American Geophysical Union (AGU) Acta Medica Okayama 2169-9097 131 4 2026 Investigating the Detectability of Body Wave Phases From Tidal Ice Cracking Events on Titan With the Dragonfly Short-Period Seismometer e2025JE009432 EN L. Delaroque Université Paris Cité, Institut de Physique du Globe de Paris, CNRS T. Kawamura Université Paris Cité, Institut de Physique du Globe de Paris, CNRS A. Lucas Université Paris Cité, Institut de Physique du Globe de Paris, CNRS S. Rodriguez Université Paris Cité, Institut de Physique du Globe de Paris, CNRS K. Onodera Institute for Planetary Materials, Okayama University H. Shiraishi Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency R. Yamada The University of Aizu S. Tanaka Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency M. P. Panning Jet Propulsion Laboratory, California Institute of Technology R. D. Lorenz The Johns Hopkins University Applied Physics Laboratory Detecting seismic activity on Saturn's icy moon Titan during the Dragonfly mission could provide crucial information on its internal structure. The geological complexity of the moon's surface suggests significant cyclic tidal deformation, likely leading to the fracturing of the ice shell. Considering realistic source locations and fault geometries, we assess whether a vertical short-period seismometer can detect body waves from a Mw 4.0 icequake. Signal-to-noise ratios are evaluated by comparing the high-frequency content with the expected background noise and instrument capabilities for several ice attenuation scenarios and 1D interior models. Our results indicate that the high-frequency content (≥1Hz) of Mw≤4.0 tidal-induced icequakes is likely undetectable under the most unfavorable attenuation scenarios and atmospheric conditions. However, seismic signals in the 0.5–1 Hz band—where P wave reflections dominate—may still be observable for events occurring in potential seismically active regions at ∼800–1,000 km from the Dragonfly's landing site. These signals could provide constraints on the thickness of Titan's outer ice shell, provided that intrinsic attenuation is low and environmental conditions are favorable. No potential conflict of interest relevant to this article was reported.

