76% and 2-year overall survival (OS) of 92% with a low incidence (3%) of secondary CNS involvement (sCNSi). Methods We present a prespecified final analysis of the PRIMEUR-IVL study including 5-year PFS, OS and cumulative incidence of sCNSi. Participants were enrolled between June 2011 and July 2016, and the data cutoff date for the final analysis was 16 November 2021. The trial was registered in the UMIN Clinical Trial Registry (UMIN000005707) and the Japan Registry of Clinical Trials (jRCTs041180165). Findings With a median follow-up of 7.1 years (interquartile range 5.6–8.7), 5-year PFS in all 37 eligible patients was 68% (95% confidence interval [CI] 50%–80%) and OS was 78% (95% CI 61%–89%). No additional sCNSi was observed after the primary analysis. Severe adverse events after the primary analysis were grade 4 neutropenia (n = 1) and grade 4 myelodysplastic syndrome that did not require specific treatment (n = 1). Eight deaths occurred during the observation period after enrolment, due to primary disease (n = 6), sepsis (n = 1) and unknown sudden death (n = 1). Interpretation Long-term follow-up data demonstrated durable response for PFS and OS, and low cumulative incidence of sCNSi, indicating the efficacy of standard chemotherapy combined with CNS-directed therapy for untreated IVLBCL patients. Funding This study received financial support from the Japan Agency for Medical Research and Development, Center for Supporting Hematology-Oncology Studies, and National Cancer Center. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 30 7 2025 How to report and discuss subgroup analyses in clinical practice guidelines? Evaluation procedure of the clinical and statistical relevancy 1259 1267 EN Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Satoru Miura Department of Internal Medicine, Niigata Cancer Center Hospital Yuko Oya Department of Respiratory Medicine and Allergy, Fujita Health University Tomohiro Sakamoto Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Tottori University Kentaro Tanaka Graduate School of Medical Sciences, Research Institute for Diseases of the Chest, Kyushu University Shunsuke Teraoka Internal Medicine III, Wakayama Medical University Masahiro Morise Department of Respiratory Medicine, Nagoya University Graduate School of Medicine Satoshi Morita Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University The results of subgroup analyses of clinical trials are important reference information when considering the generalizability of a study treatment, i.e., providing the best treatment for each individual patient. The results of subgroup analyses are often presented in publications, etc. as forest plots focusing on patient backgrounds. However, it is important to fully understand and grasp some of the issues involved in subgroup analyses and to interpret the results carefully to apply them in clinical practice. Although the literature includes some reports on how subgroup analyses should be evaluated and handled for the purpose of establishing medical practice guidelines, most of the papers have mainly evaluated the reliability of subgroup analyses from a statistical perspective; few of them have incorporated clinical importance in their evaluations. Therefore, in December 2019, we established a Subgroup Analysis Review Committee consisting of oncologists specializing in lung cancer treatment and statistical experts among the members of the Guidelines Review Committee of the Japanese Lung Cancer Association, with the aim of appropriately reflecting subgroup analysis in Japanese lung cancer practice guidelines. We developed a new evaluation strategy to incorporate clinical aspects as well as reliability assessment. Specifically, on the basis of a clinical and statistical review of the problems with subgroup analyses presented as clinical trial results, we developed criteria and procedures to ensure consistency and fairness in the citation of clinical guidelines. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 6 2025 Retreatment With EGFR-Tyrosine Kinase Inhibitor After Disease Progression Following Gefitinib Induction and Chemoradiotherapy in EGFR-Mutant Stage III Non-small Lung Cancer: An Efficacy and Safety Analysis of the LOGIK0902/OLCSG0905 Study e86575 EN Sho Saeki Department of Respiratory Medicine, Kumamoto University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Shinya Sakata Department of Respiratory Medicine, Kumamoto University Hospital Naohiro Oda Department of Respiratory Medicine, Okayama University Hospital Koji Inoue Department of Respiratory Medicine, Kitakyushu Municipal Medical Center Tomoki Tamura Department of Respiratory Medicine, Okayama University Hospital Ryo Toyozawa Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center Daijiro Harada Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center Kentaro Tanaka Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University Koji Inoue Department of Respiratory Medicine, Ehime Prefectural Central Hospital Yoshiyuki Shioyama Radiation Oncology, Ion Beam Therapy Center, SAGA HIMAT Foundation Kenichi Gemba Department of Respiratory Medicine, Chugoku Central Hospital Tomonari Sasaki Department of Radiation Oncology, Iizuka Hospital Akihiro Bessho Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Junji Kishimoto Center for Clinical and Translational Research, Kyushu University Hospital Kuniaki Katsui Department of Radiology, Division of Radiation Oncology, Kawasaki Medical School Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Kenji Sugio Thoracic and Breast Surgery, Oita University Background and objective: We had previously conducted a phase II study (LOGIK0902/OLCSG0905 study) involving the eight-week administration of gefitinib, followed by cisplatin-based chemoradiotherapy, to treat locally advanced, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC). Despite favorable overall survival outcomes, more than half of the patients relapsed after the protocol therapy, highlighting the need to clarify the clinical significance of retreatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated the efficacy and safety of EGFR-TKI retreatment after disease progression. Materials and methods: We included 14 patients who relapsed after the protocol treatment and received any type of EGFR-TKI as post-progression treatment in this sub-analysis. We evaluated the efficacy and safety of retreatment with EGFR-TKI in these patients. Results: Among the 14 patients, 11 (78.6%) responded to the induction of gefitinib in the treatment protocol. After relapse, 9/14 patients (64.3%) received gefitinib, 3/14 (21.4%) received afatinib, and 2/14 (14.3%) received erlotinib monotherapy, respectively. The median duration of post-progression EGFR-TKI treatment was 17.9 (0.7-45.5) months. The overall response rate (ORR) and disease control rate were 64.3% [9/14 patients; 95% confidence interval (CI): 35.1%-87.2%] and 85.7% (12/14 patients; 95% CI: 57.2%-98.2%), respectively. The median progression-free survival (PFS) and median survival durations after the initiation of EGFR-TKI retreatment were 11.8 months (95% CI: 5.7-20.7 months) and 47.4 months (95% CI: 31.8 months to not estimable), respectively. Adverse events were comparable to those previously reported. Conclusions: Patients with disease progression after protocol therapy demonstrated sensitivity to retreatment with an EGFR-TKI, with acceptable safety. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 64 14 2025 Myeloid Sarcoma in the Small Intestine 2155 2159 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohiro Kamio Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shoichiro Hirata Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Katsunori Matsueda Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daisuke Kametaka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Myeloid sarcoma is a rare extramedullary tumor of immature myeloid cells that is often associated with acute myeloid leukemia (AML). We herein report an 81-year-old man who presented with intestinal obstruction due to myeloid sarcoma of the small intestine. Diagnostic challenges were overcome using double-balloon enteroscopy and a biopsy, which confirmed the diagnosis of myeloid sarcoma. The patient subsequently developed AML but responded well to chemotherapy. This case underscores the importance of considering myeloid sarcoma in the differential diagnosis of small-bowel tumors. Highlighting the significance of a histological analysis, even in patients presenting with small bowel obstruction, the early diagnosis and treatment are crucial for improving outcomes, particularly in patients without a history of hematologic malignancies. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 5 2025 Pseudoachalasia Due to Malignant Pleural Mesothelioma Involving the Esophagus e84161 EN Manami Honda 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 Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences We report a rare case of pseudoachalasia secondary to malignant pleural mesothelioma involving the esophagus. A 66-year-old man presented with progressive dysphagia, weight loss, and postprandial hiccups. Endoscopic examination showed esophageal dilation with luminal narrowing at the esophagogastric junction, but no mucosal abnormalities. Computed tomography revealed an irregular-shaped mass extending from the peri-esophagogastric junction to the retroperitoneum, accompanied by pleural effusion, right-sided hydronephrosis, and multiple hepatic lesions. Endoscopic ultrasound-guided fine-needle aspiration from the mass lesion through the esophageal lumen revealed epithelioid malignant mesothelioma. This case highlights the importance of considering malignant mesothelioma in the differential diagnosis of pseudoachalasia, particularly when imaging reveals extrinsic esophageal compression without mucosal lesions. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 4 2025 Gastrointestinal Stromal Tumors in the Stomach With Tumor Growth and Hemorrhage During Conservative Management: A Report of Two Cases e82046 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Gastroenterological Surgery, 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 Gastrointestinal stromal tumors (GISTs) are often detected incidentally during esophagogastroduodenoscopy. Although surgical resection is the standard treatment for GISTs, patients with significant comorbidities may not be eligible for surgery and are managed conservatively. Herein, we report two cases of gastric GISTs that were initially observed during the management of other comorbidities but subsequently became enlarged, resulting in gastrointestinal bleeding. These cases highlight the potential risks of tumor progression and bleeding in patients undergoing conservative management. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1865-7257 18 2 2025 Microsatellite-high intrahepatic cholangiocarcinoma with favorable treatment outcome using pembrolizumab 363 368 EN Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Hospital Kosaku Morimoto Department of Gastroenterology and Hepatology, Okayama University Hospital Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Hiroyuki Terasawa Department of Gastroenterology and Hepatology, Okayama University Hospital Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Takehiro Tanaka Department of Pathology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Intrahepatic cholangiocarcinoma has a poor prognosis. In unresectable cases, the survival period is short despite combination therapy with cytotoxic anticancer agents and immune checkpoint inhibitors. The usefulness of immune checkpoint inhibitors against malignant tumors with microsatellite instability-high (MSI-H) mutations was shown in the KEYNOTE158 study; however, data for intrahepatic cholangiocarcinoma are insufficient. In the present case, a 65-year-old man with intrahepatic cholangiocarcinoma and lymph node metastasis could not be treated with a combination of gemcitabine, CDDP, and S-1. A comprehensive cancer genomic profiling (CGP) test showed MLH1 pathogenic mutation and MSI-H. When pembrolizumab was administered, the tumor shrinkage effect was rapidly observed, which was sustained even after 30 months. No pathogenic mutations were observed in the germline test, and MSI-high was considered to be due to the MLH1 pathogenic mutation occurring sporadically in somatic cells. MSI-H intrahepatic cholangiocarcinoma is extremely rare. However, because pembrolizumab is expected to be effective, CGP testing should be actively performed. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 2 2025 Gastric Metastasis of Renal Cell Carcinoma Initially Diagnosed by Esophagogastroduodenoscopy e79651 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohiro Kamio Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shoichiro Hirata Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Here, we report a rare case of renal cell carcinoma (RCC) initially detected as a gastric metastasis. A 58-year-old man with epigastric discomfort underwent esophagogastroduodenoscopy, which revealed a reddish semi-pedunculated lesion with a whitish coating. Biopsy and imaging confirmed clear cell RCC metastasis. Contrast-enhanced computed tomography (CT) revealed a primary renal tumor with pancreatic and lymph node metastases. Despite chemotherapy treatment, the patient died after 10 months. Gastric metastases from RCC, although rare, should be considered in highly vascular gastric lesions with white coatings. Clinicians must be vigilant for metastatic diseases with atypical gastric findings. No potential conflict of interest relevant to this article was reported.

IOP Publishing Acta Medica Okayama 1742-6588 3027 1 2025 LES analysis to investigate a random-phase forcing scheme for steadying anisotropic turbulence fields 012009 EN Koki Minami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroki Suzuki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Toshinori Kouchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kento Tanaka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The aim of this study is to investigate the effect of phase randomization on forcing mechanisms that stabilize localized turbulence. A trigonometric forcing based on vector potential is combined with uniform random numbers to create a spatially homogeneous forcing field. The analysis is performed using large-eddy simulation (LES) with the Smagorinsky model as the subgrid scale model. The results demonstrate that steady flows are generated regardless of the presence of phase randomization, successfully forming isotropic turbulence. In contrast, for anisotropic turbulent fields, the addition of phase randomization reduces the degree of anisotropy, indicating a smoothing effect on the anisotropy of the flow. No potential conflict of interest relevant to this article was reported.

IOP Publishing Acta Medica Okayama 1742-6588 3027 1 2025 Fundamental examination of coherent structure model prediction using vortex cores in a two-dimensional Taylor’s analytical solution 012008 EN Xuanyou Gong Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroki Suzuki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Toshinori Kouchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kento Tanaka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University This study focuses on the possibility that flow around vortex tubes in turbulence may resemble laminar flow, and aims to describe the characteristics of turbulent fields using analytical solutions to the governing equations. In the two-dimensional analytical Taylor solution, the velocity and pressure fields are expressed by trigonometric functions, and a structure in which counter-rotating vortices are arranged in a grid pattern is demonstrated. This solution is used to verify the accuracy of numerical analyses and is expected to contribute to a simple yet unambiguous description of turbulent fields based on vortex structures. Predictions of sub-grid scale components and validation of a coherent structure model using invariants of the velocity gradient tensor are also performed. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2950-2217 3 2 2025 Erythromelalgia presenting with posterior reversible encephalopathy syndrome: A pediatric case report 100078 EN Kengo Suzuki Department of Pediatrics, Okayama University Hospital Kazuhiro Uda Department of Pediatrics, Okayama University Hospital Mitsuru Tsuge Department of Pediatric Acute Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kyosuke Arakawa Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Shigehara Department of Pediatrics, Okayama University Hospital Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Erythromelalgia is a rare disorder characterized by erythema, warmth, and burning pain in the extremities. We report a pediatric case of erythromelalgia in a patient who developed posterior reversible encephalopathy syndrome (PRES), without any cutaneous signs. Case presentation: A previously healthy 12-year-old girl presented to our pediatric clinic with burning extremity pain that had persisted for 6 weeks. The patient was treated with analgesics; however, the pain was refractory to these agents. Seven days after the first visit, she developed afebrile seizures and was transferred to our hospital. Her initial blood pressure was 139/105 mmHg (+2.0 SD), and brain magnetic resonance imaging revealed high intensity areas in the bilateral parietal and occipital lobes, leading to a diagnosis of PRES. Her blood pressure was difficult to control with anti-hypertensive agents. Burning pain in her extremities was relieved by cooling and worsened by warming. Although erythema was not observed in her hands or legs, erythromelalgia was suspected based on the characteristic nature of her pain. Intravenous lidocaine was administered for diagnosis, which was dramatically effective. After initiating mexiletine, the burning pain in her extremities disappeared, and hypertension improved. A final diagnosis of erythromelalgia with PRES was made. Conclusion: A history of temperature-dependent pain relief and deterioration are important indicators of disease diagnosis, even if patients indicate a lack of erythema or warmth. Physicians should be aware that persistent pain due to erythromelalgia can lead to refractory hypertension and development of PRES. No potential conflict of interest relevant to this article was reported.

岡山大学農学部 Acta Medica Okayama 2186-7755 115 2026 公表学術論文等リスト　2025 13 26 EN No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構 Acta Medica Okayama 1881-5952 3 2026 ピア・AI・教員の三者協働フィードバックによるライティング授業の再設計 ―AI利用の実践報告－ 174 194 EN Mariko Uzuka Institute for Promotion of Education and Campus Life 10.18926/70120 本稿は、アカデミック・ライティング授業におけるピア・AI・教員のそれぞれの役割と利用順序（自分→ピア→AI→（省察）→教員）を組み込んだ三者協働モデルを設計し、2024～2025年度に実践した内容を報告する。授業後の学生アンケートでは、AIの即時性・精緻化が評価される一方、依存や有効性の限界に関する懸念も表明された。成績分布においては、AI導入後に下位層が縮小し、学習成果の底上げが示唆された。また、AI誤用や濫用を防ぐには、教室内で建設的な利用法の具体的な指導（例：例文より診断的フィードバックを重視、AI提案の採否理由のメタ記述）が効果的であった。これらの結果から、AIの利点を活かしつつ、学生の判断を中心に据えるライティング授業設計の有効性と課題を提示する。 No potential conflict of interest relevant to this article was reported.

岡山大学教育推進機構 Acta Medica Okayama 1881-5952 3 2026 「知の探研」× 多文化共修 ―オンライン授業再構築の試み― 145 154 EN Yumiko YAMAMOTO Faculty of General and Global Studies (GDP), Okayama University Kha Manh NGUYEN Discovery Program for Global Learners, Okayama University 10.18926/70118 岡山大学では2025年4月入学生から新カリキュラムがスタートした。学士課程改革の一環として導入されたのが全学共通・課題探究科目「知の探研」である。本稿では，新入生対象科目である「知の探研」を，海外生を含むグローバル・ディスカバリー・プログラム生向けに英語で “Inquiries of Knowledge” として開講した初年度の取り組みを報告する。とりわけオンデマンド型オンライン授業を, 本学が推進する多文化共修の視点で再構築するにあたり，教材を単に英訳するのではなく, オンライン環境においても協働学習を実現する工夫や，言語的・文化的配慮の統合が不可欠であることを明らかにする。 No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2212-4292 71 2025 A cross-sectional study of the gut microbiota associated with urinary and serum equol production status in a general population of Japanese men 107048 EN Yukiko Okami NCD Epidemiology Research Center, Shiga University of Medical Science Hisatomi Arima Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University Shigeki Bamba Department of Fundamental Nursing, Shiga University of Medical Science Fu Namai Graduate School of Agricultural Science, Tohoku University Keiko Kondo NCD Epidemiology Research Center, Shiga University of Medical Science Yuki Ideno Gunma University Center for Food Science and Wellness Ayumi Soejima Nutraceuticals Research Institute, R&D Headquarters, Nutraceuticals Division, Otsuka Pharmaceutical Co., Ltd. Haruna Miyakawa Nutraceuticals Research Institute, R&D Headquarters, Nutraceuticals Division, Otsuka Pharmaceutical Co., Ltd. Sayuki Torii NCD Epidemiology Research Center, Shiga University of Medical Science Hiroyoshi Segawa NCD Epidemiology Research Center, Shiga University of Medical Science Mizuki Ohashi NCD Epidemiology Research Center, Shiga University of Medical Science Megumi Kawashima NCD Epidemiology Research Center, Shiga University of Medical Science Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aya Kadota NCD Epidemiology Research Center, Shiga University of Medical Science Akira Sekikawa Department of Epidemiology, School of Public Health, University of Pittsburgh Akira Fujiyoshi Department of Hygiene, Wakayama Medical University Katsuyuki Miura NCD Epidemiology Research Center, Shiga University of Medical Science SESSA Research Group Equol is a metabolite produced by the gut microbiota from the soy isoflavone daidzein. Previous studies identified bacteria capable of converting daidzein to equol. We investigated whether equol producers among Japanese with a high soy intake contained these bacteria. We also examined differences in equol production status between urine and serum and how the gut microbiota differs between these statuses. To minimize the potential confounding effects of hormonal variability in women, this cross-sectional study analyzed 853 Japanese men. Urinary and serum isoflavones were collected in the morning after fasting and were analyzed using LC-MS/MS. By applying a finite mixture model for each log10 equol/daidzein ratio, we defined equol producers and non-producers from urine and serum. Among 669 participants with fecal microbial measurements, the 16S rRNA gene was sequenced on a MiSeq System. The cut-off values for the log10 equol/daidzein ratio were −0.94 for urine and −0.95 for serum. Equol production status in urine and serum matched in 97 %, and equol producers from urine or serum were 42 %. The microbiota was more diverse in producers than in non-producers; the genus Senegalimassilia included strains with high sequence identity (>98 %) to daidzein reductase. The family Oscillospiraceae and class Clostridia also had approximately 46 %–48 % sequence identity. The equol production status of fasting urine and serum almost matched among a general population of Japanese men. Although we did not detect a microbiota with known daidzein reductase in equol producers, several shared similar sequences; these may include equol-producing bacteria that have not yet been identified. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2590-1230 27 2025 Inscribed-type spherical speed reducer with uniform reduction ratio in all directions 106742 EN Seiya Naramura Faculty of Environmental, Life, Natural Science and Technology, Okayama University Koichi Tonegawa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University So Shimooka Faculty of Environmental, Life, Natural Science and Technology, Okayama University Tomoaki Yano Faculty of Environmental, Life, Natural Science and Technology, Okayama University Akio Gofuku Okayama Prefectural University Nagayoshi Kasashima National Institute of Advanced Industrial Science and Technology Tetsushi Kamegawa Faculty of Environmental, Life, Natural Science and Technology, Okayama University A spherical motor is an actuator that can generate rotational motion about all three orthogonal axes. However, it is difficult to obtain high output torque from most electromagnetic spherical motors, primarily due to limitations inherent in electromagnetic actuators, such as restricted magnetic force and thermal constraints. Since its torque cannot be increased using planar gears, spherical speed reducers that transmit rotational torque along three orthogonal axes through sphere-to-sphere contact are required. One major limitation of conventional spherical speed reducers is that their size increases significantly as the reduction ratio becomes higher. To address this issue, we propose a novel inscribed-type spherical speed reducer, in which the deceleration mechanism is integrated within the output sphere. This configuration enables a more compact design, reducing the overall size to approximately half that of conventional designs. To predict the angular velocity and transmitted torque, theoretical models for the rotation and torque transmission of the speed reducer were developed. According to the proposed model, the reduction ratio of the spherical speed reducer is 1/3. To verify the validity of these models, experiments were conducted to measure angular velocity and torque. The theoretical results agreed well with the experimental results. In addition, the theoretical torque exhibited an average relative error of 1.63 % compared to the experimental result. Therefore, it was confirmed that the rotation and torque transmission models were valid. These results demonstrate that a reduction ratio can be obtained in all directions of the 3-DOF of the spherical speed reducer, unlike conventional 1-DOF reducers. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1865-1380 19 1 2026 Association of Wet-Bulb Globe Temperature with heat-related illness hospitalizations in Japan: a time-stratified, case-crossover study 11 EN Yuka Yamamura Department of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Fumiya Sasai Department of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Kohei Tokioka Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Jun Kanda Emergency and Critical Care Medicine, Nippon Medical School Musashikosugi Hospital Shoji Yokobori Department of Emergency and Critical Care Medicine, Nippon Medical School Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Takashi Yorifuji Department of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences Background Heat-related illnesses are a serious public health concern and are exacerbated by global warming. Wet-Bulb Globe Temperature (WBGT) is widely used as a heat stress indicator, but its clinical impact remains unclear. This study aimed to investigate the association between hourly variations in WBGT and the incidence of hospitalizations for heat-related illness in Japan using a nationwide database. By incorporating individual-level clinical data and performing stratified analyses, we sought to provide a more granular understanding of how heat exposure affects the risk of heat-related illness requiring hospitalization. Methods We conducted a time-stratified, case-crossover study using data collected from July to September in 2020 and 2021 in the Heatstroke STUDY registry. The inclusion criteria were patients registered in the Heatstroke STUDY registry, specifically hospitalized patients with heat-related illness who were transported to participating hospitals during the study period. Hourly WBGT values were assigned based on the nearest monitoring station to each hospital. Conditional logistic regression and distributed lag models were used to estimate associations between WBGT and the risk of hospitalization. Results A total of 1,653 heat-related illness hospitalizations were analyzed. The mean patient age was 67.9 years; 67.6% were male. Each 1 °C increase in WBGT at onset (hospital arrival) was associated with a significantly increased risk of hospitalization (OR 1.10, 95% CI: 1.05–1.15). The cumulative effect over the prior six hours was also significant (OR 1.56, 95% CI: 1.50–1.62). Compared with WBGT < 25 °C, adjusted ORs were 3.39 (25–27 °C), 8.81 (28–30 °C), and 22.10 (≥ 31 °C). Stratified analyses suggested stronger associations among several subgroups; however, only patients with mental disorders showed statistically significant effect modification, whereas elevated WBGT posed a risk across all groups. Conclusions Higher WBGT levels were associated with an increased risk of heat-related hospitalization. Although the effect appeared greater in some subgroups, only patients with mental disorders demonstrated statistically significant effect modification, suggesting elevated WBGT confers risk broadly. 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 Association of Carboxyhemoglobin With Severity and Outcomes in Hypothermic Patients: A Retrospective Cohort Study e97962 EN Yuya Miyoshi Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Introduction Carboxyhemoglobin (COHb), an endogenous marker of carbon monoxide production mediated by heme oxygenase-1, may reflect physiological stress responses in critically ill patients. However, its clinical relevance in accidental hypothermia remains unclear. Methods We conducted a single-center retrospective cohort study of adult patients admitted to the emergency ICU with accidental hypothermia between January 1, 2019, and March 31, 2025. Patients were categorized into low- and high-COHb groups based on median COHb levels upon emergency department arrival. Associations between COHb levels, disease severity (Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores), and 28-day mortality were analyzed using regression models adjusted for clinical confounders. Results Among the 88 patients, who had a median admission temperature of 28.7°C, 45 were classified into the low-COHb group and 43 into the high-COHb group, based on a median COHb level of 0.3%. Lower COHb levels on admission were significantly associated with higher APACHE II scores (β = −4.20; 95% CI, −7.56 to −0.85), but not with SOFA scores. Admission and minimum COHb levels were not associated with 28-day mortality. However, higher maximum COHb levels within the first 24 hours were independently associated with lower 28-day mortality (adjusted OR, 0.17; 95% CI, 0.023 to 0.93). Conclusions Lower COHb levels were associated with greater disease severity, and higher maximum COHb levels were associated with lower 28-day mortality. COHb may reflect systemic stress in accidental hypothermia, but its prognostic value appears limited. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1201-9712 164 2026 Global trends in Clostridioides difficile infection–related mortality, 2001-2023: An observational study 108315 EN Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Yoshito Nishimura Division of Hematology/Oncology, Mayo Clinic Ko Harada Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai Maki Yamamoto Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsuaki Takeda Quynh Thi Vu Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keith Pardillada Belangoy Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hanane Ouddoud Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: Clostridioides difficile infection (CDI) is a major public health concern, particularly in aging populations. The aim of this study was to evaluate global trends in CDI-related mortality to inform sustainable and cost-effective management strategies. Methods: We conducted an observational study using mortality data from the World Health Organization (WHO) database spanning 2001 to 2023. Sixty-three countries with satisfactory data quality and at least 12 years of data between 2001 and 2023 were included. Crude and age-standardized CDI-related mortality rates per 1,000,000 individuals were calculated after stratification by age, sex, WHO region, and sociodemographic index (SDI). Global trends were analyzed using locally weighted regression. Results: The global age-standardized CDI-related mortality rate was 0.76 per 1,000,000 individuals in 2001, peaked at 4.08 in 2010, and declined to 2.44 in 2023. The most notable downward trends were observed in the Americas and high-SDI countries. These improvements may reflect the impact of multidisciplinary efforts in CDI prevention and management. Conclusions: Although CDI-related mortality has declined globally over the past decade, the disease remains a significant threat, especially in older populations. Ongoing global efforts are essential to further reduce CDI-related deaths. No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 12 2025 Streptococcal Toxic Shock Syndrome Following Intestinal Obstruction in a Patient With Crohn’s Disease e100138 EN Ayano Nishio Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Hospital Toshihiro Inokuchi 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 Yuki Aoyama 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 Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kohei Oguni Department of Infectious Diseases, Okayama University Hospital Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuto Matsuoka Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomoyuki Kanazawa Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Streptococcal toxic shock syndrome (STSS) is a rare, life-threatening complication of invasive group A streptococcal (iGAS) infections. We report the case of a 24-year-old woman with Crohn's disease receiving immunosuppressive therapy who developed STSS following intestinal obstruction. On day 2, she developed fever, altered mental status, hypoxemia, erythema, and hypotension. Chest CT revealed bilateral pulmonary infiltrates, and blood cultures grew emm1-positive M1UK Streptococcus pyogenes, confirming STSS. Early multidisciplinary intervention resulted in rapid recovery without sequelae. This case emphasizes the importance of considering iGAS-induced STSS in septic shock, especially in immunocompromised patients, and highlights the need for prompt recognition and treatment. 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. 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. 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. 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 2813-2203 5 1 2025 A Threshold Selection Method in Code Plagiarism Checking Function for Code Writing Problem in Java Programming Learning Assistant System Considering AI-Generated Codes 2 EN Perwira Annissa Dyah Permatasari Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mustika Mentari Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Safira Adine Kinari Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Soe Thandar Aung Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Htoo Htoo Sandi Kyaw Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Khaing Hsu Wai Graduate School of Engineering Science, Akita University To support novice learners, the Java programming learning assistant system (JPLAS) has been developed with various features. Among them, code writing problem (CWP) assigns writing an answer code that passes a given test code. The correctness of an answer code is validated by running it on JUnit. In previous works, we implemented a code plagiarism checking function that calculates the similarity score for each pair of answer codes based on the Levenshtein distance. When the score is higher than a given threshold, this pair is regarded as plagiarism. However, a method for finding the proper threshold has not been studied. In addition, AI-generated codes have become threats in plagiarism, as AI has grown in popularity, which should be investigated. In this paper, we propose a threshold selection method based on Tukey’s IQR fences. It uses a custom upper threshold derived from the statistical distribution of similarity scores for each assignment. To better accommodate skewed similarity distributions, the method introduces a simple percentile-based adjustment for determining the upper threshold. We also design prompts to generate answer codes using generative AI and apply them to four AI models. For evaluation, we used a total of 745 source codes of two datasets. The first dataset consists of 420 answer codes across 12 CWP instances from 35 first-year undergraduate students in the State Polytechnic of Malang, Indonesia (POLINEMA). The second dataset includes 325 answer codes across five CWP assignments from 65 third-year undergraduate students at Okayama University, Japan. The applications of our proposals found the following: (1) any pair of student codes whose score is higher than the selected threshold has some evidence of plagiarism, (2) some student codes have a higher similarity than the threshold with AI-generated codes, indicating the use of generative AI, and (3) multiple AI models can generate code that resembles student-written code, despite adopting different implementations. The validity of our proposal is confirmed. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2079-9292 14 24 2025 An AI-Driven System for Learning MQTT Communication Protocols with Python Programming 4967 EN Zihao Zhu Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Htoo Htoo Sandi Kyaw Department of Information and Communication Systems, Okayama University I Nyoman Darma Kotama Department of Information and Communication Systems, Okayama University Anak Agung Surya Pradhana Department of Information and Communication Systems, Okayama University Alfiandi Aulia Rahmadani Department of Information and Communication Systems, Okayama University Noprianto Department of Information and Communication Systems, Okayama University With rapid developments of wireless communication and Internet of Things (IoT) technologies, an increasing number of devices and sensors are interconnected, generating massive amounts of data in real time. Among the underlying protocols, Message Queuing Telemetry Transport (MQTT) has become a widely adopted lightweight publish–subscribe standard due to its simplicity, minimal overhead, and scalability. Then, understanding such protocols is essential for students and engineers engaging in IoT application system designs. However, teaching and learning MQTT remains challenging for them. Its asynchronous architecture, hierarchical topic structure, and constituting concepts such as retained messages, Quality of Service (QoS) levels, and wildcard subscriptions are often difficult for beginners. Moreover, traditional learning resources emphasize theory and provide limited hands-on guidance, leading to a steep learning curve. To address these challenges, we propose an AI-assisted, exercise-based learning platform for MQTT. This platform provides interactive exercises with intelligent feedback to bridge the gap between theory and practice. To lower the barrier for learners, all code examples for executing MQTT communication are implemented in Python for readability, and Docker is used to ensure portable deployments of the MQTT broker and AI assistant. For evaluations, we conducted a usability study using two groups. The first group, who has no prior experience, focused on fundamental concepts with AI-guided exercises. The second group, who has relevant background, engaged in advanced projects to apply and reinforce their knowledge. The results show that the proposed platform supports learners at different levels, reduces frustrations, and improves both engagement and efficiency. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Development of a Stroke Discharge Support Evaluation Scale for Ward Nurses in Acute Care Hospitals 17 30 EN Hideki Yano Department of Nursing, Faculty of Human Health Sciences, Niimi University Yoko Takahata Graduate School of Health Sciences, Okayama University Takeshi Yamaguchi Faculty of Nursing, Shikoku University Shinya Saito Graduate School of Health Sciences, Okayama University Original Article 10.18926/AMO/70069 This study aimed to develop a scale enabling nurses to objectively evaluate their own stroke discharge support, as a basis for enhancing its overall effectiveness. A draft scale was created based on a literature review, and consisted of a 51-item, 5-point Likert-type questionnaire administered to ward nurses engaged in stroke discharge support at acute care hospitals. Factor analysis was performed to refine the scale. Construct validity was assessed using the known-groups method, and reliability was evaluated through internal consistency analysis. The resulting Stroke Discharge Support Evaluation Scale comprises 29 items across 5 factors, each rated on a 5-point Likert scale. Analysis of the data collected from 237 valid responses demonstrated good internal consistency and supported the scale’s construct validity. The Stroke Discharge Support Evaluation Scale is a reliable and valid tool enabling ward nurses in acute care hospitals to evaluate their own stroke discharge support. No potential conflict of interest relevant to this article was reported.