Japan Medical Association Acta Medica Okayama 2433-3298 9 1 2026 Relationship between Maternal Body Composition during Pregnancy and Newborn Birth Weight in Japan 189 197 EN Eriko Eto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masakazu Kato Department of Obstetrics and Gynecology, 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 Chiaki Kuriyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shujiro Sakata Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hikari Nakato Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Sakurako Mishima Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akiko Ohira Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Introduction: This study aimed to investigate the changes in maternal body composition during pregnancy in Japanese women and the relationship between maternal body composition and newborn birth weight using pre-pregnancy body mass index (BMI) in all trimesters.<br> Methods: A total of 1,851 pregnant Japanese women were enrolled in this study. Body composition was measured using TANITA MC-190EM. The associations between newborn birth weight and maternal BMI, fat mass (FM), fat-free mass (FFM), total body water (TBW), muscle mass (MM), FM gain, FFM gain, and weight gain were evaluated.<br> Results: The participants’ age and pre-pregnancy BMI were 34.1 years and 21.4 kg/m2, respectively. Among the patients, 13.4%, 73.0%, 10.3%, and 3.3% were underweight, average weight, overweight, and obese, respectively. The FM showed no significant change from the second to third trimesters in the underweight, overweight, and obese groups. Moreover, the FM in the overweight and obese groups did not change during any period. The FFM, TBW, and MM significantly increased from the first to second and second to third trimesters. In BMI-stratified multivariate regression analyses, FFM in the normal and overweight groups was positively associated with birth weight, whereas FM gain was negatively associated in the underweight and normal groups. No significant associations were observed in the obese group.<br> Conclusions: Changes in maternal body composition during pregnancy in Japanese women varied by pre-pregnancy BMI. Associations with birth weight also differed by BMI group. Further prospective studies are needed to confirm these relationships and investigate the mechanisms. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 5 2026 Aerobic Exercise Attenuates Epidermal Hyperplasia in an Obesity-Associated Psoriasiform Dermatitis Model 2308 EN Yoshihiro Matsuda Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shin Morizane Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daiki Takezaki Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuma Sakamoto Department of Immunology and Molecular Genetics, Kawasaki Medical School Nobuyasu Baba Department of Immunology and Molecular Genetics, Kawasaki Medical School Masanori Iseki Department of Immunology and Molecular Genetics, Kawasaki Medical School Yoshio Kawakami Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tatsushi Shiomi Department of Pathology, Kawasaki Medical School Tomoyuki Mukai Department of Immunology and Molecular Genetics, Kawasaki Medical School Obesity is an important risk factor for psoriasis, and clinical studies indicate that exercise interventions can improve disease severity. However, the mechanisms by which exercise influences psoriatic pathogenesis remain insufficiently understood. To investigate the effects of aerobic exercise on obesity-associated psoriasis, wild-type mice were fed a high-fat diet (HFD) for 7 weeks to induce obesity and subsequently underwent moderate-intensity treadmill running for 3 weeks. Psoriasiform dermatitis was induced by daily topical application of imiquimod (IMQ) to the skin for five consecutive days. HFD increased body weight, epididymal fat mass, and serum cholesterol. HFD-fed mice developed more severe IMQ-induced psoriatic skin changes compared with normal diet-fed mice. Treadmill exercise modestly reduced body weight gain and attenuated epidermal hyperplasia in HFD-fed mice. In contrast, inflammatory cytokine expression, including Tnfa, Il17a, and Il23a, showed modest increases in the skin of HFD-fed exercised mice, which did not parallel the improvement in epidermal hyperplasia. Overall, these findings indicate that while obesity exacerbates psoriasiform dermatitis, aerobic exercise ameliorates epidermal hyperplasia in obese mice without corresponding changes in inflammatory cytokine expression in the skin, suggesting that exercise may influence psoriatic skin changes through multiple metabolic and immunological pathways. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2073-4360 18 7 2026 Effect of Universal Adhesives on Resin Cement–Fiber Post–Core Materials 810 EN Masao Irie Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiro Okada Department of Dental Biomaterials, Graduate School of Dentistry, Tohoku University Yukinori Maruo Department of Prosthodontics, Okayama University Kenraro Akiyama Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kumiko Yoshihara Health Research Institute, National Institute of Advanced Industrial Science and Technology Akimasa Tsujimoto Department of Operative Dentistry, School of Dentistry, Aichi Gakuin University Takuya Matsumoto Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University This study evaluated eleven resin cements used as core build-up materials by examining the following properties: (a) push-out force between root dentin and the fiber post; (b) pull-out force between the fiber post and the core build-up material; (c) shear bond strength of the resin cement to root dentin; (d) flexural strength of the resin cement; and (e) flexural modulus of elasticity of the resin cement. The purpose of this investigation was to clarify the relationships between recently available universal adhesives, core build-up materials, resin cements, and fiber posts. All experiments were performed at two evaluation periods: after 1 day of water storage (Base) and after 20,000 thermocycles (TC 20k). For the push-out test, simulated post spaces were prepared in single-rooted human premolars. The specimens were sectioned perpendicular to the long axis into 2 mm-thick slices and then subjected to push-out testing to assess the bond strength of the dentin–resin cement–fiber post complex. No significant differences in bonding performance were found between Base and TC 20k. These findings suggest that universal adhesives used for pretreatment of multiple substrates in fiber post cementation can provide not only strong but also durable adhesion over time. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1472-6831 26 1 2026 Evaluation of contact-active antibacterial properties of cetylpyridinium chloride–graphene oxide coatings on dental restorative and titanium surfaces: an in vitro study 558 EN Keisuke Okubo Department of Periodontics and Endodontics, Field of Medical Development, Okayama University Gen Kano Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masato Komoda Research Institute for Interdisciplinary Science, Okayama University Hideyuki Kamata Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin Nakamura Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Shinoda-Ito Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Omori Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Shogo Takashiba Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objective Biofilm formation on dental restorative materials and implant surfaces plays a central role in the development of dental caries, periodontal disease, and peri-implantitis. Durable antimicrobial surface treatments that inhibit bacterial adhesion and biofilm formation remain a significant unmet need in restorative and implant dentistry. Therefore, this study aimed to develop a composite coating combining cetylpyridinium chloride and graphene oxide, and to evaluate its durable antibacterial surface modification under in vitro conditions.<br> Methods A composite coating consisting of cetylpyridinium chloride and graphene oxide was prepared and applied to composite resin and titanium surfaces. Antibacterial activity against Streptococcus mutans and Porphyromonas gingivalis was evaluated using adenosine triphosphate assays and fluorescence-based live/dead staining. Coating retention after washing and air-drying was assessed by optical microscopy and Raman spectroscopy.<br> Results Cetylpyridinium chloride-graphene oxide-coated surfaces showed a significant reduction in bacterial viability compared with phosphate-buffered saline, ethanol, and cetylpyridinium chloride-only controls. Antibacterial effects were maintained after rinsing and air-drying on both composite resin and titanium surfaces. Raman spectroscopy confirmed the persistence of characteristic graphene oxide bands after washing, indicating stable retention of the coating on the material surfaces.<br> Conclusions Cetylpyridinium chloride–graphene oxide coatings demonstrate sustained surface-associated antibacterial activity against key cariogenic and periodontal pathogens and remain stably adhered to common dental restorative and implant materials after washing. These findings suggest that cetylpyridinium chloride–graphene oxide coatings may serve as a durable contact-active surface modification strategy to reduce biofilm formation associated with dental caries and peri-implantitis. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 7 2026 CXCR2-Dependent Infiltration of Tumor-Associated Neutrophils Is Linked to Enhanced CD8+ T Cell Effector Function and Reduced Lung Metastasis in 4T1 Breast Cancer 3143 EN Tiantian Li Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miao Tian Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Gakushi Nishida Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chunning Li Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Triple-negative breast cancer (TNBC) is characterized by prominent neutrophil infiltration; however, its significance remains controversial. Here, we investigated the role of neutrophil chemoattractant receptors in TNBC progression and metastasis. In contrast to wild-type (WT), Fpr1−/−, and Fpr2−/− mice, neutrophils were almost completely absent in 4T1 tumors from Cxcr2−/− mice, indicating a dominant role for CXCR2 in the recruitment of tumor-associated neutrophils, leading us to use Cxcr2−/− mice for further studies. Primary tumor growth was comparable between WT and Cxcr2−/− mice, whereas lung metastasis was significantly increased in Cxcr2−/− mice, with reduced expression of inflammatory cytokines, chemokines and cytotoxic molecules, including granzyme B and perforin, in primary tumors and metastatic lungs of Cxcr2−/− mice. In vitro, WT, but not Cxcr2−/−, neutrophils enhanced CD8+ T cell activation, partly via ICAM-1, and directly induced tumor cell death, supporting their anti-tumor function. To assess clinical relevance, transcriptomic data were analyzed. High neutrophil infiltration combined with elevated CXCR2 expression, and to a lesser extent CXCR1 expression, was associated with improved prognosis in patients with basal-like BC that largely overlaps with TNBC. Collectively, these findings suggest that CXCR2-mediated neutrophil recruitment exerts protective, anti-tumor effects and may represent a new prognostic marker for TNBC patients. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-2607 14 4 2026 The Role of Nitrate-Reducing Bacteria Isolated from Helicobacter pylori-Infected Individuals in Gastric Cancer Development 760 EN Serika Kuwagi Department of Bacteriology, Academic Field of Health Sciences, Okayama University Kazuyoshi Gotoh Department of Bacteriology, Academic Field of Health Sciences, Okayama University Marina Komatsubara Department of Bacteriology, Academic Field of Health Sciences, Okayama University Shuma Tsuji Department of Bacteriology, Academic Field of Health Sciences, Okayama University Shyoutarou Okanoue Department of Gastroenterology and Hepatology, Academic Field of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Okada Himeji Red Cross Hospital Jumpei Uchiyama Department of Bacteriology, Academic Field of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Akari Watanabe Department of Oral Health Care and Rehabilitation, Institute of Biomedical Sciences, Graduate School, Tokushima University Kenji Yokota Department of Bacteriology, Academic Field of Health Sciences, Okayama University Helicobacter pylori is a Gram-negative bacterium that inhabits the gastric mucosa, with a global prevalence in humans of approximately 40%. It is likely the cause of 90% of gastric cancer (GC) cases and thus considered the most prominent driver of GC development. However, during gastric mucosal atrophy, other bacteria such as nitrate-reducing bacteria (NRB) also proliferate. In this study, we isolated NRB from patients with gastritis and GC to examine their effects on the epithelial cell cycle and production of various cytokines in monocytic cell lines. Bacterial counts (excluding H. pylori and NRB) increased with the progression of gastric mucosal atrophy and were significantly higher in patients with GC. Gastric epithelial cell lines were stimulated with isolated NRB, and the proportion of cells in each cell cycle was measured. Strains from patients with open-type gastritis progressed more rapidly through cell cycles than those from patients with GC. NRB isolated from gastric cancer had high nitrate-reducing activity. Thus, NRB may contribute to GC progression during H. pylori-induced carcinogenesis. Therefore, evaluating gastric atrophy and microbiota may be important for managing the risk of GC. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0971-5894 2026 Suppression of salt-enhanced apoplastic flow by salicylic acid in rice EN Md. Asadulla Al Galib Graduate School of Environmental and Life Science, Okayama University Maoxiang Zhao Graduate School of Environmental and Life Science, Okayama University Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Yoshihiko Hirai Graduate School of Environmental and Life Science, Okayama University Yoshitaka Nakashima Graduate School of Environmental and Life Science, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Izumi C. Mori Institute of Plant Science and Resources, Okayama University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Salinity enhances apoplastic flow, resulting in an increment of Na+ uptake and a lower K+/Na+ ratio. Salicylic acid (SA) plays an important role in improving salinity tolerance in plants. The effect of exogenous SA on apoplastic flow in salt-treated rice seedlings was studied using an apoplastic tracer, 8-hydroxy-1,3,6-pyrenetrisulphonic acid (PTS) in light. Application of NaCl at 25 mM to the hydroponic solution significantly increased PTS uptake, while 25 mM NaCl did not affect seedling growth. Application of 25 mM NaNO3 increased PTS uptake to the same degree. Salinity significantly increased sodium (Na+) content but had no significant effect on potassium (K+) content, resulting in a lower K+/Na+ ratio. The application of SA at 0.05 mM and 0.1 mM to the hydroponic solution reduced Na-enhanced PTS uptake. Salicylic acid at 0.05 mM and 0.1 mM significantly reduced Na+ content and slightly increased K+ content in the shoots of rice seedlings, resulting in a higher K+/Na+ ratio. However, SA at up to 0.1 mM did not increase SA contents in shoots under salt stress. These results suggest that exogenous SA reduces Na+ uptake by suppressing Na+-enhanced apoplastic flow in rice seedlings. These findings provide insight into modulation of Na+ transport pathways from roots to shoots by SA and may allow us to utilize brackish water for rice cultivation and to improve salt-tolerant rice through suppression of salt-enhanced apoplastic flow by chemicals such as salicylic acid. No potential conflict of interest relevant to this article was reported.

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

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.

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

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

MDPI AG Acta Medica Okayama 2076-3417 16 5 2026 Concentration-Dependent Synergistic Interfacial Interactions Between Multifunctional Acrylate and Silane Coupling Agents in an Organic–Inorganic Nanohybrid Material 2339 EN Yukinori Maruo Department of Prosthodontics, Okayama University Kumiko Yoshihara Health Research Institute, National Institute of Advanced Industrial Science and Technology Masao Irie Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama University Naoki Kodama Department of Prosthodontics, Okayama University Mai Yoshizane Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kentaro Akiyama Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Synergistic effects of a multifunctional acrylate and a long-chain silane coupling agent were investigated in an organic–inorganic nanohybrid material. We tested the bond strength of nanohybrid composites treated with experimental primers containing silane coupling agents—3-methacryloxypropyl trimethoxysilane (γ-MPTS) or 8-methacryloxyoctyl trimethoxysilane (8-MOTS)—with or without multifunctional acrylates—trimethylolpropane triacrylate (A-TMPT) or dipentaerythritol hexaacrylate (A-DPH). Shear bond strength was evaluated after 24 h of water storage at 37 °C. Untreated control and silane-only groups exhibited low shear bond strengths (e.g., control: 2.4 ± 2.0 MPa) and failed exclusively at the adhesive interface. While addition of A-TMPT did not significantly improve bond strength, addition of A-DPH produced significantly higher shear bond strengths. Highest strength was achieved with 30% 8-MOTS and A-DPH (22.4 ± 6.1 MPa), followed by 20% γ-MPTS and A-DPH (19.0 ± 7.0 MPa), and A-DPH groups produced cohesive failures. Regardless of the silane used (γ-MPTS or 8-MOTS), incorporating A-DPH in the primer consistently yielded superior bond strengths, indicating a promising strategy for improved adhesion for such nanohybrid systems. These findings provide new insights into optimizing resin–filler interfacial interactions and may contribute to the development of restorative materials with improved long-term clinical durability. No potential conflict of interest relevant to this article was reported.