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

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 デヴィッド・グレーバー著酒井隆史訳『啓蒙の海賊たち　あるいは実在したリバタリアの物語』 286 288 EN Mikako SAWAYAMA 新刊紹介 (New Book) 10.18926/70066 No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 大知聖子著『計量的分析を用いた北魏史研究』 279 285 EN Hirokazu HASEGAWA 書評 (Book Review) 10.18926/70065 No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 犬養木堂記念館所蔵末松謙澄宛伊東巳代治書簡 273 278 EN Masayoshi MAEDA 資料紹介 (Materials and data) 10.18926/70064 No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 備陽国学記録（五） 170 272 EN Katsunao KURACHI 資料紹介 (Materials and data) 10.18926/70063 No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 補論：歴史学と生成AI 163 169 EN Seiko OCHI 展望 (Perspectives) 10.18926/70062 No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 津島岡大遺跡の発見－歴史における趨勢と偶然－ 156 162 EN Takahiro NOZAKI 展望 (Perspectives) 10.18926/70061 No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 Materiality, Making and Movement : A commentary 153 155 EN Masakazu TANAKA Faculty of International Fashion, PROFESSIONAL INSTITUTE OF INTERNATIONAL FASHION 特集：Sacred Objects in Religions (Special Issue: Sacred Objects in Religions) 10.18926/70060 No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 Depicting Buddha : Practice, Prescription and Perception 134 152 EN Shijun ZHANG Department of Sociology & Institute of Sociology and Anthropology, Peking University 特集：Sacred Objects in Religions (Special Issue: Sacred Objects in Religions) 10.18926/70059 Tibetan thangka refers to a genre of pictorial art widely produced across the Tibetan cultural region since the 11th century. Although scroll painting is its most common form, thangkas are also created through embroidery, appliqué, and brocade weaving. The subjects depicted encompass a wide range of themes within Tibetan Buddhism and the Bön religion, including various Buddhas, bodhisattvas, deities, monks, mandalas, as well as astronomical and medical knowledge. Within Tibetan religious beliefs, thangkas are not merely visual representations; they are venerated as supports of Buddha (Tib. sku rten), understood as physical embodiments of divine presence. At the same time, the creation and veneration of thangka constitute a rich aesthetic tradition in which artists repeatedly integrate realist elements into this sacred canvas. This paper offers a micro anthropological examination (Tanaka 2005; 田中 2006) of the depiction of thangka as a practice oscillating between inscribing the canonical and drawing the real. Through critically engaging with the theory of agency of art (Gell 1998), and the analysis of writing and drawing (Ingold 2017), this study examines the dialectical relationship between rendering sacred images and depicting worldly reality, and how such practices unfold in the tension between prescriptive authority and embodied perception. No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 “God” is Coming to My Home : Catholic Images and the Sacred in the Case of a Rural Village in Western Mexico 115 133 EN Naomi KAWAMOTO Research Institute for the Dynamics of Civilizations, OKAYAMA UNIVERSITY 特集：Sacred Objects in Religions (Special Issue: Sacred Objects in Religions) 10.18926/70058 This paper aims to clarify the dynamic aspect of the sacred that the religious image is imbued with, focusing on a Catholic practice in a current rural village of western Mexico. In classical studies of the sacred, it has generally been considered disconnected from the profane and ambivalent. Other research has revealed the multi-layered nature of the sacred and its constructive aspect. In contrast, this paper will discuss a sacredness that arises from the interaction between human beings and objects, a sacredness that is both performative and intimate. Thus, this article will analyze practitioners’ everyday, contingent acts, free from formality. In conclusion, “the sacred” contains a part of the profane caused by the Catholic image going back and forth between the realms of “the sacred” and “the profane”. No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 From Festivals to the Everyday: The Circulation of Kumade at the Tori no Ichi at Hanazono Shrine 101 114 EN Mia TILLONEN Department of English Language and Culture, FUJI WOMEN’S UNIVERSITY 特集：Sacred Objects in Religions (Special Issue: Sacred Objects in Religions) 10.18926/70057 Every year in November, the Tori no Ichi festival draws huge crowds to the grounds of Hanazono Shrine in Shinjuku, Tokyo. The festival is centered around the buying and selling of kumade, or good luck rakes. These bold and colorful objects function as engimono, or good luck charms, purchased for business prosperity or home safety. This study explores the circulation and itinerary of kumade at the Tori no Ichi festival by analyzing the performances surrounding them. While previous scholarship on engimono has focused on their roles in domestic settings or disposal rituals, this research approaches them in situ at the festival. The study shows that these objects bridge the festival and the everyday, connecting people to the event and the sacred site through a dynamic network of social, spatial, and ritual practices. The research draws on fieldwork and in-depth interviews conducted at Hanazono Shrine between 2020 and 2024. No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 Generating Sacredness in the Domestic Sphere: Wedding Rituals and the Navarātri Kolu Festival in South India 82 100 EN Mayumi IIZUKA JapanTakasaki University of Commerce 特集：Sacred Objects in Religions (Special Issue: Sacred Objects in Religions) 10.18926/70056 This article examines how domestic sacredness is dynamically generated, negotiated, and undone within South Indian Brahmin households. Based on ethnographic analysis of the wedding first-night ritual and the Navarātri kolu festival, the study shows how ritual doubling—exemplified by the marappācci dolls as symbolic doubles of the bridal couple—and the circulation of miniature utensils link life-cycle rites with annual festivals. The kolu’s stepped display condenses cosmological hierarchies while activating gendered forms of ritual practice, auspiciousness (maṅgalam) and purity (śuddham). Everyday acts such as sweeping threshold, sparkling water, drawing kolam, and lighting lamps function as “religious profane” practices that continually remake the boundaries between the mundane and the sacred. Digital sharing and online kolu competitions further extend domestic sacredness into dispersed social networks. By foregrounding materiality, gender, purity, and the ephemerality of ritual arrangements, the article demonstrates that domestic sacredness is a plural, fragile and continually renewed process of making and unmaking. No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 Introduction 74 81 EN Naomi KAWAMOTO RIDC, Okayama University 特集：Sacred Objects in Religions (Special Issue: Sacred Objects in Religions) 10.18926/70055 No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 Area Studies のなかの「地域史」研究ー歴史研究者、J・W・ホールから見るミシガン大岡山分室と瀬戸内海総合研究会ー 54 73 EN Shizue OSA Kobe University 研究ノート (Research note) 10.18926/70054 During the late Allied occupation and the 1950s, the University of Michigan’s Center for Japanese Studies established a field station in Okayama, where American scholars conducted rural research. This article examines the challenges of academic research under occupation and analyzes how such research was organized through specific actors and institutional arrangements, with particular attention to its intersection with the academic knowledge of the host institution, Okayama University. Focusing on the historian John W. Hall, it traces the activities of the Michigan field station and explores its interactions with Okayama University and the Seto Inland Sea Cultural Research Group. The article argues that while archival research—understood as a form of fieldwork—facilitated collaborative research, differing conceptions of rural society constituted a critical point of divergence in the production of scholarly knowledge. No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 「新羅村落文書」に記された村の比定地 ―西原京所属の村（いわゆるＤ村）の検討― 40 53 EN Nana MURAKAMI Research Institute for the Dynamics of Civilizations, Okayama University 研究ノート (Research note) 10.18926/70053 The Silla Village Register is a fragmentary record from the Unified Silla period that details the economic conditions of villages under the jurisdiction of small capitals (小京) and local counties (郡 / 県). In analyzing this register, it is essential to consider the geographical conditions of the locations; however, the exact locations of the villages have long remained unidentified in previous studies. Therefore, this study builds on the readings proposed by Choi Kyŏng-sŏn ( 최 경 선 ) and examines official histories and geographical texts from the Chosŏn dynasty, as well as topographic maps from the early 20th century. As a result, this paper proposes a concrete candidate for the location of one of the four villages under the jurisdiction of Sŏwŏn-gyŏng (西原京), commonly referred to as Village D. It has been clarified that Village D can be read as " 西原京□椒子村" and it is highly likely to correspond to present-day Chojŏng-ri, Naesu-ŭp, Heungdeok-gu, Cheongju City (清州市清原区内秀邑椒井里). It was also found that Village D’s characteristic of having few rice paddies and a high proportion of upland field cultivation closely matches the actual local geographical conditions, which are characterized by limited water resources. No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 島根県猪目洞窟遺跡出土人骨の年代・食性・遺伝的特徴 20 39 EN Hideaki KANZAWA-KIRIYAMA Division of Human Evolution, Paleontology and Anthropology, National Museum of Nature and Science, Tsukuba City, Ibaraki Prefecture Mai TAKIGAMI Division of Human Evolution, Paleontology and Anthropology, National Museum of Nature and Science, Tsukuba City, Ibaraki Prefecture Tsuneo KAKUDA Department of Legal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi Leo SPEIDEL Center for Interdisciplinary Theoretical and Mathematical Sciences, RIKEN Garrett HELLENTHAL Department of Genetics, Evolution and Environment, University College London Genetics Institute (UGI), University College London Nancy BIRD Department of Genetics, Evolution and Environment, University College London Genetics Institute (UGI), University College London Yousuke KAWAI Genome Medical Science Project, National Institute of Global Health and Medicine, National Institute for Health Security NCBN Controls WGS Consortium Minoru SAKAMOTO National Museum of Japanese History Yuichi KAMEDA Division of Human Evolution, Paleontology and Anthropology, National Museum of Nature and Science, Tsukuba City, Ibaraki Prefecture Noboru ADACHI Department of Legal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi Ken-ichi SHINODA National Museum of Nature and Science Naruya SAITOU National Institute of Genetics Tatsuhiko HAMADA Research Institute for the Dynamics of Civilizations, Okayama University 論文 (Research article) 10.18926/70052 This paper reports on the integrative research findings of the human bones excavated from the Inome Cave Site in Shimane Prefecture, based on dietary estimation using carbon and nitrogen isotope analysis, radiocarbon dating, and whole genome analysis. The dates of the analyzed human bones span a wide range, from the Middle to Late Kofun period, the Nara period to the Early Heian period, and the Middle to Late Heian period, indicating that the Inome Cave Site was continuously used as a burial place. Dietary habits were a mixture of C3 resources (C3 plants and terrestrial animals that consumed C3 plants) and marine resources, with individual variations in the intake of marine and terrestrial resources. A correlation was observed between differences in dietary habits and individual variations in the Jomon ratio in the nuclear genome, with individuals who consumed higher amounts of marine resources tending to have a higher Jomon ratio. This suggests that individuals with different backgrounds were buried in the same site due to interactions with surrounding settlements. No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 日本における「ロシアかぜ」流行の社会史的分析 ―1889 -1891 年パンデミックと日本社会― 1 19 EN Atsushi KAWAUCHI Uehiro Disaster Risk Reduction Research Division, International Research Institute of Disaster Science (IRIDeS), TOHOKU UNIVERSITY 論文 (Research article) 10.18926/70051 This study offers a social-historical analysis of the “Russian flu” pandemic in Japan (1889–1891). Due to scarce statistical data, the study relies primarily on contemporary newspapers and magazines. It identifies two distinct epidemic waves: the first in spring-summer 1890, and the second from late 1890 to spring 1891. The first wave, though widespread, was overshadowed by a concurrent cholera epidemic and caused relatively few deaths, whereas the second wave was far more lethal and generated widespread fear. At the time, influenza remained an “unknown disease”, with unclear etiology and no established treatments. People responded with diverse measures, from purchasing patent medicines and using folk remedies to symbolic practices such as "disease naming" (osome-kaze). The crisis also renewed attention to historical records of earlier influenza-like epidemics in Japan. In contrast, by the time of the later “Spanish flu” pandemic, advances in bacteriology had already rendered influenza a medically defined disease. This comparison highlights how shifting medical knowledge shaped societal responses. The findings not only corroborate previous excess-mortality analyses but also provide new historical insights into how societies have historically confronted pandemics. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2769-2558 5 1 2026 Cardiogenic cerebral infarction after Takotsubo cardiomyopathy in a patient with catatonia: A case report e70285 EN Masaki Fujiwara Department of Neuropsychiatry, Medical Development Field, Okayama University Yuto Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Osawa Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center Shinji Sakamoto Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Kodama Okayama Psychiatric Medical Center Background: Takotsubo cardiomyopathy (TTC) is a transient cardiac condition often triggered by an emotional or physical stress. TTC usually has a benign clinical course with full recovery. However, in rare cases, TTC is complicated by cardiogenic shock, left ventricular rupture, or ventricular thrombus. We report a case of a patient with catatonia who developed TTC and subsequently experienced extensive cerebral infarction. Case Presentation: A 71-year-old woman with no prior psychiatric history was admitted for catatonia following a suicide attempt. During hospitalization, she exhibited electrocardiography (ECG) abnormalities and elevated D-dimer levels. Transthoracic echocardiography revealed apical hypokinesis and basal hyperkinesis, consistent with TTC, along with an intraventricular thrombus. Cardiovascular CT angiography confirmed normal coronary arteries. She was diagnosed with TTC complicated by left ventricular thrombus and deep vein thrombosis. Anticoagulant therapy was initiated. Despite improvement in catatonia with lorazepam, she developed right hemiplegia and aphasia on Day 5 due to cardiogenic cerebral infarction from thromboembolism. Thrombolytic therapy was not indicated, and conservative treatment was provided. Although cardiac function normalized by Day 16, she was left with severe neurological deficits. Conclusion: The case highlights the diagnostic challenges of TTC in non-communicative psychiatric patients and the potential for severe complications. Psychiatrists need to be aware of the development of TTC as a serious physical complication in patients with catatonia. No potential conflict of interest relevant to this article was reported.

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

eLife Sciences Publications, Ltd Acta Medica Okayama 2050-084X 14 2026 Dorsoventral-mediated Shh induction is required for axolotl limb regeneration RP106917 EN Sakiya Yamamoto Okayama University, Graduate School of Environmental, Life, Natural Science and Technology Saya Furukawa Okayama University, Graduate School of Environmental, Life, Natural Science and Technology Ayaka Ohashi Okayama University, Graduate School of Environmental, Life, Natural Science and Technology Mayuko Hamada Okayama University, Graduate School of Environmental, Life, Natural Science and Technology Akira Satoh Okayama University, Graduate School of Environmental, Life, Natural Science and Technology Axolotls (Ambystoma mexicanum) exhibit a remarkable ability to regenerate limbs. Classical experiments have suggested that contact between cells derived from distinct orientations—dorsal, ventral, anterior, and posterior—within the regenerating blastema is necessary for accurate limb pattern formation. However, the molecular basis for this requirement has remained largely unknown. Here, we demonstrate that both dorsal and ventral tissues are required for limb formation via induction of Shh expression, which plays a crucial role in limb patterning. Using the accessory limb model, we induced position-specific blastemas lacking cells derived from a single orientation (anterior, posterior, dorsal, or ventral). Limb patterning occurred only in blastemas containing both dorsal- and ventral-derived cells. We further observed that Shh expression requires dorsoventral contact within a blastema, highlighting the necessity of dorsoventral contact for inducing Shh expression. Additionally, we identified WNT10B and FGF2 as dorsal- and ventral-mediated signals, respectively, that create the inductive environment for Shh expression. Our findings clarify the role of dorsal and ventral cells in inducing Shh, a mechanism that has rarely been studied in the context of limb regeneration and pattern formation. This model provides new insights into how cells with different positional identities drive the regeneration process. No potential conflict of interest relevant to this article was reported.

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

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 裏表紙・英文目次 EN No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 奥付 EN No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 菊舎の太宰春台詩受容について (41) (58) EN MENGHUAN LI 10.18926/70034 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 「有翼の天女図」十三考― 竹内栖鳳による東本願寺御影堂門の天井画とその周辺 ― (21) (39) EN Yuko TATSUNO 10.18926/70033 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 『論語集注』訳注（子罕第九　（一）） (1) (20) EN Luyi SUN 10.18926/70032 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 日本語版 The Passive Aggression Scaleの作成および信頼性と妥当性の検討 245 260 EN Ayaka SHIGETOU Young-Ok Lim Kyung-Hyun Suh Kyoko SUMIOKA 10.18926/70031 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 台湾の工業及びサービス業をめぐる低賃金及び賃金格差問題について 225 244 EN HONG TING CHIANG 10.18926/70030 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 日本の一地方の中小企業の貿易・投資相談事例分析― アクションリサーチ及びショーン（1983）の「省察的実践論」を活用した直近三年間の相談事例の現況分析の試み ― 205 224 EN Masaaki NAGAMITSU 10.18926/70029 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 「じゃあ」との共起から見た日本語の勧誘文― 談話構造に着目して ― 187 204 EN Lizhong XING 10.18926/70028 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 科学を担う他者たち：清末科学小説における親縁と鏡像の表象分析 169 185 EN XIAOXUAN WU 10.18926/70027 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 漢語接尾辞「派」による派生語について― 前接語が固有名詞の場合 ― 157 168 EN XUE LI 10.18926/70026 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 『本朝小説』における引用の分析― 引用内容と文脈の関連性について ― 139 156 EN JIAJIA LIU 10.18926/70025 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 現代日本語における「わりに（は）」の用法について 129 137 EN WENHUA YANG 10.18926/70024 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 外国人技能実習生のキャリア形成と日本語学習の意味付け― 日本でキャリアを継続するベトナム人技能実習生の語りから ― 109 128 EN Ngoc Bich Tran HOANG 10.18926/70023 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 現代日本語の会話における「で」のフィラー的な使用について 89 107 EN YANG LIU 10.18926/70022 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 動作の主体を主語とする難易文について 71 88 EN HUIXIN SUN 10.18926/70021 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 フッサールの発生的現象学に関する先行研究の整理と比較検討―― 方法論的問題を中心に ―― 51 69 EN Daisuke SATO 10.18926/70020 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 ライプニッツの「人間学」―『定義集』の叙述を中心に― 31 50 EN Tsuyoshi MATSUDA 10.18926/70019 No potential conflict of interest relevant to this article was reported.

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 卑弥呼の残像（下）――明清通俗文学作品に描かれた日本人女性と日本イメージ―― 19 29 EN Toru YUSA 10.18926/70018 No potential conflict of interest relevant to this article was reported.