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

JMIR Publications Inc. Acta Medica Okayama 2369-3762 12 2026 Prescription Support Practice for Pharmacy Students: Pre-Post Educational Intervention Study e79545 EN Fuka Aizawa Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Kenta Yagi Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University Tsukasa Higashionna Department of Pharmacy, Okayama University Hospital Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Shimon Takahashi Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Kazuaki Shinomiya Department of Pharmaceutical Care and Clinical Pharmacy, Tokushima Bunri University Takahiro Niimura Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Mitsuhiro Goda 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 Keisuke Ishizawa Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Background: In the field of team-based care, pharmacists are vital for optimizing medication therapy. However, many medical professionals lack the opportunity to learn how to propose prescription changes with precision.<br> Objective: This study aimed to address this knowledge gap by developing and assessing a new educational program for pharmacy students focused on prescription support and interprofessional collaboration.<br> Methods: We recruited 191 fifth-year pharmaceutical students during the 2022‐2024 academic years. The program featured a 7-day intensive curriculum that included learning how to assist with prescriptions, analyzing clinical data, and engaging in role-playing exercises. A web-based questionnaire and a paper test were used to evaluate students’ awareness and knowledge both before and after the program. Statistical analyses were performed to verify the significance of changes; we utilized the Wilcoxon signed-rank test for the ordinal data derived from the specific behavioral objectives and 2-tailed paired t tests for the interval data from the knowledge tests. The magnitude of change was quantified using r for Wilcoxon tests and Cohen dz for 2-tailed t tests, with 95% CI calculated to ensure the stability and reliability of the observed results.<br> Results: Analysis of the primary outcome specific behavioral objectives revealed statistically significant effects across all items (Wilcoxon signed-rank test; P<.001). Effect sizes (r=0.505‐0.835) ranged from moderate to large, with particularly large effects observed in identifying contents issue (r=0.835, 95% CI 0.126-0.330; P<.001). Knowledge test scores showed significant improvement in the following 3 subjects: pharmacology (r=−0.504, 95% CI –0.215 to 0.127; P<.001), organic chemistry (r=0.254, 95% CI –0.148 to –0.193; P=.004), and communication (r=0.221, 95% CI –0.151 to –0.190; P=.01). No significant changes were observed in pathology or pharmacokinetics.<br> Conclusions: This program provides strong evidence that practical, hands-on learning with hospital pharmacists helps improve pharmacy students’ professional skills and optimize pharmaceutical therapies in interprofessional care. By teaching pharmacists to effectively propose prescription changes, the program equips them to become integral members of interprofessional care, ultimately leading to optimized pharmaceutical care for patients. 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 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.<br> 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.<br> 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.<br> 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.

Springer Science and Business Media LLC Acta Medica Okayama 1863-9941 52 1 2026 Preferential sacral fracture sites in fragility fractures of the pelvis type IVb and comparison of internal fixation methods: CT-based morphological mapping and finite element analysis 72 EN Shuichi Naniwa Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masanori Yorimitsu Department of Musculoskeletal Traumatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Tsubasa Hasegawa Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teruhiko Ando Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuichiro Okuda Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shiro Fukuoka Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital Yusuke Mochizuki Department of Emergency Health Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuaki Yamakawa Department of Orthopaedic Surgery, Kochi Health Sciences Center Ryuichi Nakahara Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shiro Hanakawa Department of Orthopaedic Surgery, Okayama Saidaiji Hospital Toshifumi Ozaki Department of Orthopedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose Fragility fractures of the pelvis (FFP) classified as Rommens-Hoffman type IVb are associated with spinopelvic dissociation and are generally considered to require surgical intervention. This study aimed to clarify the localization patterns of FFP type IVb and compare the biomechanical stability of different internal fixation techniques.<br> Methods In this retrospective study, morphologic mapping of sacral fracture lines was performed in 36 patients with FFP type IVb. Based on the mapping results, a finite element (FE) model of FFP type IVb was developed to evaluate the biomechanical stability of ilio-sacral screw (ISS) fixation, trans-sacral screw (TSS) fixation, spinopelvic fixation (SPF; On each side, L5 pedicle screw was connected to two iliac screws with a rod, and the bilateral constructs were linked using a cross-connector.), and bilateral triangular fixation (one TSS at S1 combined with SPF mentioned above) using finite element analysis (FEA).<br> Results Morphologic mapping showed that the sacrum fracture transverse line tended to pass between the S1-2 transverse lines. Although bilateral triangular fixation and SPF provided the highest stability in both U-type and H-type fractures, a TSS for U-type and two TSSs for H-type also demonstrated comparable levels of stability. ISS-based methods showed greater displacements.<br> Conclusion TSS-based fixation may provide stability comparable to bilateral triangular fixation and SPF in FFP type IVb, with less invasiveness when anatomy permits. Further studies are needed to optimize treatment strategies for this complex injury. 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.<br> 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.<br> 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).<br> 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 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 &amp; Pharmaceutical Science, Okayama University Takehiro Tanaka Department of Pathology and Oncology, Graduate School of Medicine, Dentistry &amp; Pharmaceutical Science, Okayama University Riri Mishima Department of Pathology and Oncology, Graduate School of Medicine, Dentistry &amp; 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 &amp; 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.<br> 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.<br> 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.