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

岡山大学大学院社会文化科学研究科 Acta Medica Okayama 1881-1671 60 2025 表紙 EN No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0041-1132 2026 Pediatric autologous peripheral blood stem cell collection without heparin using a highly concentrated sodium citrate anticoagulant: A retrospective comparison with standard ACD-A EN Keiko Fujii Department of Hematology, Okayama University Hospital Wataru Kitamura Department of Hematology, Okayama University Hospital Kana Washio Department of Pediatrics, Okayama University Hospital Kazuhiro Ikeuchi Department of Hematology, Okayama University Hospital Joji Shimono Department of Hematology, Okayama University Hospital Hiroyuki Murakami Department of Hematology, Okayama University Hospital Fumio Otsuka Division of Clinical Laboratory, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Okayama University Hospital Nobuharu Fujii Department of Hematology, Okayama University Hospital Background: Heparin combined with sodium citrate has been used in leukocytapheresis for pediatric patients. Since 2022, we have performed leukocytapheresis using a highly concentrated sodium citrate solution (HSC, 5.32%) instead of acid citrate dextrose solution A (ACD-A). We conducted this study to determine whether HSC use reduces run time and the total amount of anticoagulant solution in children. Study Design and Methods: We retrospectively analyzed data from consecutive autologous peripheral blood stem cell harvests (auto-PBSCHs) between June 2012 and May 2025, including patient characteristics, mobilization methods, protocol used, anticoagulant type, run time, total anticoagulant solution volume, and collection efficiency. Results: Auto-PBSCH was performed using the mononuclear cell collection (MNC) protocol in 28 procedures and the continuous MNC protocol in 20 procedures. ACD-A was used in 35 procedures and HSC in 13. The run time was significantly shorter (204 [range, 117–302] vs. 157 min [range, 103–227], p = .02) in the HSC group and also confirmed in multivariable regression analysis (coefficient, −55.6; 95% confidence interval, −106.2 to −5.04; p = .03). In a subgroup analysis of cMNC procedures, CD34+ collection efficiency showed a strong negative correlation with the proportion of run time devoted to establishing the initial interface (r = −.73, p = .0003). Conclusion: Delays in establishing the initial interface can reduce the duration of the effective MNC collection phase and may negatively affect collection efficiency. Careful attention to the initial interface phase is therefore warranted when using HSC. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 1756-2848 19 2026 Clinical efficacy and safety of endoscopic ultrasound-guided ablation therapies for pancreatic neuroendocrine tumors: a systematic review and meta-analysis EN Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Hospital Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Hospital Yasuto Takeuchi Department of Gastroenterology and Hepatology, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Background: Pancreatic neuroendocrine tumors (pNETs) are rare; however, they are increasingly being detected. Although surgical resection remains the standard treatment, its invasiveness has prompted interest in less invasive alternatives, particularly for small non-functional pNETs (NF-pNETs) and insulinomas. Objectives: To evaluate the clinical efficacy and safety of endoscopic ultrasound-guided ethanol injection (EUS-EI) and radiofrequency ablation (EUS-RFA) for pNETs. Design: A systematic review and meta-analysis. Data sources and methods: A literature search of PubMed, MEDLINE, and Google Scholar was conducted (April 2005–April 2025). Studies were eligible if they reported clinical outcomes of EUS-EI or EUS-RFA in adult patients with insulinomas or NF-pNETs. The primary endpoints were clinical success (short-term symptom resolution or radiological response) and adverse event (AE) rates. Data were pooled using a random-effects model. Results: Twenty-six studies were included in the meta-analysis. For insulinomas, the pooled clinical success rate was 77% (95% confidence interval (CI), 59–88) for EUS-EI and 95% (95% CI, 89–97) for EUS-RFA. The pooled incidence of total AEs was 32% (95% CI, 17–51) for EUS-EI and 25% (95% CI, 15–39) for EUS-RFA. For NF-pNETs, the pooled clinical success rates were 76% (95% CI, 54–90) for EUS-EI and 85% (95% CI, 74–92) for EUS-RFA, and the pooled incidence of total AEs was 27% (95% CI, 20–35) and 26% (95% CI, 17–38), respectively. The most common moderate or severe AEs were pancreatitis in 12 patients (7.6%) after EUS-EI, and pancreatic fluid collection in 4 patients (1.9%) and pancreatic duct stricture in 3 patients (1.4%) after EUS-RFA. One fatal case occurred in a 97-year-old patient following EUS-RFA. Conclusion: Both EUS-EI and EUS-RFA are effective, relatively safe, and minimally invasive treatment options for pNETs. However, severe AE can occur, and careful patient selection and treatment indication are essential. Trial registration: Not registered. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0022-152X 62 12 2025 An Improved Synthesis of a Key Intermediate for Glycosylation of Biopterin and Its Application for the First Synthesis of Microcystbiopterin B 2021 2029 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Yuta Maeda Department of Chemistry, Faculty of Science, Okayama University Katsuya Iwasaki Department of Chemistry, Faculty of Science, Okayama University A key intermediate for the selective 2′-O-glycosylation of biopterin, N2-(N,N-dimethylaminomethylene)-1′-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]biopterin (12), was efficiently synthesized via a novel route starting from d-glucose, leading to an improved overall yield. This new pathway involves the preparation of a 5-deoxy-l-arabinose phenylhydrazone derivative (9) as a crucial intermediate in the construction of the pteridine ring. Utilizing compound 12, the first synthesis of microcystbiopterin B (4) was accomplished by glycosylation of 12 with 4,6-di-O-acetyl-2-O-(4-methoxybenzyl)-3-O-methyl-α-d-glucopyranosyl bromide (19) in the presence of silver triflate and tetramethylurea, followed by stepwise deprotection. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0008-6215 558 2025 First total synthesis of cyanopterin, a pterin glycoside isolated from a cyanobacterium 109710 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Yuta Maeda Department of Chemistry, Faculty of Science, Okayama University Kazumasa Ejiri Department of Chemistry, Faculty of Science, Okayama University The first total synthesis and structural identification of cyanopterin, a pterin glycoside isolated from the cyanobacterium Synechocystis sp. PCC 6803, has been accomplished. The synthesis was achieved by convergent coupling of three key derivatives: d-glucuronate, d-galactose, and 6-hydroxymethylpterin. An α-selective glycosylation enabled efficient construction of the glucuronate–galactose disaccharide, while subsequent β-exclusive glycosylation with the 6-hydroxymethylpterin derivative furnished the desired pterin–disaccharide glycoside. Final deprotection provided cyanopterin in its natural form, allowing confirmation of its precise structure. No potential conflict of interest relevant to this article was reported.

Japanese Society of Tribologists Acta Medica Okayama 1881-2198 20 4 2025 Tribological Properties of Amorphous-SiC-Based Coatings on Al2O3 Substrates in Normal Saline 212 219 EN Tadashi Shiota Faculty of Environmental, Life, Natural Science and Technology, Okayama University Daiki Taniya Graduate School of Natural Science and Technology, Okayama University Kazuma Shimazaki Graduate School of Natural Science and Technology, Okayama University Chiyu Nakano Department of Comprehensive Technical Solutions, Okayama University Yuya Omiya Faculty of Environmental, Life, Natural Science and Technology, Okayama University Masahiro Fujii Faculty of Environmental, Life, Natural Science and Technology, Okayama University Amorphous SiC (a-SiC)-based coatings containing not only Si–C bonds but also C–Si–O, C–C, and Si–O2 bonds were deposited on Al2O3 substrates via pulsed laser deposition. Sliding tests using SiC ceramic balls in normal saline revealed that the coating exhibited a low friction coefficient of 0.05-0.06 at a shorter running-in process than SiC bulk ceramic plates. The specific wear rate of the coating was also lower than that of the SiC plate. Reactive molecular dynamics simulations revealed that the C–Si–O bonds in the coating facilitated the generation of Si–O units, which contained Si–O bonds but no Si-C bonds, through tribochemical reactions with water, resulting in superior tribological properties in normal saline compared to those of SiC plates. These findings demonstrate that a-SiC-based coatings containing C–Si–O bonds are promising as low-friction and low-wear coatings for biomedical implants such as ceramic joint prostheses. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 3 2025 Prospective Evaluation of the Safety and Compression Performance of Novel Compression Denim Jeans in Healthy Volunteers and Patients With Lymphedema e80971 EN Daiki Ousaka Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kiyoshi Yamada Departments of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriko Sakano Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoe Kirino Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazumasa Miyake Department of Rehabilitation, Lymphedema Treatment Center, Kousei Hospital Takumi Takahashi Division of Business Management, Matsuoka Corporation Akihiro Matsuoka Division of Production Engineering, Matsuoka Corporation Shintaro Yamada Division of Sales, Kaihara Corporation Akira Shinaoka Department of Lymphatics and Edematology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Oozawa Department of Clinical Safety, Okayama University Hospital Objectives: The treatment of lower-extremity lymphedema, whether congenital or acquired, remains challenging. Long-term management aimed at reducing complications and maximizing quality of life is essential. Compression stockings are crucial in this management; however, their application is limited by patient experience (ease of wear, texture, breathability, and appearance). This highlights the need to evaluate alternative compression garments that maintain therapeutic efficacy while improving patient adherence. Methods: We developed a novel compression denim product (Flow plus Jeans®) using advanced sewing technology. Its baseline performance (compression ability) was evaluated by measuring pressure gradients at three points (ankle, calf, and thigh) using a mannequin-based compression testing system and compared with those of existing stockings. Thereafter, a safety assessment was conducted on healthy volunteers to evaluate potential adverse effects, including changes in lower limb circumference, signs of deep vein thrombosis (DVT) via ultrasound, and skin complications. A clinical trial in patients with lymphedema was then performed to compare its efficacy with that of conventional compression stockings. Results: Baseline performance testing with a mannequin revealed that Flow plus Jeans demonstrated compression levels and pressure gradients at three calf points comparable to those of standard compression stockings. A safety study involving nine healthy volunteers confirmed that Flow plus Jeans caused no significant changes in lower-limb circumferences after three days of wear, with no cases of DVT or skin complications. In a subsequent clinical trial involving nine female patients with lymphedema, the jeans showed non-inferiority to existing stockings concerning lower-limb circumference measurements at six points (pre-use vs. six months post-use), with patient-reported experiences assessed via questionnaires. Notably, patients reported enhanced satisfaction regarding the jeans' fashionability, which could serve as an incentive for long-term adherence. Conclusion: Our findings suggest that Flow plus Jeans represent a promising novel option for the long-term management of lymphedema, offering an alternative that balances medical efficiency with improved patient satisfaction and demonstrates safety in healthy individuals. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0022-3492 2026 A retrospective cohort study comparing periodontal regeneration using fibroblast growth factor‐2 versus autologous bone graft EN Toshiki Matsumoto Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin Nakamura Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Ito‐Shinoda Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mai Sakamoto Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayuki Ishii Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuki Nonomura Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidetaka Ideguchi Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Okubo Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Kazu Takeuchi‐Hatanaka Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Kazuhiro Omori Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yamamoto The Center for Graduate Medical Education (Dental Division), Okayama University Hospital Shogo Takashiba Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Fibroblast growth factor-2 (FGF-2) is a novel agent utilized in periodontal regeneration therapy. However, its clinical efficacy compared with autologous bone graft (ABG), a long-established treatment, remains unclear. This study aimed to compare the clinical outcomes of FGF-2 and ABG and to assess the impact of patient background factors on outcomes when using FGF-2. Methods: We collected the subjects from January 2013 to September 2023. Clinical outcomes included the vertical bone defect improvement rate (VBDIR) and the probing pocket depth improvement (PPDI). Clinical outcomes between the two groups were compared using analysis of covariance (ANCOVA), adjusting for age, sex, smoking history, and hypertension. Additionally, a multilevel linear analysis was performed to assess factors influencing outcomes in FGF-2. Results: A total of 180 sites from 141 patients (FGF-2: 150 sites; ABG: 30 sites) were evaluated. Both VBDIR and PPDI significantly improved postoperatively in both groups. There were no significant differences in clinical outcomes between FGF-2 and ABG. In FGF-2, smoking history was positively associated, while the preoperative bone defect angle (BDA) was negatively associated with clinical outcomes. Conclusions: FGF-2 might exhibit clinical outcomes comparable to those of ABG, suggesting it is a clinically viable alternative for vertical bone defects. When using FGF-2, patient-specific factors such as smoking history and preoperative BDA should be considered carefully. The name in the trial registry: A survey of clinical practice and evaluation of treatment outcomes of periodontal regenerative therapy using REGROTH at Okayama University Hospital No potential conflict of interest relevant to this article was reported.

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

The Japanese Society of Interventional Radiology Acta Medica Okayama 2432-0935 10 2025 Is Saline Sealing of Needle Tract Effective to Prevent Pneumothorax after Computed Tomography-guided Lung Biopsy? e2025-0068 EN Soichiro Okamoto Department of Radiology, Okayama University Hospital Yusuke Matsui Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Tomita Department of Radiology, Okayama University Hospital Kazuaki Munetomo Department of Radiology, Okayama University Hospital Noriyuki Umakoshi Department of Radiology, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Medical Development Field, Okayama University Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose: To evaluate the efficacy of needle tract sealing using normal saline instillation for decreasing the risk of pneumothorax after computed tomography-guided lung biopsy. Material and Methods: This retrospective, single-institution study included 391 computed tomography-guided lung biopsies performed by 12 operators between January 2022 and October 2024. After exclusion, 298 biopsies were analyzed by comparing the saline seal (n = 138) and control (n = 160) groups. A 17/18-gauge or 19/20-gauge coaxial biopsy system was used, and tract sealing was performed by instilling 1-5 mL of normal saline during the withdrawal of the introducer needle in the saline seal group; tract sealing was not performed in the control group. After 1:1 propensity score matching was performed to balance baseline characteristics, the incidences of pneumothorax and chest tube placement were compared between the two groups using Fisher's exact test. Results: After propensity score matching, 108 pairs (mean lesion size: 17 mm) were well balanced. The incidence of pneumothorax did not differ significantly between the control and saline seal groups (50.0% vs. 60.2%, respectively; p = 0.171). Similarly, the incidence of chest tube placement was not significantly different between the two groups (7.4% vs. 13.0%, respectively; p = 0.260). Conclusions: According to the propensity score-matched analysis, normal saline instillation for tract sealing did not significantly reduce the incidence of pneumothorax or chest tube placement. In our cohort, which had a high prevalence of small lesions, saline sealing alone may be insufficient to reduce post-biopsy pneumothorax risk. Hence, combined strategies require further investigation. No potential conflict of interest relevant to this article was reported.

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

Baishideng Publishing Group Inc. Acta Medica Okayama 1948-5190 17 12 2025 Endoscopic features of oral and pharyngolaryngeal papillomas and their role in distinguishing squamous cell carcinoma 110594 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Hospital Kenta Hamada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshiyasu Kono Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences BACKGROUND Oral and pharyngolaryngeal papillomas are occasionally detected during esophagogastroduodenoscopy. However, their endoscopic features have not been sufficiently investigated. AIM To distinguish oral and pharyngolaryngeal papillomas from elevated squamous carcinomas, this study examined their endoscopic features. METHODS Forty-seven patients with oral or pharyngeal papilloma participated in this study. The endoscopic characteristics of papillomas were identified by focusing on narrowband and blue laser imaging representations. RESULTS Papillomas were classified into three patterns based on their endoscopic features: Salmon roe-like polyps, polyps without capillary transparency, and pinecone-like polyps, with salmon roe-like polyps most prevalent (48.9%). We subsequently analyzed features differentiating papillomas and squamous cell carcinomas in the same region and found that squamous cell carcinomas exhibited at least one of the following three features: Uneven or absent lobulated structure, irregular morphology of capillaries, and coexistence of flat lesions. In contrast, papillomas displayed a uniform lobulated structure, homogeneous or non-visible capillaries, and an absence of flat components. When any of these characteristics were present, two endoscopic specialists evaluated the lesions for the diagnosis of squamous cell carcinoma, with sensitivities of 100% and 97.6% and specificities of 68.9% and 93.3%. CONCLUSION Understanding distinct endoscopic patterns of oropharyngeal papillomas and squamous cell carcinomas provides valuable guidance to endoscopists performing esophagogastroduodenoscopy. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 1341-321X 31 7 2025 Impact of full-time equivalent allocation on the effectiveness of antimicrobial stewardship activities: A multicenter study in Okayama, Japan 102730 EN Shiho Kajita Antimicrobial Stewardship Team, Okayama City Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Atsushi Okita Department of Surgery, Setouchi City Hospital Yuto Haruki Department of Pharmacy, Tsuyama Chuo Hospital Haruto Yamada Antimicrobial Stewardship Team, Okayama City Hospital Yasurou Inoue Antimicrobial Stewardship Team, Okayama City Hospital Tsukasa Higashionna Department of Pharmacy, Okayama University Hospital Kana Satou Division of Pharmacy, Kurashiki Central Hospital Fumihiro Torigoe Division of Pharmacy, Kurashiki Central Hospital Shinobu Iwamoto Division of Pharmacy, Okayama Kyoritsu Hospital Mika Yoshida Infection Control Team, National Hospital Organization Minami-Okayama Medical Center Yumiko Yamane Infection Control Team, National Hospital Organization Minami-Okayama Medical Center Hiroki Kenmotsu Division of Pharmacy, Okayama Saiseikai Hospital Satoru Sugimura Department of Internal Medicine, Okayama Kyoritsu Hospital Yutaka Fujiwara Infection Control Team, National Hospital Organization Minami-Okayama Medical Center Fusao Ikeda Department of Hepatology, Okayama Saiseikai Hospital Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Chikamasa Yoshida Infection Control Team, Okayama City Hospital Shinichirou Andou Infection Control Team, Okayama City Hospital Toshimitsu Suwaki Infection Control Team, Okayama City Hospital Background: Optimized administration of antimicrobial agents is critical for mitigating the emergence of antimicrobial resistance. This study aimed to elucidate the relationship between antimicrobial stewardship (AS) activities and antimicrobial prescription trends and patterns. Methods: This retrospective, multicenter, longitudinal study was conducted between April 2014 and March 2023 (9-year fiscal period). A structured, questionnaire survey, regarding institutional infrastructure and environmental parameters, service modalities provided by AS activities, resource allocation and systemic support, and data on the use of broad-spectrum antimicrobial agents, was distributed to co-investigators working at seven hospitals in Okayama, Japan. Full-time equivalent (FTE) allocation for each healthcare facility were calculated and subsequently compared among the hospitals. Temporal variations in the proportional distribution of broad-spectrum antimicrobial agents were statistically evaluated using joinpoint regression analysis. Results: Two hospitals where pharmacists were exclusively dedicated to AS activities and met the recommended FTE allocation showed a statistically significant reduction in the proportion of broad-spectrum antibiotic administration, with average annual percentage changes of −8.0 % (95 % confidence interval [CI]: −10.5 to −5.8) and −3.1 % (95 % CI: −5.5 to −0.7), respectively. In contrast, two other hospitals with full-time AS members but insufficient FTE allocation exhibited inconsistent and statistically nonuniform trends. The remaining three healthcare institutions with poorly resourced AS teams demonstrated no statistically significant trends in their broad-spectrum antimicrobial prescriptions. Conclusion: Our findings uncovered that hospitals with adequate FTE staffing metrics for AS activities exhibited statistically significant downward trends in the consumption of broad-spectrum antimicrobial agents. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2328-8957 13 1 2025 Impact of Candida Care Bundle Compliance on the Prognosis of Patients With Candidemia: A Multicenter Retrospective Cohort Study With Propensity Score Matching Analysis (2016–2023) ofaf790 EN Hidemasa Akazawa Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Toshie Higuchi Department of General Internal Medicine, Okayama Red Cross Hospital Tomoko Miyoshi Center for Medical Education and Internationalization, Kyoto University Graduate School of Medicine Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Yukinobu Akamatsu Department of General Medicine, Tottori Municipal Hospital Yuto Haruki Department of Pharmacy, Tsuyama Chuo Hospital Yoshitaka Iwamoto Department of General Medicine, NHO Okayama Medical Center Shuichi Tanaka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shun Fujisato Department of Pharmacy, Okayama Rousai Hospital Soichiro Ako Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background. Candidemia is a life-threatening infection with high mortality, and appropriate management is essential to improve patient outcomes. The Candida Care Bundle aims to standardize hospital management for patients with candidemia and reduce mortality. Methods. This retrospective multicenter cohort study included candidemia cases from 9 hospitals in Japan between 2016 and 2023. Compliance to the Candida Care Bundle was evaluated based on 5 elements: central venous catheter removal within 24 hours, appropriate antifungal therapy, ophthalmologic examination, follow-up blood cultures, and antifungal treatment for ≥2 weeks after clearance. Patients were categorized into high (4–5 items) and low (0–3 items) compliance groups. The primary and secondary outcomes were defined as 30-day survival and the development of endophthalmitis, with propensity score matching used to adjust for potential confounders. Results. Among 230 patients, 160 (69.5%) were classified into the high compliance group, which exhibited significantly lower 30-day mortality than the low compliance group (8.8% vs 57.1%, P < .01). Even after matching, the high compliance group remained independently associated with improved survival (hazard ratio [HR]: 0.15; 95% confidence interval [CI]: .08–.30). C. albicans (HR: 1.95; 95% CI: 1.01–3.52) and central line-associated bloodstream infection (HR: 2.63; 95% CI: 1.35–5.12) were associated with the fatal outcome. Endophthalmitis involved 23.6% of the patients, being associated with C. albicans (odds ratio [OR]: 8.18; 4.46–19.30) and central line-associated bloodstream infection (OR: 2.69; 1.08–6.70). Conclusions. Strict compliance to the Candida Care Bundle significantly improves survival, underscoring its importance in candidemia management. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1759-9954 16 47 2025 Synthesis of sterically unhindered Lewis acidic boron-doped π-conjugated polymers 5035 5039 EN Naoki Takahashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University We report the synthesis of sterically unhindered boron-doped π-conjugated polymers via polymerization of organo-dilithium reagents with boron trichloride. The resulting polymer exhibits Lewis acidity and catalyzes the transesterification of methyl benzoate. This performance is attributed to the electron-accepting ability, and thermally labile Lewis acid–base interactions, facilitating catalytic turnover. No potential conflict of interest relevant to this article was reported.