Wiley Acta Medica Okayama 2577-171X 9 2 2026 Mitrofanoff Appendicovesicostomy With Boari Flap for Complete Female Urethral Transection: A Case Report e70154 EN Kohei Mori Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Iwata Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsushi Kawada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Tominaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuichiro Yamasaki Department of Urology, Kanagawa Children's Medical Center Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction: Female urethral complete transection caused by pelvic trauma is extremely rare, and no standard management has been established when urethral reconstruction is not feasible.<br> Case Presentation: A woman in her twenties sustained an open pelvic fracture with perineal injury due to a traffic accident. Complete urethral transection was identified, and a suprapubic cystostomy was placed. After staged vaginal reconstruction and bladder function evaluation, a Mitrofanoff appendicovesicostomy was performed. Because the appendix was not enough to reach the umbilicus, a Boari flap was created to compensate for the length. Urodynamic evaluation showed improvement from a preoperative high-pressure bladder to increased compliance postoperatively, though pharmacological management was still required. Postoperatively, the patient achieved stable clean intermittent catheterization without complications.<br> Conclusion: The Mitrofanoff procedure can be an effective option in female urethral injuries where reconstruction is impossible. The addition of a Boari flap may expand its applicability by overcoming conduit length limitations. 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.

American Society for Horticultural Science Acta Medica Okayama 0018-5345 61 2 2026 Interactive Effects of Maximum Daytime and Minimum Nighttime Temperatures on Spinach Growth and Physiological Characteristics 444 451 EN Nethone Samba Faculty of Food and Agricultural Sciences, Fukushima University Hisao Akasaka The United Graduate School of Agricultural Sciences, Iwate University, Iwate, 020-8550, Japan; and Iwate Agricultural Research Center, Kenpoku Agricultural Research Institute Ken-ichiro Yasuba Graduate School of Environmental and Life Science, Okayama University Tanjuro Goto Graduate School of Environmental and Life Science, Okayama University Minori Hikawa-Endo Graduate School of Environmental and Life Science, Okayama University Yoko Miyama Faculty of Food and Agricultural Sciences, Fukushima University, Fukushima, 960-1296, Japan; and The United Graduate School of Agricultural Sciences, Iwate University High temperatures restrict spinach growth, and the plant’s growth and physiological responses to heat remain poorly understood. It remains unclear whether high daytime or elevated nighttime temperatures have a more negative impact on spinach growth. In addition, the interaction effect of maximum daytime and minimum nighttime temperatures on spinach growth remains unknown. This study was conducted to address these issues. Spinach was grown in controlled environments under four temperature treatments: 30 and 20 °C (T30/20), 30 and 25 °C (T30/25), 35 and 20 °C (T35/20), and 35 and 25 °C (T35/25). These treatments represent the maximum daytime temperature and minimum nighttime temperature, respectively, and were maintained for 45 days. Plant growth characteristics were monitored, and the physiological responses to temperature regimes were assessed. The results show that compared with T30/20, dry matter production decreased by 15.4% with increased nighttime temperature (T30/25), decreased by 42.3% with increased daytime temperature (T35/20), and decreased by 57.7% when both daytime and nighttime temperatures were increased (T35/25). However, there was no statistically significant interaction effect (P > 0.05) between daytime maximum and nighttime minimum temperatures on plant biomass production variables. In comparison with T30/20, the T35/25 treatment increased significantly plant stomatal conductance, stomatal apertures, transpiration rate, and leaf temperature during heat waves. The T35/25 treatment also decreased the quantum efficiency in light compared with the other treatments. Plant biomass production did not improve with the T35/20 and T35/25 treatments, likely as a result of a decoupling of photosynthesis and stomatal conductance during heat waves. Overall, these results reveal that maximum daytime and minimum nighttime temperatures exert additive effects on spinach growth. 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.

MDPI AG Acta Medica Okayama 1999-4923 18 1 2026 Streamlined Radiosynthesis of [18F]Fluproxadine (AF78): An Unprotected Guanidine Precursor Enables Efficient One-Step, Automation-Ready Labeling for Clinical Use 123 EN Xinyu Chen Nuclear Medicine, Faculty of Medicine, University of Augsburg Kaito Ohta Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Kimura Agency for Health, Safety and Environment, Kyoto University Yusuke Yagi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takanori Sasaki Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoko Nose Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaru Akehi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiko Yamane Department of Molecular Imaging Research, Kobe City Medical Center General Hospital Rudolf A. Werner Department of Nuclear Medicine, LMU Hospital, and German Cancer Consortium (DKTK), Partner Site Munich, Ludwig-Maximilians-University of Munich Takahiro Higuchi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: [18F]Fluproxadine (formerly [18F]AF78) is a PET radiotracer targeting the norepinephrine transporter (NET) with potential applications in cardiac, neurological, and oncological imaging. Its guanidine moiety, while essential for NET binding, presents major radiosynthetic challenges due to high basicity and the harsh deprotection conditions required for protected precursors. Previous methods relied on multistep procedures, strong acids, and complex purification, limiting clinical translation. This study aimed to develop a practical one-step radiosynthesis suitable for routine and automated production. Methods: A direct SN2-type nucleophilic [18F]fluorination was performed using an unprotected guanidine precursor to eliminate deprotection steps. Reaction parameters, including the base system, solvent composition, precursor concentration, and temperature, were optimized under conventional and microwave heating. Radiochemical conversion (RCC) and operational robustness were evaluated, and purification strategies were assessed for automation compatibility. Results: Direct [18F]fluorination using the unprotected precursor reduced the total synthesis time to 60–70 min. Optimal conditions employed a tert-butanol/acetonitrile (4:1) solvent system with K2CO3/Kryptofix222, affording RCC up to 33% under conventional heating. Microwave irradiation further improved efficiency, achieving RCC of up to 64% within 1.5 min at 140 °C. The method showed broad tolerance to variations in the base molar ratio and precursor concentration and enabled isocratic HPLC purification. Conclusions: This one-step radiosynthesis overcomes longstanding challenges in [18F]fluproxadine production by eliminating harsh deprotection and enabling high-yield, automation-ready synthesis, thereby improving clinical feasibility. No potential conflict of interest relevant to this article was reported.