American Society of Clinical Oncology (ASCO) Acta Medica Okayama 2473-4276 9 2025 Development and Validation of an Ipsilateral Breast Tumor Recurrence Risk Estimation Tool Incorporating Real-World Data and Evidence From Meta-Analyses: A Retrospective Multicenter Cohort Study e2500182 EN Yasuaki Sagara Department of Breast and Thyroid Surgical Oncology, Hakuaikai Sagara Hospital Atsushi Yoshida Department of Breast Surgical Oncology, St Luke's International Hospital Yuri Kimura Department of Breast Surgical Oncology, The Cancer Institute Hospital of JFCR Makoto Ishitobi Department of Breast Surgery, Osaka Habikino Medical Center Yuka Ono Department of Radiation Oncology and Image-Applied Therapy, Kyoto University Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Koji Takada Department of Breast Surgical Oncology, Osaka Metropolitan University Graduate School of Medicine Yuri Ito Department of Medical Statistics, Osaka Medical and Pharmaceutical University Tomo Osako Division of Pathology, The Cancer Institute of Japanese Foundation for Cancer Research Takehiko Sakai Department of Breast Surgical Oncology, The Cancer Institute Hospital of JFCR Purpose Ipsilateral breast tumor recurrence (IBTR) remains a critical concern for patients undergoing breast-conserving surgery (BCS). Reliable risk estimation tools for IBTR risk can support personalized surgical and adjuvant treatment decisions, especially in the era of evolving systemic therapies. We aimed to develop and validate models to estimate IBTR risk. Patients and Methods This multicenter retrospective cohort study included 8,938 women who underwent partial mastectomy for invasive breast cancer between 2008 and 2017. Prediction models were developed using Cox proportional hazards regression and validated via bootstrap resampling. Model performance was assessed using Harrell's C-index, Brier scores, calibration plots, and goodness-of-fit tests. Results During a median follow-up of 9.0 years (IQR, 6.6-10.9), IBTR occurred in 320 patients (3.6%). The initial model, based on variables from Sanghani et al, achieved a Harrell's C-index of 0.74. Incorporating hormonal receptor status, human epidermal growth factor receptor 2 status, radiotherapy, and targeted therapy as predictors reduced the C-index to 0.65, despite their clinical relevance. Importantly, the inclusion of these factors improved calibration, demonstrating better alignment between predicted and observed IBTR probabilities. Although the hazard ratios (HRs) for radiotherapy aligned with the Early Breast Cancer Trialists’ Collaborative Group meta-analyses (MA), those for chemotherapy and endocrine therapy showed slight differences. Therefore, HRs from the MA were used to represent treatment effects in our model. Conclusion We have developed and internally validated a new risk estimation model for IBTR using Cox regression and bootstrap methods. A Web-based risk estimation tool is now available to facilitate individualized risk assessment and treatment planning. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0014-4800 145 2026 Assessing the role of folate syntrophy and folate cross-feeding in the pathobiology of infectious-inflamed milieu caused by Fusobacterium nucleatum 105021 EN Darab Ghadimi Department of Microbiology and Biotechnology, Max Rubner-Institut Sophia Blömer Faculty of Medicine, Christian-Albrechts-University of Kiel Aysel Şahin Kaya Department of Nutrition and Dietetics, Faculty of Health Sciences, Antalya Bilim University Sandra Krüger Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein Christoph Röcken Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein Heiner Schäfer Laboratory of Molecular Gastroenterology & Hepatology, Christian-Albrechts-University & UKSH Campus Kiel 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 Diet and nutrition affect almost every biological process, including multiple chronic diseases, diabetes, and some cancers. However, there are still significant gaps in our understanding of the importance of nutrition and healthy diets in syntrophy with respect to cross-feeding of the microbe-microbe and the microbe-host in the pathobiology of the infectious-inflamed intestinal milieu caused by anaerobic opportunistic bacteria such as Fusobacterium nucleatum (F. nucleatum). We examined the immune outcomes of three-member folate syntrophy and cross-feeding between F. nucleatum bacteria, endogenous folate-producing gut bacteria, and host cells at the host-pathogen interface using a triple co-culture model. T84, THP-1, and Huh7 cells were inoculated with F. nucleatum for 6 h in regular DMEM, DMEM with 9.5 μM folic acid, or with/without a mixture of Bifidobacterium longum subsp. infantis (B. infantis) and Escherichia coli Nissle 1917 (EcN). Cytokine secretion, cometabolite levels (ammonia, indoles), cell viability, and barrier integrity were assessed. F. nucleatum-induced folate depletion was associated with increased IL-1β and IL-6 and decreased IL-22, along with reduced transepithelial electrical resistance (TEER) and cell viability in T84 cells. Folate supplementation mitigated these effects. The mixture of B. infantis and EcN reduced F. nucleatum-induced pro-inflammatory cytokines, increased IL-22, and improved TEER and cell viability. These protective effects were enhanced by the addition of folate. F. nucleatum also elevated ammonia and reduced indoles, effects reversed by B. infantis and EcN. In addition to the intrinsic pathogenicity of harmful bacteria, folate deprivation, microbe–microbe folate syntrophy, and microbe–host folate cross-feeding contribute to the pathobiology of anaerobic opportunistic bacteria and influence the physiological fate of host cells. A combination of B. infantis and EcN modulates the infectious-inflamed interface through a cytoprotective effect and mechanical competitive extrusion of pathogenic F. nucleatum. These results provide potential insights into the mechanisms of early-onset colorectal cancer, and evidently, require future studies using patient-derived organoids and in vivo systems to improve clinical relevance. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1663-9812 16 2025 Regulatory considerations for developing phage therapy medicinal products for the treatment of antimicrobial resistant bacterial infections 1713471 EN Ai Fukaya-Shiba Office of Regulatory Science Coordination, Pharmaceuticals and Medical Devices Agency Akiko Ogata Office of Regulatory Science Coordination, Pharmaceuticals and Medical Devices Agency Ryosuke Kuribayashi Office of Cellular and Tissue-based Products, Pharmaceuticals and Medical Devices Agency Akira Sakurai Office of Cellular and Tissue-based Products, Pharmaceuticals and Medical Devices Agency Kanako Suzuki Office of Regulatory Science Coordination, Pharmaceuticals and Medical Devices Agency Shunsuke Takadama Office of New Drug IV, Pharmaceuticals and Medical Devices Agency Jihei Nishimura Office of New Drug IV, Pharmaceuticals and Medical Devices Agency Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hiroki Ohge Department of Infectious Diseases, Hiroshima University Hospital Takamasa Takeuchi Pathogen Genomics Center, National Institute of Infectious Diseases, Japan Institute for Health Security Hideyuki Tamaki Biomanufacturing Process Research Center, National Institute of Advanced Industrial Science and Technology Tetsuya Matsumoto Department of Infectious Diseases, International University of Health and Welfare Kotaro Kiga Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security Hidetomo Iwano Laboratory of Veterinary Biochemistry, Rakuno Gakuen University School of Veterinary Medicine Recently, there have been growing expectations that treatment of infections with bacteriophages (phages), viruses which specifically infect bacteria, can be used as a treatment option for antimicrobial resistant bacterial infections. In Europe and the United States, in addition to phage therapy as a form of personalized medicine, development of pre-defined phage therapy medicinal products (PTMPs) is progressing, and clinical trials are underway. From October 2024 to July 2025, the Pharmaceuticals and Medical Devices Agency exchanged opinions on trends and points to consider in drug development of PTMPs used for antimicrobial resistant bacterial infections with external experts. Development of PTMPs for regulatory approval requires quality control strategies, establishment of manufacturing methods, non-clinical evaluations, and clinical trial plans based on the characteristics of the phage. In this document, based on the regulatory and development trends in Europe and the United States, the current considerations on quality, non-clinical evaluation, and clinical trial planning including the Cartagena Act in the development of PTMPs in Japan are summarized. The basic concepts presented here are intended to be applied to antimicrobial resistant bacterial infections targeted by PTMPs but can be mostly applicable to bacterial infections in general. We hope that these findings will further accelerate more active development of PTMPs towards timely patient access to innovative products. No potential conflict of interest relevant to this article was reported.

Japan Oil Chemists' Society Acta Medica Okayama 1345-8957 74 11 2025 Bioconversion and Metabolic Fate of the n-1 Polyunsaturated Fatty Acids, 6,9,12,15- Hexadecatetraenoic (C16:4 n-1) and 8,11,14,17- Octadecatetraenoic (C18:4 n-1) Acids, in HepG2 Cells 1023 1032 EN Koki Sugimoto Faculty of Food and Nutritional Sciences, Toyo University Hideto Nishiguchi Faculty of Chemistry, Materials, and Bioengineering, Kansai University Ryota Hosomi Faculty of Chemistry, Materials, and Bioengineering, Kansai University Toshifumi Tanizaki Bizen Chemical Co., Ltd. Tadahiro Tsushima Bizen Chemical Co., Ltd. Naomichi Baba Bizen Chemical Co., Ltd. Yoshihisa Misawa Bizen Chemical Co., Ltd. Ziyi Wang Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuaki Ono Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Murakami Department of Hygiene and Public Health, Kansai Medical University Seiji Kanda Department of Hygiene and Public Health, Kansai Medical University Kenji Fukunaga Faculty of Chemistry, Materials, and Bioengineering, Kansai University Fish oil contains not only major fatty acids with double bonds at the n-3, n-6, n-7, and n-9 positions but also those with a double bond at the n-1 position, such as 6,9,12,15-hexadecatetraenoic acid (C16:4 n-1; HDTA). However, intracellular bioconversion and metabolic fate of n-1 polyunsaturated fatty acids (PUFA) remain unclear. Therefore, in this study, we aimed to assess the intracellular bioconversion and metabolic fate of HDTA and its metabolite, 8,11,14,17- octadecatetraenoic acid (C18:4 n-1; ODTA), using HepG2 cells. Based on the results of cell viability and cytotoxicity assays for HDTA and ODTA, the concentration of each fatty acid supplemented in the experiments was set at 10 μM. HepG2 cell culture with HDTA revealed C20:4 n-1 as a new HDTA metabolite, along with previously reported ODTA. Our findings suggest that the HDTA taken up by HepG2 cells undergoes elongation to form ODTA and C20:4 n-1. Following supplementation with HDTA, ODTA, and 5,8,11,14,17-eicosapentaenoic acid (C20:5 n-3; EPA), fatty acids disappeared from the culture medium within 24 h. Notably, the total relative level of HDTA and its metabolites, including ODTA and C20:4 n-1 in HDTA- and ODTA-supplemented cells were significantly lower than the total relative level of EPA and its metabolites, including 7,10,13,16,19-docosapentaenoic acid (C22:5 n-3), C24:6 n-3, and 4,7,10,13,16,19-docosahexaenoic acid (C22:6 n-3) in the EPA-supplemented cells. Except for a portion that was intracellularly elongated, most HDTA was taken up by HepG2 cells and may undergo rapid fatty acid β-oxidation. However, RNA-sequencing and real-time polymerase chain reaction analysis revealed no significant changes in fatty acid β-oxidation–related gene expression levels in HDTA-supplemented cells. Collectively, these results provide novel insights into the intracellular bioconversion mechanisms and metabolic fate of HDTA and ODTA in HepG2 cells, suggesting that the metabolic fate of n-1 PUFA is distinct from that of common PUFA. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 0099-2240 2025 Efficient resuscitation of early-stage viable but non-culturable cells of Vibrio cholerae using treatment with proteolytic enzymes EN Shin-ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mona Ogasawara Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shiho Niwaki Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Rena Sugihara Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Basilua Andre Muzembo Research Institute of Nursing Care for People and Community, University of Hyogo Daisuke Imamura Research Center for Intestinal Health Science, Okayama University Vibrio cholerae, the etiological agent of cholera, is ubiquitous in environmental brackish waters. Exposure to low water temperatures induces the bacterium to enter a viable but non-culturable (VBNC) state. In this study, a stepwise decrease in water temperature to 4°C was found to delay the transition to the non-culturable state compared to an abrupt temperature drop, suggesting that V. cholerae cells partially adapt to low temperatures. V. cholerae VBNC cells maintained at 4°C gradually lost their ability to revert to a culturable state. However, VBNC cells in the early stage of dormancy were efficiently resuscitated following treatment with proteolytic enzymes, including proteinase K. The abundance of culturable V. cholerae cells in brackish estuarine waters was quantified using the most probable number (MPN)–quantitative polymerase chain reaction (qPCR) method. Although culturable cells were undetectable in samples treated with bovine serum albumin, they were estimated at 93 and 1,500 MPN/mL in two water samples collected on different days and pre-incubated with proteinase K. Similarly, the abundance of Vibrio species increased markedly following treatment with this enzyme. Additionally, cells of Vibrio species were enumerated by the plating method using CHROMagar Vibrio plates. Consistent with the results of the MPN–qPCR method, treatment with proteinase K resulted in over a 100-fold increase in colony formation. Collectively, these findings suggest that treatment with proteinase K is effective for resuscitating and quantifying V. cholerae VBNC cells in environmental water samples. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Single cell spatial transcriptomics links Wnt signaling disruption to extracellular matrix development in a cleft palate model 29639 EN Jeremie Oliver Piña Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Resmi Raju Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Evan Stipano Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Aye Chan Myo Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Ziyi Wang Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Department of Molecular Biology and Biochemistry, Okayama University Mitsuaki Ono Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Department of Molecular Biology and Biochemistry, Okayama University Parna Chattaraj Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Masae Furukawa Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Rena N. D’Souza Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Despite advances in understanding the morphological disruptions that lead to defects in palate formation, the precise perturbations within the signaling microenvironment of palatal clefts remain poorly understood. To explore in greater depth the genomic basis of palatal clefts, we designed and implemented the first single cell spatial RNA-sequencing study in a cleft palate model, utilizing the Pax9−/− murine model at multiple developmental timepoints, which exhibits a consistent cleft palate defect. Visium HD, an emerging platform for true single-cell resolution spatially resolved transcriptomics, was employed using custom bins of 2 × 2 μm spatial gene expression data. Validation of spatial gene expression was then validated using custom designed Xenium In Situ mRNA spatial profiling and RNAscope Multiplex assays. Functional enrichment analysis revealed a palate cell-specific perturbation in Wnt signaling effector function in tandem with disrupted expression of extracellular matrix genes in developing mesenchyme. As a key step toward laying the framework for identifying key molecular targets these data can be used for translational studies aimed at developing effective therapies for human palatal clefts. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1341-321X 31 12 2025 Whole-genome sequencing and in vitro characterization of a disseminated ST398 Staphylococcus aureus infection: A case report 102845 EN Yosuke Sazumi Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinnosuke Fukushima Department of Bacteriology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Atsushi Kato Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuhito Suyama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Oguni Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Shoko Kutsuno Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Junzo Hisatsune Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Motoyuki Sugai Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security Shuma Tsuji Department of Bacteriology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Staphylococcus aureus potentially causes systemic infections such as disseminated abscesses and bloodstream infections, leading to high mortality rates. We herein describe a case of disseminated muscle abscesses caused by sequence type (ST) 398 methicillin-sensitive S. aureus (MSSA), along with in vitro investigation results for potential pathogenic factors. A 67-year-old healthy woman was admitted to our hospital with complaints of systemic body pain. Blood cultures identified MSSA and contrast-enhanced computed tomography revealed multiple muscle abscesses extending from her neck to her soles. She received antibiotic treatment with intravenous cephazolin and underwent repeated surgical drainage, and was finally discharged. Notably, the MSSA strain exclusively affected her muscle tissues, prompting us to perform genetic analysis to uncover the underlying reason. Short-read genome analysis revealed the isolate to be ST398, harboring chp and scn genes known for immune evasion from human immunity. However, no other known pathogenic factors were identified despite rigorous assays for biofilm formation, surface and cell wall proteins, protease production, and hyaluronidase activity. ST398 S. aureus is commonly isolated from livestock, and her prior experience of being flooded could be related to the disease onset. The present case underscores the possibility of severe ST398 MSSA infections in humans, even in the absence of direct animal exposure. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1341-321X 31 12 2025 Clinical and molecular characteristics of urinary catheter-associated Pseudomonas aeruginosa prostatic infection: A case series of four postoperative nosocomial infections 102853 EN Shinnosuke Fukushima Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Sano Laboratory of Veterinary Public Health, School of Veterinary Medicine and Animal Sciences, Kitasato University Takashige Kashimoto Laboratory of Veterinary Public Health, School of Veterinary Medicine and Animal Sciences, Kitasato University Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Pseudomonas aeruginosa is a causative pathogen of nosocomial catheter-associated urinary tract infections (CAUTI), but prostate involvement, including prostatitis and prostatic abscess, is rare. The clinical characteristics of P. aeruginosa-associated CAUTI with prostatic lesions, as well as the contribution of genetic backgrounds remain unclear. We describe four cases of urinary catheter-associated prostatic infection caused by P. aeruginosa following postoperative catheterization. All patients developed fever within 10 days after surgery, and three of the four patients developed bacteremia. Three patients were diagnosed with prostatic abscess by contrast-enhanced computed tomography or magnetic resonance imaging, while one case presented with prostatitis without abscess formation. Prostate-specific antigen levels were elevated over 20 ng/mL in all three measured cases. All patients were treated successfully with prolonged antibiotic therapy (28–39 days) without surgical drainage. Notably, all three abscess cases were successfully managed with fluoroquinolone-based combination therapy, highlighting its potential role in the management of prostatic abscesses. Three of four isolates were submitted for molecular investigations. All isolates harbored exoT and exoY, whereas exoU was absent. Biofilm-associated genes were detected in two cases, but not in the remaining case. Our findings suggested that P. aeruginosa strains carrying T3SS genes (exoT and exoY) potentially develop prostatic infections, independent of biofilm-associated genes. Host and iatrogenic factors, such as catheter manipulation, may play more critical roles in the development of prostatic pathology than strain-specific determinants. Assessment of prostate-specific antigen levels and early imaging may facilitate appropriate diagnosis and effective management when P. aeruginosa is detected as a cause of CAUTI. No potential conflict of interest relevant to this article was reported.

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

MDPI AG Acta Medica Okayama 2313-433X 12 1 2025 FluoNeRF: Fluorescent Novel-View Synthesis Under Novel Light Source Colors and Spectra 16 EN Lin Shi Department of Artificial Intelligence, Kyushu Institute of Technology Kengo Matsufuji Department of Artificial Intelligence, Kyushu Institute of Technology Michitaka Yoshida Department of Computer Science, Okayama University Ryo Kawahara Graduate School of Informatics, Kyoto University Takahiro Okabe Department of Computer Science, Okayama University Synthesizing photo-realistic images of a scene from arbitrary viewpoints and under arbitrary lighting environments is one of the important research topics in computer vision and graphics. In this paper, we propose a method for synthesizing photo-realistic images of a scene with fluorescent objects from novel viewpoints and under novel lighting colors and spectra. In general, fluorescent materials absorb light with certain wavelengths and then emit light with longer wavelengths than the absorbed ones, in contrast to reflective materials, which preserve wavelengths of light. Therefore, we cannot reproduce the colors of fluorescent objects under arbitrary lighting colors by combining conventional view synthesis techniques with the white balance adjustment of the RGB channels. Accordingly, we extend the novel-view synthesis based on the neural radiance fields by incorporating the superposition principle of light; our proposed method captures a sparse set of images of a scene from varying viewpoints and under varying lighting colors or spectra with active lighting systems such as a color display or a multi-spectral light stage and then synthesizes photo-realistic images of the scene without explicitly modeling its geometric and photometric models. We conducted a number of experiments using real images captured with an LCD and confirmed that our method works better than the existing methods. Moreover, we showed that the extension of our method using more than three primary colors with a light stage enables us to reproduce the colors of fluorescent objects under common light sources. 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 Perioperative Multidisciplinary Intervention Led to Complete Minimally Invasive Transthoracic Esophagectomy for a Patient With Severe Lung Dysfunction: A Case Report e97931 EN Makoto Matsumoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kento Kawasaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomoyoshi Kunitomo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Risk factors for postoperative pneumonia after esophagectomy include smoking, severe lung dysfunction, and sarcopenia. Heavy smokers often have chronic obstructive pulmonary disease (COPD), which is associated with poor physical activity and low muscle strength. Sarcopenia is also associated with decreased physical function and malnutrition. These factors lead to a close relationship between COPD and sarcopenia. This report describes the case of a 74-year-old man who presented with dysphagia and was diagnosed with advanced esophageal cancer with lymph node metastasis. Preoperative respiratory function testing showed a forced expiratory volume in one second (FEV1) of 0.76 L because of his past smoking and COPD. Multidisciplinary intervention was started, along with neoadjuvant chemotherapy. Preoperative management improved his physical function. Robot-assisted thoracoscopic subtotal esophagectomy with the patient in the prone position was performed with curative resection and no severe postoperative complications. The perioperative multidisciplinary intervention improved physical functions and enabled safe robot-assisted thoracoscopic esophagectomy for the patient with severe lung dysfunction in the prone position. This case highlights that not only respiratory status but also physical parameters should be taken into account when considering whether a patient can tolerate surgery safely. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1758-5902 18 1 2025 A Procedural Transhiatal Approach for the Thoracic Para‐Aortic Lymph Node: A Case Report e70066 EN Masashi Hashimoto 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 Yasushige Takeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hijiri Matsumoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kento Kawasaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyoshi Kunitomo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The thoracic posterior para-aortic lymph node (TPAN) is classified as an extra-regional lymph node in esophageal cancer, with metastasis indicating poor prognosis. However, some cases with suspected TPAN metastasis may benefit from esophagectomy with lymph node dissection, including TPAN. This report presents the case of a 58-year-old man with upper thoracic esophageal squamous cell carcinoma and suspected simultaneous TPAN metastasis who underwent neoadjuvant chemotherapy followed by thoracoscopic subtotal esophagectomy and procedural transhiatal TPAN dissection. This transhiatal approach provided direct access to the lymph node without additional thoracic incisions, ensuring safe resection in coordination with the assistant and following anatomical landmarks systematically. Pathological examination showed a false-positive TPAN finding, though the patient later developed distant recurrence. Compared with conventional approaches, this transhiatal technique allows for procedural and reproducible lymphadenectomy while minimizing respiratory burden. This case highlights the feasibility of a transhiatal approach for TPAN dissection. 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 44 2025 Structural insights into the divergent evolution of a photosystem I supercomplex in Euglena gracilis eaea6241 EN Koji Kato Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiki Nakajima Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Runa Sakamoto Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Minoru Kumazawa Institute of Low Temperature Science, Hokkaido University Kentaro Ifuku Graduate School of Agriculture, Kyoto University Takahiro Ishikawa Institute of Agricultural and Life Sciences, Academic Assembly, Shimane University Jian-Ren Shen Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Atsushi Takabayashi Institute of Low Temperature Science, Hokkaido University Ryo Nagao Faculty of Agriculture, Shizuoka University Photosystem I (PSI) forms supercomplexes with light-harvesting complexes (LHCs) to perform oxygenic photosynthesis. Here, we report a 2.82-angstrom cryo–electron microscopy structure of the PSI-LHCI supercomplex from Euglena gracilis, a eukaryotic alga with secondary green alga-derived plastids. The structure reveals a PSI monomer core with eight subunits and 13 asymmetrically arranged LHCI proteins. Euglena LHCIs bind diadinoxanthin, which is one of the carotenoids typically associated with red-lineage LHCs and is not present in the canonical LHCI belt found in green-lineage PSI-LHCI structures. Phylogenetic analysis shows that the Euglena LHCIs originated from LHCII-related clades rather than from the green-lineage LHCI group and that the nuclear-encoded PSI subunit PsaD likely originated from cyanobacteria via horizontal gene transfer. These observations indicate a mosaic origin of the Euglena PSI-LHCI. Our findings uncover a noncanonical light-harvesting architecture and highlight the structural and evolutionary plasticity of photosynthetic systems, illustrating how endosymbiotic acquisition and lineage-specific adaptation shape divergent light-harvesting strategies. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 0143-005X 80 2 2025 Exposure-induced mediator–outcome confounders in causal mediation: implications and visualisation 129 130 EN Etsuji Suzuki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Shinozaki Interfaculty Initiative in Information Studies, the University of Tokyo Eiji Yamamoto Okayama University of Science No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2673-7086 5 4 2025 An Integrated QGIS-Based Evacuation Route Optimization Approach for Disaster Preparedness Against Urban Flood in Japan 74 EN Wenliang Pan Graduate School of Environmental and Life Science, Okayama University Shijun Pan Graduate School of Environmental and Life Science, Okayama University Junko Kaneto Graduate School of Environmental and Life Science, Okayama University Keisuke Yoshida Graduate School of Environmental and Life Science, Okayama University Satoshi Nishiyama Graduate School of Environmental and Life Science, Okayama University Urban inland flooding has become a serious problem in many cities because heavy rain often exceeds the capacity of drainage systems. In Japan, GIS-based evacuation maps are commonly used to support disaster preparedness, but they still have several limitations. In particular, they do not avoid flooded road segments and cannot generate multiple evacuation options at the same time. This study proposes an improved evacuation route method using the free and open-source software QGIS. The method combines flood-depth data with road network processing to remove roads where the predicted water depth is higher than 0.5 m. It also provides several evacuation paths to different shelters at the same time. A case study in Kurashiki City, Okayama Prefecture, demonstrates that about 1.37% of the road network becomes unusable during an inland-flood scenario. Several existing evacuation routes also pass through hazardous areas, but the QGIS-based method avoids these areas in most cases. Since the workflow uses only built-in QGIS functions and does not require programming or plug-ins, it is easy to reproduce and apply in other regions. This study offers a practical and low-cost method to support inland-flood evacuation planning for local governments. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2694-2445 5 6 2025 Electronic Structure of the S1 State Manganese Cluster in Photosystem II Investigated Using Q-Band Selective Hole-Burning 660 671 EN Shinya Kosaki Department of Physics, Graduate School of Science, Nagoya University Naohiko Nakamura Department of Physics, Graduate School of Science, Nagoya University Yoshiki Nakajima Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Jian-Ren Shen Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyuki Mino Department of Physics, Graduate School of Science, Nagoya University The electronic structure of the S1 state of photosystem II (PSII) was investigated using selective hole burning of Q-band pulsed electron paramagnetic resonance. The free induction decay and spin–echo signals of the tyrosine radical YD• in the plant PSII oscillated because of the magnetic dipole–dipole interaction with the S1 state Mn cluster. The initial period was 410 ns (2.44 MHz) and was assigned to the S = 1 spin state. Based on the oscillation analysis, both Mn1 and Mn4 and both Mn2 and Mn3 were assigned as Mn(III) and Mn(IV), respectively, which is consistent with the quantum chemical calculations. The 410 ns period was accounted for in the simplified model using the isotropic spin density distribution ratio [1.6:–1.1:–1.1:1.6] for Mn1–4 ions. This oscillation was identical with that observed in the presence of methanol. The oscillation decreased in PsbP/Q- and PsbO/P/Q-depleted PSII. In Thermosynechococcus vulcanus, two periods, 390 ns (2.56 MHz) and 630 ns (1.59 MHz), were detected, indicating that the cyanobacterial S1 state includes two isomers, S = 1 and S ≥ 2 spins. The S ≥ 2 spin was not detected in PsbO/U/V-depleted PSII without polyethylene glycol. The S ≥ 2 state was consistent with the reported quantum chemical calculation using S = 3. A simplified model accounted for the S = 1 state as the spin density distribution [1.8:–1.3:–1.3:1.8] and for the S ≥ 2 state as the isotropic spin density distribution [−0.5:0.5:0.5:0.5] for Mn1–4 ions. In combination with quantum chemical calculations, the most probable protonated structure is W1 = H2O, W2 = H2O, O4 = O2–, and O5 = O2– for the S1 state. These results demonstrate that the selective hole burning method is a powerful tool to complement X-ray studies to determine the valence and protonation structure of manganese clusters, not only in the S1 state but also in higher S-states and general metal clusters, which would provide important insights into the water oxidation mechanism. No potential conflict of interest relevant to this article was reported.