Institute of Electrical and Electronics Engineers (IEEE) Acta Medica Okayama 2169-3536 14 2026 FEM-Based Design and Characterization of a Millimeter-Scale Piezoelectric Resonance Force Sensor 17960 17970 EN Aoto Yamazaki Department of Mechanical Engineering, Toyohashi University of Technology Takuma Akiduki Department of Mechanical Engineering, Toyohashi University of Technology Atsuo Honna Riccoh Company Ltd. Michiteru Kitazaki Department of Computer Science and Engineering, Toyohashi University of Technology Tomoaki Mashimo Graduate School of Natural Science and Technology, Okayama University This paper presents a millimeter-scale piezoelectric effect-based force sensor that uses the change in its resonant frequency as the detection principle for high sensitivity and a wide measurement range. Such characteristics are suited for robot hand applications that not only detect small forces but also handle large payloads. We develop a methodology to estimate the relationship between applied force and resonant frequency shift by combining classical contact theory and finite element method (FEM) analysis. Although this relationship is non-linear, the designability of sensitivity and measurement range is demonstrated by the simulation. The simulation results based on the method are verified, showing good agreement with the experimental results. The static characteristics, including sensitivity, standard deviation, and resolution, are evaluated using prototype sensors with characteristic lengths ranging from 1 mm to 4 mm. The 4-mm model has a measurement range of 77 mN to 300 N, and the smallest model, which is one of the smallest force sensors suitable for practical implementation, has a measurement range of 9 mN to 20 N. 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 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.<br> 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.<br> 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.<br> 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.

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.<br> 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.<br> 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.<br> 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.

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 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.