Spandidos Publications Acta Medica Okayama 2049-9450 23 5 2025 Prolonged exposure to axitinib alters the molecular profile of Caki‑2 renal cell carcinoma cells 101 EN Yuko Nakayama Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University Aya Ino Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University Kazuhiro Yamamoto Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohji Takara Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University Axitinib, an oral second‑generation multitargeted tyrosine kinase inhibitor, is used as a second‑line treatment for metastatic renal cell carcinoma (RCC). However, patients often develop resistance after initial responsiveness, necessitating the elucidation of the underlying resistance mechanisms. Therefore, the present study aimed to investigate the mechanisms underlying axitinib resistance using the Caki‑2 human papillary RCC model cells. Cells tolerating 0.1 µM axitinib were designated as Caki/AX cells. Cell viability was assessed using the water‑soluble tetrazolium salt assay. Notably, the 50% inhibitory concentration (IC50) values of axitinib and sunitinib were significantly higher in Caki/AX cells than those in Caki‑2 cells, indicating 2.83‑ and 1.2‑fold resistance, respectively. By contrast, the IC50 values of sorafenib and erlotinib were decreased in Caki/AX cells. Moreover, Caki/AX cells showed resistance to everolimus, temsirolimus and rapamycin, and decreased sensitivity to vinblastine, vincristine, paclitaxel, doxorubicin and SN‑38 compared with Caki‑2 cells. Notably, etoposide, 5‑fluorouracil, cisplatin and carboplatin sensitivities were comparable in both cell types. Reverse transcription‑quantitative polymerase chain reaction (PCR) analysis revealed that the mRNA levels of the ATP‑binding cassette subfamily B member 1 and subfamily G member 2 were significantly higher in Caki/AX cells than those in Caki‑2 cells. A PCR array related to vascular endothelial growth factor signalling showed that the mRNA levels of FIGF (also known as vascular endothelial growth factor D) and sphingosine kinase 1 were upregulated, whereas those of Rac family small GTPase 2 were downregulated in Caki/AX cells. Overall, these findings suggested that the upregulation of the ATP‑binding cassette subfamily B member 1, FIGF and sphingosine kinase 1 mRNA levels, and downregulation of the Rac family small GTPase 2 mRNA levels may contribute to acquired resistance in Caki/AX cells. No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 2366-1070 13 4 2025 Asian Subgroup Analysis of Patients in the Phase 2 DeLLphi-301 Study of Tarlatamab for Previously Treated Small Cell Lung Cancer 1041 1054 EN Myung-Ju Ahn Hematology-Oncology Department, Samsung Medical Center (SMC), Sungkyunkwan University School of Medicine Byoung Chul Cho Medical Oncology Department-501, ABMRC, Yonsei University Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Hiroki Izumi Thoracic Oncology, National Cancer Center Hospital East Jong-Seok Lee Hematology/Oncology, Seoul National University Bundang Hospital Ji-Youn Han Center for Lung Cancer, National Cancer Center-Graduate School of Cancer Science and Policy Chi-Lu Chiang Department of Chest Medicine, Taipei Veterans General Hospital Shuang Huang Amgen Inc. Ali Hamidi Amgen Inc. Sujoy Mukherjee Amgen Inc. Krista Lin Xu Amgen Asia Pacific Pte. Ltd. Hiraoki Akamatsu Internal Medicine III, Wakayama Medical University Introduction: Tarlatamab is a bispecific T-cell engager (BiTE®) immunotherapy that binds delta-like ligand 3 on the surface of small cell lung cancer (SCLC) cells and CD3 on T cells, facilitating T cell-mediated cancer cell lysis. In the primary analysis of the phase 2 DeLLphi-301 study (NCT05060016), tarlatamab showed a favourable benefit-to-risk profile with durable objective responses and promising survival outcomes in patients with previously treated SCLC. Here, phase 2 data for the Asia region subgroup are presented. Methods: Patients with previously treated, advanced SCLC received 10 mg tarlatamab every 2 weeks. The primary endpoint was objective response rate (ORR) by blinded independent central review (RECIST version 1.1). Key secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety. The present analysis includes patients enrolled at sites in Asia. Results: A total of 43 patients were enrolled at sites in Asia. ORR was 46.3% (95% confidence interval [CI], 30.7–62.6) and median DOR was 7.2 months (95% CI 3.9 to not estimable). The median follow-up was 16.6 months for PFS and 21.2 months for OS. Median PFS was 5.4 months (95% CI 3.0–8.1) and median OS was 19.0 months (95% CI 11.4 to not estimable). The most common treatment-emergent adverse event (AE) was cytokine release syndrome (48.8%), and all such events were grade 1 or 2. There were no discontinuations due to treatment-related AEs. Conclusions: Tarlatamab demonstrated durable responses and promising survival outcomes with a manageable safety profile in this post hoc analysis of patients from Asia with previously treated SCLC. Trial Registration: ClinicalTrials.gov, NCT05060016. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0753-3322 193 2025 Deciphering the structural impact of norepinephrine analog radiopharmaceuticals on organic cation transporter affinity 118724 EN Saskia Mühlig Department of Nuclear Medicine and Comprehensive Heart Failure Center, University Hospital Würzburg Xinyu Chen Nuclear Medicine, Faculty of Medicine, University of Augsburg Anna Tutov Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, University of Würzburg Naoko Nose Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Constantin Lapa Nuclear Medicine, Faculty of Medicine, University of Augsburg Rudolf A. Werner Department of Nuclear Medicine, LMU Hospital, Ludwig-Maximilians-University of Munich Michael Decker Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, University of Würzburg Takahiro Higuchi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose: Previous studies have investigated the kinetics and affinities of norepinephrine transporter (NET)-targeting radiotracers, including [123I]MIBG, but the role of organic cation transporters (OCTs) remains unclear. This study aimed to evaluate how the structural design of selective NET-targeting tracers affects OCT-mediated non-specific uptake, identifying factors influencing both NET and OCT affinity. Methods: Cellular uptake assays were conducted using SK-N-SH cells expressing human NET, and human OCT1-, OCT2-, and OCT3-expressing cells with [3H]norepinephrine, [3H]MPP+, and [131I]MIBG. Competitive uptake assays used non-radioactive reference compounds for several NET-targeting radiopharmaceuticals (MIBG, HED, EPI, PHEN, LMI1195, and PHPG), along with a new PET radiotracer [18F]AF78, and its two analogs with meta-iodide [18F]AF78(I) or hydroxyl group [18F]AF78(OH). Dynamic PET imaging in non-human primates assessed the in vivo uptake of [18F]AF78 after NET inhibition with desipramine. Results: Monoamine-based tracers (EPI, PHEN, HED) exhibited high NET selectivity with minimal OCTs interaction, while guanidine-containing tracers (e.g., MIBG, LMI1195) displayed substantial OCTs affinity. Lower lipophilicity in guanidine-containing compounds, influenced by substitutions on the benzene ring (e.g., PHPG, AF78), correlated with weaker OCT interactions. PET imaging confirmed that cardiac uptake of [18F]AF78 is sensitive to desipramine pretreatment (***P < 0.0005), indicating its NET-specificity, while persistent hepatic retention suggests an OCT-mediated transport mechanism. Conclusion: This study highlights the critical influence of the compounds’ chemical structure on NET and OCT affinities. Structural modifications that reduce OCT-mediated uptake while maintaining high NET affinity could improve the specificity and theranostic potential of NET-targeting ligands. These findings provide insights for designing next-generation radiotracers with enhanced selectivity and clinical utility. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0919-8172 2025 Daytime Bladder Control Status in Toddlerhood Is Associated With Subsequent Bedwetting in Preschool Years: A Nationwide Cohort Study of Over 30 000 Japanese Children EN Takatoshi Moriwake Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naomi Matsumoto Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Tominaga Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kensuke Uraguchi Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoko Kobayashi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ichiro Tsuboi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kasumi Yoshinaga Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoaki Yamanoi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsushi Kawada Department of Urology Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Okayama Japan Takuya Sadahira Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Katayama 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 Shingo Nishimura Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kensuke Bekku Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohei Edamura Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soshi Takao Department of Epidemiology, 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 Motoo Araki Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: Nocturnal enuresis is common in early childhood. While daytime bladder control typically precedes nighttime continence, the temporal relationship between early daytime bladder control and subsequent bedwetting remains unclear. We investigated whether daytime bladder control status at age 2.5 years—as indicated by diaper use—is associated with bedwetting at age 4.5 years in a Japanese nationwide cohort. Methods: We analyzed data from the Japanese Longitudinal Survey of Newborns in the 21st Century (2010 cohort). Daytime bladder control was assessed at age 2.5 years through caregiver-reported diaper use, and bedwetting frequency at age 4.5 years through parental questionnaires. Modified Poisson regression estimated risk ratios (RRs), adjusting for birth-related factors, socioeconomic status, daycare attendance, and developmental milestones. Results: Among 32 168 children, 26 651 (82.8%) still used diapers at 2.5 years. Bedwetting prevalence at 4.5 years was 42.2%: 34.5% in children who achieved daytime bladder control at 2.5 years versus 43.9% in those still using diapers. After multivariable adjustment, incomplete daytime bladder control at 2.5 years was associated with higher bedwetting risk (adjusted RR 1.25; 95% CI, 1.20–1.31). Multinomial regression revealed dose–response relationships: odds ratios 1.41 (95% CI, 1.30–1.52) for “sometimes” and 1.58 (95% CI, 1.42–1.77) for “often” bedwetting. Conclusions: Daytime bladder control status at 2.5 years was associated with a 25% increased bedwetting risk at 4.5 years. This association likely reflects individual differences in bladder control maturation rather than causal effects. While daytime bladder control may serve as a developmental marker, its validity as an intervention target remains unestablished. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0732-8893 113 4 2025 Time to positivity for differentiating blood culture contamination: A 20-hour cutoff for major contaminants 117030 EN Yohei Manabe Department of Pharmacy, Okayama University Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Kenta Nakamoto Department of Infectious Diseases, Okayama University Hospital Kohei Oguni Department of Infectious Diseases, Okayama University Hospital Hidemasa Akazawa Department of Infectious Diseases, Okayama University Hospital Yasushi Fujita Department of Nursing, Okayama University Hospital Takashi Kiguchi Department of Nursing, Okayama University Hospital Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Background: Blood culture remains the gold standard for diagnosing bacteremia; however, contamination inevitably occurs in 2-3% of cases, requiring differentiation between true bacteremia and contamination. Although time to positivity (TTP) aids in this clinical decision, with detection after 24 hours generally indicating contamination, technological advances in blood culture systems may have shortened this threshold interval. Methods: This study retrospectively analyzed blood culture data in our hospital from April 2023 to January 2025 to determine the optimal TTP cutoff. Patients with positive blood cultures for major contaminating bacteria were included. Cases were classified as true bacteremia or contamination based on a comprehensive chart review conducted by the antimicrobial stewardship audit, and TTP was compared between the groups. Sensitivity, specificity, and Youden index at various TTP cutoffs were utilized to determine the optimal threshold using the receiver operating characteristic curve analysis. Results: Seventy-one patients were enrolled, with 34 cases classified as true bacteremia and 37 as contamination. Identified bacteria included coagulase-negative staphylococci (70.4%), viridans group streptococci (18.3%), and others (11.3%). The median TTP was significantly shorter in the true bacteremia group compared with the contamination group (18.6 vs.25.8 hours, p < 0.001). In the contamination group, 43.2% of the cases demonstrated positive growth within 24 hours. Based on sensitivity, specificity, and Youden index, the optimal threshold was estimated to be 20 hours. A subgroup analysis of the CNS-only cohort yielded concordant results. Conclusion: This study suggests that a 20-hour TTP threshold could help effectively differentiate true bacteremia from contamination in current clinical settings. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 13 12 2025 Experience and Insight Into Genetic Diagnosis of Infective Aortic Aneurysm e71586 EN Shinnosuke Fukushima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takumi Fujimori Microbiology Division, Clinical Laboratory, Okayama University Hospital Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Culture-negative infected aneurysms possibly occur in various clinical situations, including prior antibiotic exposure. Accurate microbial identification is crucial for an optimal antimicrobial strategy. 16S ribosomal RNA gene sequence analysis would provide a useful tool for precise bacterial identification. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 13 12 2025 Mycobacterium intracellulare-Induced Flexor Tenosynovitisof the Forearm e71698 EN Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Kenta Nakamoto Department of Infectious Diseases, Okayama University Hospital Kohei Oguni Department of Infectious Diseases, Okayama University Hospital We herein document a clinically challenging case of Mycobacterium intracellulare tenosynovitis in an immunocompromised patient with rheumatoid arthritis. Diagnosing nontuberculous mycobacterial tenosynovitis is often challenging because it often mimics rheumatoid arthritis flares. Combination antimycobacterial therapy combined with surgical intervention is essential for the treatment of this refractory condition. No potential conflict of interest relevant to this article was reported.

American Society of Tropical Medicine and Hygiene Acta Medica Okayama 0002-9637 113 5 2025 Scapular Tuberculosis 942 943 EN Kenta Nakamoto Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Kohei Oguni Department of Infectious Diseases, Okayama University Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

European Respiratory Society (ERS) Acta Medica Okayama 2312-0541 11 6 2025 Global trends in idiopathic pulmonary fibrosis mortality rates during 2001–2022 00362-2025 EN Ko Harada Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai Yoshito Nishimura Division of Hematology/Oncology, Mayo Clinic Quynh Thi Vu Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Maki Yamamoto Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and ultimately fatal lung disease. Updated global mortality data, especially from underexplored countries, are limited. This study aimed to understand the current global trends in IPF-associated mortality rates. Methods This observational study used the World Health Organization Mortality Database to analyse data stratified by sex, age and geographic region, encompassing 64 countries between 2001 and 2022. IPF was defined according to the International Code for Diseases-10 code J84.1. Crude and age-standardised mortality rates per 100 000 individuals were calculated to estimate long-term mortality trends. Mortality rates were calculated by dividing IPF-associated deaths by the corresponding population, with age-specific rates determined for each 5-year age group. Trends in the 2001–2022 period were analysed using a locally weighted regression model, and the average annual percentage change in mortality rates between 2010 and 2022 was estimated using joinpoint regression analysis. Results Overall, 874 998 deaths associated with IPF were analysed. The LOESS-smoothed crude mortality rate increased from 2.10 (95% confidence interval (CI) 1.77–2.43) per 100 000 in 2001 to 3.14 (95% CI 2.71–3.57) per 100 000 by 2022. The LOESS-smoothed age-standardised mortality rates increased overall, peaking at 1.59 (95% CI 1.51–1.67) per 100 000 in 2018 and declining slightly to 1.57 (95% CI 1.35–1.79) per 100 000 in 2022. Mortality was higher among males than females; furthermore, 87.5% of deaths occurred in individuals aged ≥65 years. Mortality rates were highest among the American population, with a notable increase in Latin American countries. Conclusion IPF-associated mortality rates have increased globally, particularly in males. Significant geographical, age and sex disparities were observed, emphasising the need for targeted public health measures and improved disease management. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 13 10 2025 Recurrent Septic Shock in Immunosuppressed Patients e71249 EN Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Koji Fujita Department of General Medicine and Infectious Diseases, Tsuyama Chuo Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Cytomegalovirus gastroenteritis presents with diarrhea and abdominal pain in immunosuppressed patients, and histopathological examination is essential by endoscopy. This case illustrates that cytomegalovirus enteritis may develop insidiously and possibly invoke shock in immunocompromised patients, warranting its inclusion in the differential diagnosis of recurrent septic shock. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0300-8126 2025 Hospital-acquired pneumonia caused by multidrug-resistant Streptococcus pneumoniae serotype 15A EN Hidemasa Akazawa Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Kenta Nakamoto Department of Infectious Diseases, Okayama University Hospital Kohei Oguni Department of Infectious Diseases, Okayama University Hospital Madoka Shimbe Department of Infectious Diseases, Okayama University Hospital Bin Chang Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security Yukihiro Akeda Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background Streptococcus pneumoniae remains a common cause of community-acquired pneumonia but is an infrequent pathogen in hospital-acquired pneumonia (HAP). Non-vaccine serotypes of multidrug-resistant (MDR) S. pneumoniae strains have been emerging globally, posing an increased risk of nosocomial infection. Case A 71 year-old man developed pneumonia on postoperative day 4 following spinal fusion surgery. Despite initial treatment with ampicillin/sulbactam, his condition deteriorated, requiring ICU admission and mechanical ventilation. Microbiological testing confirmed S. pneumoniae as a causative pathogen, and ceftriaxone was empirically administered based on the local antibiogram. However, antimicrobial susceptibility testing revealed resistant profiles to penicillin (minimum inhibitory concentration [MIC], 8 µg/mL), ceftriaxone (MIC, 16 µg/mL), meropenem (MIC, 1 µg/mL), macrolides, and clindamycin, while demonstrating susceptibility to levofloxacin and vancomycin. The therapeutic regimen was subsequently adjusted to levofloxacin, resulting in clinical improvement. The isolate was later identified as serotype 15A, sequence type 63 (ST63). Conclusion This case highlights that MDR S. pneumoniae can cause early-onset HAP and may not be covered by standard empiric therapies, emphasizing the need for careful evaluation of treatment response. Continued surveillance of infections caused by vaccine-escape clones like MDR serotype 15A is essential, given their increasing clinical relevance. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0301-486X 190 6 2025 Prognostic Value of Serum (1→3)-β-D-Glucan Levels in Patients with Candidemia Stratified by Compliance with Candida Bundle: A Multicenter Retrospective Cohort Study (2016–2023) 90 EN Hidemasa Akazawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Toshie Higuchi Department of General Internal Medicine, Okayama Red Cross Hospital Tomoko Miyoshi Center for Medical Education and Internationalization, Kyoto University Graduate School of Medicine Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Yukinobu Akamatsu Department of General Medicine, Tottori Municipal Hospital Yuto Haruki Department of Pharmacy, Tsuyama Chuo Hospital Yoshitaka Iwamoto Department of General Medicine, NHO Okayama Medical Center Shuichi Tanaka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shun Fujisato Department of Pharmacy, Okayama Rousai Hospital Soichiro Ako Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background Candidemia is a severe systemic infection with a high mortality risk. While β-D-glucan (BDG) serves as a diagnostic biomarker, its prognostic value in candidemia, particularly in association with Candida bundle compliance, remains unclear. Methods In this retrospective multicenter cohort study, we evaluated 96 patients with candidemia across nine Japanese hospitals between 2016 and 2023. Candida bundle compliance was assessed using five key components: central venous catheter removal within 24 h of diagnosis, appropriate initial antifungal therapy, ophthalmologic examination, follow-up blood cultures until clearance, and antifungal therapy for at least two weeks post-clearance. Analyses stratified patients by serum BDG status (positive/negative) and compliance with the Candida bundle (high: 4–5 points; low: 0–3 points). The primary outcome was 30-day mortality, and the secondary outcome was defined as endophthalmitis incidence. Results Of 96 eligible patients with candidemia, 70 (72.9%) were BDG-positive and 26 (27.1%) were BDG-negative. The overall 30-day mortality was 17.7%. Among BDG-positive patients, 15 (21.4%) died, while 2 (7.7%) died in BDG-negative cohorts (p = 0.09). Serum BDG positivity demonstrated a statistically significant association with decreased survival rates in the low bundle adherence group (p = 0.02), whereas this correlation was not observed among patients in the high-compliance cohort (p = 0.66). Endophthalmitis occurred in 25.0% of patients, without significant correlation to serum BDG status. C. albicans was associated with a significantly higher incidence of endophthalmitis compared with non-albicans species (45.7% vs. 8.9%). Conclusions Serum BDG positivity potentially correlates with worse survival in candidemia, particularly in patients with low bundle compliance. This emphasizes the importance of adherence to standardized Candida management protocols for optimizing patient outcomes. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2772-7076 16 2025 Should Japanese athletes undergo booster vaccination for pertussis? 100718 EN Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Pertussis, a highly contagious respiratory infection caused by Bordetella pertussis, has demonstrated a global resurgence in the post–COVID-19 era, with the emergence of macrolide-resistant strains. In Japan, the routine immunization schedule for pertussis remains limited compared with international standards, leaving young populations under-immunized and at elevated risk of infection. Despite international recommendations for booster vaccinations during adolescence, Japan currently provides only a four-dose primary series during infancy, without subsequent boosters. This immunization gap possibly increases the vulnerability of Japanese athletes to pertussis. Persistent cough can significantly impair athletic performance for weeks to months, posing substantial challenges to professional sports teams. To protect athletes’ health and performance capacity and prevent team-wide outbreaks, it is imperative to consider pertussis booster immunizations in Japan, especially for elite athletes. However, DTaP (diphtheria, tetanus, and acellular pertussis) (TRIBIKⓇ) is the only available vaccine in Japan, which contains higher antigen concentrations than the internationally used Tdap (tetanus, diphtheria, pertussis) vaccines (ADACEL™ and BOOSTRIXⓇ): the antigen contents of pertussis toxin, filamentous hemagglutinin, and diphtheria toxin in TRIBIKⓇ, ADACEL™, and BOOSTRIXⓇ are 23.5 µg/23.5 µg/≤15 µg, 2.5 µg/5 µg/2 µg, and 8 µg/8 µg/2.5 µg, respectively. These differences result in more severe local adverse effects in vaccinees and would complicate booster strategies in Japan. Aligning Japan’s immunization policies with international practices represents a critical step toward ensuring individual health and public safety in increasingly globalized sports environments. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2051-3380 13 6 2025 Corynebacterium striatum-Associated Pyogenic Osteomyelitis With Direct Extension From Postoperative Empyema e70230 EN Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Corynebacterium striatum can cause postoperative empyema. C. striatum-associated empyema may be associated with osteomyelitis. Rifampicin is a viable therapeutic option for C. striatum infection. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2688-1152 6 1 2025 Severe Intracranial Infection 100026 EN Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Takumi Fujimori Microbiology Division, Clinical Laboratory, Okayama University Hospital Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

Public Library of Science (PLoS) Acta Medica Okayama 1932-6203 20 9 2025 Impact of COVID-19 on the awareness and interest in infectious disease specialization among Japanese medical students e0329451 EN Naruto Kamada Faculty of Medicine, Wakayama Medical University Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Satoshi Kutsuna Department of Infection Control and Prevention, Graduate School of Medicine, Osaka University Background The SARS-CoV-2 pandemic has highlighted the critical deficiency of infectious disease (ID) specialists, a subspecialty that remains underrepresented among Japanese medical students. Methods This nationwide cross-sectional survey was administered between April and August 2024 via an online questionnaire distributed to medical students throughout Japan. The survey assessed awareness of and interest in ID specialization, categorizing students by academic year: lower (first- and second-year students), middle (third- and fourth-year students), and upper grades (fifth- and sixth-year students). Results Of 502 respondents, data for 492 medical students were eligible, of whom 69.7% demonstrated awareness of ID specialists, with recognition rates increasing proportionally with academic progression. Regarding career aspirations, 9.8% of respondents expressed interest in pursuing ID specialization, with the highest proportion observed among upper-grade students (19.4%). Male students (14.8%) expressed greater interest in ID specialization than female students (5.2%). The pandemic positively influenced 5.5% of students to consider ID specialization as a future career, whereas only 0.6% reported a negative impact. Conclusions These findings underscore the necessity of enhanced educational initiatives to promote ID specialization among medical students, addressing current shortages and future infectious disease preparedness. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1083-7159 30 7 2025 Pharmacovigilance study for the identification of mogamulizumab-induced immune-related adverse events using a real-world database oyaf201 EN Koji Miyata Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University Yuki Izawa-Ishizawa Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University Takahiro Niimura Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University Toshihiko Yoshioka Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University Mizusa Hyodo Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University Shuto Itokazu Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University Tatsumi Miyata Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University Fuka Aizawa Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University Kenta Yagi Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University Kei Kawada Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Yoshito Zamami Department of Pharmacy, Okayama University Hospital Mitsuhiro Goda Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University Keisuke Ishizawa Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University Background: Mogamulizumab is a humanized anti-CCR4 monoclonal antibody used for relapsed/refractory adult T-cell leukemia, cutaneous T-cell lymphoma, and/or Sézary syndrome. Reports of immune-related adverse events (irAEs) in these patients are increasing, and the association between irAEs and mogamulizumab remains to be elucidated. This study aimed to evaluate the association between mogamulizumab and immune-related adverse events (irAEs), as well as to characterize the irAEs associated with mogamulizumab using data from a large-scale spontaneous reporting system. Methods: We performed an exploratory hypothesis-generating analysis of patients from 1967 to September 2023 using VigiBase, a World Health Organization spontaneous adverse event reporting system database. We performed a disproportionality analysis and determined the reporting odds ratios and information components between the drugs of interest and each irAE. Results: Mogamulizumab was associated with some irAEs, including myocarditis, severe cutaneous adverse reactions, hepatitis, and myositis. Mogamulizumab exhibited significantly higher reporting rates of these 4 irAEs compared to the anticancer agents other than mogamulizumab. Conversely, the reporting rate of other irAEs, including endocrine autoimmune diseases induced by immune checkpoint inhibitors, was not significant in patients who received mogamulizumab. Conclusions: Mogamulizumab is associated with irAEs, including myocarditis, severe cutaneous adverse reactions, hepatitis, and myositis. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 0925-5710 122 5 2025 Intravenous umbilical cord-derived mesenchymal stromal cell therapy may improve overall survival in Japanese patients with idiopathic pneumonia syndrome after hematopoietic stem cell transplantation: a multicenter, single-arm, phase II trial 733 743 EN Noriko Doki Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Shinichi Kako Division of Hematology, Jichi Medical University Saitama Medical Center Emiko Sakaida Department of Hematology, Chiba University Hospital Yoshinobu Kanda Division of Hematology, Department of Medicine, Jichi Medical University Idiopathic pneumonia syndrome (IPS) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT) and has a poor prognosis. Although IPS is often treated with steroids, the disease can become resistant to or dependent on steroid treatment, and there is no effective cure for patients with refractory or steroid-dependent IPS. This multicenter, open-label, single-arm, phase II clinical trial investigated the efficacy and safety of HLC-001 (allogeneic umbilical cord-derived mesenchymal stromal cells) in patients with progressive steroid-dependent or refractory IPS after HSCT. Seven male patients (all male; mean age: 43.3 years) received HLC-001 and three completed the trial. The survival rate at day 56 (primary endpoint) was 71.4% (5/7 patients; 95% confidence interval: 29.0%–96.3%) and was sustained at day 100, suggesting that HLC-001 was more effective than previously reported treatment. Three of the five patients with ≥ 100 days of follow-up died. Five patients experienced at least one adverse drug reaction, none of which were serious. These findings indicate that HLC-001 was potentially effective and generally well tolerated in Japanese patients with steroid-dependent or refractory IPS after HSCT. Given there is no effective cure for steroid-dependent or refractory IPS, HLC-001 may be a promising treatment option and further clinical evaluation is warranted. Trial registration: Japan Registry of Clinical Trials identifier: jRCT2063220014. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2575-6265 6 5 2025 Seaweed Extracts Improve Salinity Tolerance in Cereal Crops—A Meta‐Analysis e70094 EN Md. Nuruzzaman Department of Plant Resources, College of Industrial Sciences, Kongju National University Md. Tahjib‐Ul‐Arif Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University Md. Abdul Hannan Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University Yoshiyuki Murata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University M. Afzal Hossain Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University Seaweeds are considered an essential component of the blue economy. Because seaweed extracts are rich in bioactive compounds that enhance plant stress resilience, exploiting this resource could offer a sustainable solution for crop production. Salinity is a major abiotic challenge that significantly impacts crop yield and food security. Through meta-analysis, we explored whether the exogenous application of seaweed extracts improves the salt tolerance of cereal crops. All the studies chosen for this study utilized aqueous seaweed extracts as foliar sprays. A multi-level meta-analysis with a mixed effects model was performed to determine the effect size. This meta-analysis demonstrated that applying aqueous seaweed extracts enhanced the shoot and root biomass under normal and salinity stress conditions, suggesting that seaweed extract can help improve crop stress tolerance. The seaweeds studied belonged to three classes: Phaeophyceae, Rhodophyta, and Chlorophyta, with extracts from Chlorophyta and Phaeophyceae significantly enhancing biomass production under salinity conditions. Applying aqueous seaweed extracts effectively improved salinity tolerance at both 34.2–100 mM and 101–400 mM NaCl equivalent salinity stress. Moreover, exogenous foliar application of ≤ 25% aqueous seaweed extracts was most effective for improving salinity tolerance in cereals. The impact of seaweed extracts on cereal crop yields has not been extensively reported; therefore, further studies should focus on this aspect. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1340-6868 32 6 2025 Clinical significance on switching CDK4/6 inhibitors among 13,284 patients with metastatic breast cancer 1405 1416 EN Takuya Nishina Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Maki Tanioka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kenji Takada Medical AI Project, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takahiro Tsukioki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yuko Takahashi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tadahiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Recent clinical trials have shown that switching to a combination therapy of a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) prolongs progression-free survival (PFS) compared with ET monotherapy. Reports indicate that abemaciclib provides benefits regardless of the PIK3CA mutation status; however, its clinical benefits remain insufficient. This study aimed to evaluate the clinical significance of switching CDK4/6i + ET in a large real-world cohort. Using a medical database, we identified 13,284 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer who received CDK4/6i + ET between 2008 and 2022. Patients were categorized into five groups based on their first- and second-line therapy patterns. We compared the median time to discontinuation (TTD) among the groups. In patients who switched from one CDK4/6i + ET to another CDK4/6i + ET, the second-line TTD and total TTD of first- and second-line therapies (n = 542) were significantly longer than those in patients who switched from CDK4/6i + ET to ET monotherapy (n = 490) (the second-line TTD: 11.2 vs. 4.9 months, p < 0.01; total TTD: 25.1 vs. 20.5 months, p < 0.01). The order of palbociclib and abemaciclib administration did not significantly affect the second-line or total TTD in patients who switched from one CDK4/6i + ET to another CDK4/6i + ET. Switching from one CDK4/6i + ET to another CDK4/6i + ET resulted in a significantly longer TTD than switching to ET monotherapy. Considering the phase III clinical trial results of capivasertib, switching to CDK4/6i + ET is a viable therapeutic option regardless of the PIK3CA mutation status. No potential conflict of interest relevant to this article was reported.

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

Japanese Association of Rehabilitation Medicine Acta Medica Okayama 2432-1354 10 2025 Reliability and Validity of the Japanese Perme ICU Mobility Score: An Initial Psychometric Evaluation 20250037 EN Sho Katayama Department of Rehabilitation Medicine, Okayama University Hospital Tomohiro Ikeda Department of Rehabilitation Medicine, Okayama University Hospital Nobuto Nakanishi Department of Disaster and Emergency Medicine, Graduate School of Medicine, Kobe University Hajime Katsukawa Department of Scientific Research, Japanese Society for Early Mobilization Ricardo Kenji Nawa Department of Critical Care Medicine, Hospital Israelita Albert Einstein Christiane Perme Department of Rehabilitation Services, Houston Methodist Hospital Toshifumi Ozaki Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masanori Hamada Department of Rehabilitation Medicine, Okayama University Hospital Ikumi Sato Academic Field of Health Science, Okayama University Satoshi Hirohata Academic Field of Health Science, Okayama University Objectives : The Perme ICU Mobility Score is widely used to assess functional status, but no version of this assessment tool has been validated for use in Japan. This study aimed to translate the Perme Score into Japanese and evaluate its reliability and validity. Methods : Following forward–backward translation, the Japanese Perme Score was tested at ICU discharge. Inter-rater reliability was examined using weighted kappa coefficient. Construct validity was assessed through correlations with the Medical Research Council Sum Score (MRC-SS), Functional Status Score for the ICU (FSS-ICU), and ICU Mobility Scale (IMS). Predictive validity for activities of daily living (ADL) independence (Barthel Index ≥ 85) and discharge destination was evaluated using Receiver operating characteristic (ROC) analysis. Floor and ceiling effects were also analyzed. Results : In 69 patients, the Japanese Perme Score showed high inter-rater reliability (κ=0.83). It showed moderate correlation with FSS-ICU (rho=0.61) and IMS (rho=0.73), and it showed weak correlation with MRC-SS (rho=0.36). Predictive validity for ADL independence and home discharge yielded AUCs of 0.76 and 0.73, respectively. A ceiling effect was noted in 10% of cases, with no floor effect. Conclusions: The Japanese Perme Score is a reliable, valid instrument for evaluating physical function at ICU discharge. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2772-7076 14 2025 Genetic variability in Neisseria meningitidis strains isolated in a Japanese hospital 100511 EN Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Shinnosuke Fukushima Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Shuma Tsuji Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Osamu Matsushita Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objectives: Neisseria meningitidis is a significant pathogen causing invasive meningococcal disease, posing clinical and public health concerns worldwide. This study aimed to investigate the genetic characteristics of N. meningitidis clinical isolates at Okayama University Hospital in Japan. Methods: Between 2018 and 2023, five clinical strains were isolated, of which three were subjected to the antimicrobial susceptibility testing and whole genetic analysis using MiSeq platform (Illumina, San Diego, CA, USA). Results: One non-groupable isolate, belonging to sequence types (STs)-11026 (ST-32 complex), exhibited non-susceptibility to penicillin G, with a five-mutation pattern (F504L, A510V, I515V, H541N, and I566V) in the penA amino acid sequence and additional mutations (XXXIV and N513Y) characteristic of a mosaic penA gene. The other two isolates, ST-1655 (ST-23 complex) with serogroup Y and ST-2057 with serogroup B, were susceptible to penicillin G, neither of which contained the five-mutation pattern. Levofloxacin resistance was observed in two isolates carrying the T91I mutation in the gyrA protein. Conclusion: Our findings suggest the presence of antimicrobial-resistant N. meningitidis in Japan, underscoring the necessity for continuous local surveillance. Additional research is crucial for clarifying the ongoing spread of resistance mechanisms and for establishing effective countermeasures to reduce the clinical burden of invasive meningococcal disease. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 0066-4804 69 12 2025 Genomic portrayal of emerging carbapenem-resistant El Tor variant Vibrio cholerae O1 e00740-25 EN Sreeja Shaw ICMR-National Institute for Research in Bacterial Infections Agila Kumari Pragasam V. Ramalingaswami Bhawan, Indian Council of Medical Research Goutam Chowdhury ICMR-National Institute for Research in Bacterial Infections Prosenjit Samanta ICMR-National Institute for Research in Bacterial Infections Deboleena Roy ICMR-National Institute for Research in Bacterial Infections Debjani Ghosh ICMR-National Institute for Research in Bacterial Infections Thandavarayan Ramamurthy ICMR-National Institute for Research in Bacterial Infections Jigna Karia Medical College Baroda Govind Ninama Medical College Baroda Shin-ichi Miyoshi Okayama University Yukihiro Akeda National Institute of Infectious Diseases Hemanta Koley ICMR-National Institute for Research in Bacterial Infections Asish Kumar Mukhopadhyay ICMR-National Institute for Research in Bacterial Infections The escalating prevalence of carbapenem-resistant (CR) enteric pathogens elicits significant challenges to public health management and effective antimicrobial therapy. While carbapenem resistance is rare in Vibrio cholerae O1 (VC), the recent emergence of CR strains reveals a concerning shift in their antimicrobial resistance (AMR) landscape. This study aims to characterize the resistance mechanisms in newly identified El Tor CRVC isolated from cholera patients in Gujarat, India during 2019. Fifty VC isolates were screened for major virulence-associated genes along with the determination of their antibiotic resistance profiles using Kirby-Bauer disk diffusion and MIC assays. Whole-genome sequencing (WGS) was employed to investigate the underlying mechanisms of CR. All the isolates exhibited hypervirulent Haitian alleles of major virulence genes and AMR profiles of typical multidrug resistance (MDR). Strikingly, 12% (6/50) of them were resistant to carbapenems and other antibiotics. Molecular analysis revealed that these CR isolates were clonally related and harbored a 142 kbp IncA/C type conjugative mega-plasmid with several AMR encoding genes, including blaNDM-1, that can be easily transferred to other bacterial species and confer donor AMR patterns. The plasmid’s competence for horizontal gene transfer presents a significant risk of dissemination to other enteric pathogens and thereby may complicate the treatment. This finding emphasizes the urgent need for enhanced genomic surveillance and robust antimicrobial stewardship programs aimed at curbing the spread of CRVC strains and mitigating their impact on cholera treatment and containment strategies. No potential conflict of interest relevant to this article was reported.

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

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

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

Tech Science Press Acta Medica Okayama 1546-2226 85 2 2025 A Spectrum Allocation and Security-Sensitive Task Offloading Algorithm in MEC Using DVS 3437 3455 EN Xianwei Li School of Computer and Information Engineering, Bengbu University Bo Wei Faculty of Environmental, Life, Natural Science and Technology, Okayama University Xiaoying Yang School of Information Engineering, Suzhou University Amr Tolba Computer Science and Engineering Department, College of Applied Studies, King Saud University Zijian Zeng Institute of Computer Science and Digital Innovation, UCSI University Osama Alfarraj Computer Science and Engineering Department, College of Applied Studies, King Saud University With the advancements of the next-generation communication networking and Internet of Things (IoT) technologies, a variety of computation-intensive applications (e.g., autonomous driving and face recognition) have emerged. The execution of these IoT applications demands a lot of computing resources. Nevertheless, terminal devices (TDs) usually do not have sufficient computing resources to process these applications. Offloading IoT applications to be processed by mobile edge computing (MEC) servers with more computing resources provides a promising way to address this issue. While a significant number of works have studied task offloading, only a few of them have considered the security issue. This study investigates the problem of spectrum allocation and security-sensitive task offloading in an MEC system. Dynamic voltage scaling (DVS) technology is applied by TDs to reduce energy consumption and computing time. To guarantee data security during task offloading, we use AES cryptographic technique. The studied problem is formulated as an optimization problem and solved by our proposed efficient offloading scheme. The simulation results show that the proposed scheme can reduce system cost while guaranteeing data security. No potential conflict of interest relevant to this article was reported.