MDPI AG Acta Medica Okayama 2077-0383 15 5 2026 Effect of Surgical Procedures for Rheumatoid Forefoot Deformities on Radiographic Foot Length and Width Variations 1877 EN Masahiro Horita Department of Orthopaedic Surgery, Faculty of Medical Development Field, Okayama University Yohei Kiso Department of Orthopaedic Surgery, Kurashiki Sweet Hospital Yoshihisa Nasu Department of Orthopaedic Surgery, Okayama City Hospital Ryuichi Nakahara Department of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenta Saiga Department of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichiro Nishida Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Background: The number of patients with rheumatoid arthritis (RA) undergoing forefoot arthroplasty has increased to better control the disease. Despite patients frequently expressing concerns regarding postoperative foot appearance and footwear-related expectations, no study has investigated postoperative changes in foot length and width in patients with RA. The aim of this study was to evaluate the effect of surgical procedures for rheumatoid forefoot deformities on variations in radiologically determined foot length and width. Methods: In total, 72 feet of 50 women and 3 men (average age: 66.7 years) underwent joint-preserving arthroplasty (n = 33) and arthrodesis of the first metatarsophalangeal joint with shortening osteotomy of the lesser metatarsals or resection arthroplasty of the lesser metatarsal heads (n = 39); procedures were carried out in our institute from August 2013 to February 2020. The mean disease duration was 23.5 years, and the average follow-up period was 17.5 months. Pre- and postoperative hallux valgus angle (HVA), intermetatarsal angle (IMA) of the first and second metatarsals (M1M2A), and IMA of the first and fifth metatarsals (M1M5A) were measured on weightbearing radiographs as well as foot length and width. We also evaluated the correlation between changes in radiographic parameters and variations in radiologically determined foot length and width. Results: Radiologically determined foot width changed significantly from 10.1 cm to 9.7 cm (p < 0.01), while no significant difference was found between pre- and postoperative radiologically determined foot length. HVA, M1M2A, and M1M5A were significantly improved after the surgery (p < 0.01, p < 0.01, and p < 0.01, respectively). A significant negative correlation was found between the variation in radiologically determined foot length and changes in HVA (r = −0.29, p = 0.02) and M1M5A (r = −0.23, p < 0.05), while a significant positive correlation was found between the variation in the foot width and changes in HVA (r = 0.34, p < 0.01), M1M2A (r = 0.55, p < 0.01), and M1M5A (r = 0.45, p < 0.01). There were no significant differences between operative procedures regarding variation in radiologically determined foot length and width. Conclusions: Surgical procedure for rheumatoid forefoot deformity improved radiographic parameters and reduced radiographic foot width while maintaining foot length. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2079-7737 15 5 2026 Alpha-Ketoglutarate Drives an Osteogenic and Extracellular Matrix Gene Program in Periodontal Ligament Fibroblasts via Selective Reduction of H3K27me3 372 EN Ryu Hasegawa Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Shigeki Suzuki Department of Operative Dentistry, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences Rahmad Rifqi Fahreza Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Shin-Ho Tsai Department of Operative Dentistry, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences Yoshino Daidouji Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Masato Omori Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Tetsuhiro Kajikawa Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Satoru Yamada Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry Periodontal disease damages the tissues that support teeth and can ultimately lead to tooth loss, yet effective treatments to regenerate these tissues are still limited. Recent studies have shown that substances produced during normal cellular metabolism can influence how genes are regulated, but their role in periodontal regeneration has not been fully clarified. In this study, we investigated whether alpha-ketoglutarate, a naturally occurring metabolite involved in energy production, could promote periodontal tissue regeneration. We found that alpha-ketoglutarate enhanced bone-related and extracellular matrix-related gene expression in human periodontal ligament cells by reducing a repressive gene-regulatory signal that normally suppresses these genes. Importantly, alpha-ketoglutarate did not broadly alter chromatin accessibility, indicating that its effects were mediated through selective gene regulation. Furthermore, oral administration of alpha-ketoglutarate promoted alveolar bone regeneration and collagen-rich tissue formation in a mouse model of periodontal disease. Because alpha-ketoglutarate is a naturally occurring molecule in the body, these findings suggest that metabolite-based regulation of gene activity may represent a promising and safe approach for periodontal tissue regeneration. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 18 4 2026 Antigen Remodeling in Colorectal Cancer: How Radiotherapy and Chemotherapy Enhance Immunotherapy Responsiveness 715 EN Yuki Matsumi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiaki Takahashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Moriwake Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masashi Kayano Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Colorectal cancer (CRC) is traditionally considered a “cold tumor” characterized by low immunogenicity and limited responsiveness to immune checkpoint inhibitors (ICIs). However, recent findings reveal that cytotoxic modalities can reprogram this immunologically inert landscape. This review integrates these evolving concepts to guide the optimization of future treatments. Radiotherapy induces extensive DNA double-strand breaks, which may generate de novo mutations through error-prone repair while simultaneously exposing cryptic antigens via increased transcriptional instability, alternative splicing, and enhanced proteasomal processing. Chemoradiation also amplifies epigenetic and epitranscriptomic sources of neoepitope diversity, including RNA editing and stress-induced splicing alterations, expanding the immunopeptidome beyond canonical mutation-driven neoantigens. These changes collectively enhance antigen presentation and facilitate T-cell priming. Chemotherapy further reduces immunosuppressive cell populations and promotes dendritic cell activation, creating a permissive milieu for subsequent immune engagement. Clinically, the VOLTAGE studies demonstrated that long-course chemoradiotherapy can sensitize even mismatch repair–proficient rectal cancers to PD-1 blockade, yielding clinically meaningful pathological responses. In contrast, mismatch repair–deficient rectal tumors may respond completely to ICIs alone. Short-course radiotherapy combined with chemotherapy and ICIs has also shown encouraging activity in the setting of total neoadjuvant therapy. Collectively, these findings support a paradigm in which radiotherapy, chemotherapy, and epigenetic/epitranscriptomic alterations—including RNA editing—act as potent modulators of tumor antigenicity. By expanding the neoantigen repertoire and reshaping the tumor microenvironment, these strategies can transform CRC from a cold tumor into one that is increasingly responsive to immunotherapy. No potential conflict of interest relevant to this article was reported.

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

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.<br> Materials and methods: A total of 106 patients with thymic carcinoma underwent curative intended resection at 19 institutions between January 2010 and December 2021. Excluding 14 patients with incomplete resection, 92 patients with thymic carcinoma who underwent total (n = 73) or partial thymectomy (n = 19) were compared. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan–Meier curves and Cox proportional hazard models. Overlap weighting was applied to adjust for potential confounding factors.<br> Results: Among patients with clinical stage I disease, 79.3% were upstaged to stage II or higher postoperatively. Unadjusted analyses revealed no statistically significant differences in OS and RFS between the total and partial thymectomy groups, although a trend toward poorer outcomes in the partial thymectomy group was observed. After overlap weighting, partial thymectomy was associated with significantly poorer OS (P = 0.0027) and higher recurrence risk (P < 0.0001). Early postoperative recurrence occurred more frequently in the partial thymectomy group.<br> Conclusion: Partial thymectomy was associated with significantly worse survival and recurrence outcomes in thymic carcinoma. Given the limitations of preoperative diagnosis, total thymectomy should remain the preferred surgical approach for undiagnosed thymic epithelial tumors to achieve optimal oncologic control and minimize the risk of recurrence. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0007-1188 2026 Induction of IL-9-producing CD8+ T cells by ascochlorin derivatives EN Natsumi Imano Department of Immunology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Mikako Nishida Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Miho Tokumasu Department of Immunology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Weiyang Zhao Department of Immunology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Nahoko Yamashita Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Heiichiro Udono Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Background and Purpose: Ascochlorin (ASC) is an antiviral antibiotic from the fermented broth of Ascochyta viciae which exerts an inhibitory effect to cancers. Its impact on immune cells has not been examined. In this study, we obtained ASC derivatives with less cytotoxicity and determined whether they affected T cells, indicating possible immune-mediated antitumour effects.<br> Experimental Approach: Newly synthesised ASC derivatives were screened for inhibitory effects on T-cell antigen receptor (TCR)-stimulated proliferative responses using murine CD4+ and CD8+ T cells. Two compounds were identified that exhibited >10-fold less toxicity compared with ASC. N184, the less toxic of the two, was analysed for its in vivo antitumour effects, and in vitro effects on CD8+ T-cell proliferation, survival, cytokine production and exhaustion, using microscopy, qPCR and flow cytometry.<br> Key Results: N184 induced limited IL-9 production in CD8+ T cells following TCR stimulation, thereby improving cell survival. It also enhanced cytokine production in the late phase of proliferation and suppressed the induction of exhaustion. N184 suppressed tumour growth in mice in a CD8+ T cell-dependent manner. The effect was partially prevented by an IL-9-neutralising antibody.<br> Conclusion and Implications: N184 induces differentiation of IL-9-producing CD8+ T cells in vitro and elicits antitumour immunity in an IL-9-dependent manner. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 2235-2988 15 2026 Binding of IgA1 and surface-expressed collagen-binding protein of Streptococcus mutans contributes to IgA nephropathy pathogenesis 1673581 EN Daiki Matsuoka Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kana Suehara Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Naka Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Taro Misaki Division of Nephrology, Seirei Hamamatsu General Hospital Yasuyuki Nagasawa Department of General Internal Medicine, Hyogo Medical University Seigo Ito Department of Internal Medicine, Japan Self-Defense Force Iruma Hospital Yuto Suehiro Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka Ryota Nomura Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University Kazuhiko Nakano Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka Michiyo Matsumoto-Nakano Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: The present study was conducted to examine the interaction between collagen-binding protein (Cnm) of Streptococcus mutans and immunoglobulin (IgA) to clarify the possible involvement in IgA nephropathy (IgAN) development.<br> Methods: The binding of Cnm to human immunoglobulins was examined using an enzyme-linked immunosorbent assay. A nephritis-induced rat model was employed to confirm the localization of Cnm.<br> Results: IgA1 showed significantly greater binding ability to Cnm than to other bacterial surface proteins, and Cnm showed significantly greater binding ability to IgA1 than to other immunoglobulins. In rats administered Cnm, IgA deposition was observed in the glomerular mesangial region. Furthermore, biotin-labeled Cnm was observed in the same region as IgA deposition in the Cnm group.<br> Conclusions: Taken together, it is considered that following invasion into the bloodstream, Cnm binds to and forms a complex with IgA1, leading to deposition of IgA1 in renal glomeruli. 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.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Metastatic Intraocular Tumor Likely from Hepatocellular Carcinoma Mimicking Panuveitis 63 67 EN Eri Takasu Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Shiode Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroya Kindo Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Kimura Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mio Hosokawa Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Kanzaki Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuro Morita Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Adachi 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 Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/70074 A 77-year-old man undergoing treatment for hepatocellular carcinoma (HCC) presented with blurred vision in his right eye, persisting for 2 months. Slit-lamp microscopy and fundus examination revealed inflammatory cells in the anterior chamber, severe vitreous opacities, and retinal vasculitis in the right eye. The patient underwent vitreous surgery with biopsy, and vitreous cytology confirmed a metastatic intraocular tumor originating from the HCC. Radiotherapy was administered to the right eye, with no recurrence of intraocular inflammation observed at 10 months post-irradiation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Changes in Prescribing Patterns of Antiviral Drugs before and after Public Coverage Termination among Hospitalized COVID-19 Patients in Regional Hospitals in Japan: A Retrospective, Multicenter Study 55 62 EN Hidemasa Akazawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Shohei Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Yasuhiro Nakano 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, Original Article 10.18926/AMO/70073 In Japan, antiviral agents for COVID-19 were freely available until September 2023 as part of national policy. This study evaluated changes in these agents’ prescribing patterns and the patient outcomes following the policy shift. We conducted a multicenter retrospective study at four hospitals in Japan’s Okayama and Kagawa prefectures from January 2022 to March 2024. The study period was divided into the public-expenditure phase (January 2022 to September 2023) and the post-expenditure phase (October 2023 to March 2024). We extracted the hospitalized patients’ clinical data from the electronic database. The study’s primary outcome was the antiviral prescription rate; the secondary outcome was in-hospital mortality. Among the 302 hospitalized patients (median age 85 years), 52.0% were classified as having a mild condition. Of the patients with mild conditions, 37.7% were diagnosed in outpatient settings prior to hospitalization. During the public-expenditure phase, 47.4% of the patients received antivirals as outpatients, mainly molnupiravir (80.9%). In the post-expenditure period, 80.0% of the patients were prescribed antivirals, mostly molnupiravir (91.7%). The antiviral prescription rate was significantly higher after the policy change. The overall in-hospital mortality was 15.8%, with no significant difference between the two periods (17.0% vs. 10.5%). Despite the termination of government funding, antiviral prescriptions remained frequent at community hospitals located in highly aging regions of western Japan such as Okayama and Kagawa prefectures. Mortality remains high among the elderly, highlighting the need for continued antiviral therapy and booster vaccinations. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Time Course of the Development and Loss of Delta-9-tetrahydrocannabinol Tolerance: Effects on Hypothermia and Spontaneous Locomotor Activity in Mice 47 54 EN Yukiomi Eguchi Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Soichiro Ushio Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Keiichi Irie Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Yuta Yamashita Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Miyu Eguchi Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Takafumi Nakano Department of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Kenichi Mishima Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University Original Article 10.18926/AMO/70072 Deregulation of cannabis use is gradually expanding in Europe and the United States. However, the biological processes driving tolerance to delta-9-tetrahydrocannabinol (Δ9-THC), the main psychoactive component of cannabis, remain unclear. Thus, this study aimed to investigate the mechanisms and time course of tolerance development and loss to Δ9-THC in mice. Male ICR mice (7 weeks old) were administered Δ9-THC once daily for 3 days and then divided into three groups according to the washout period (3-, 10-, and 17-day washout groups). After each washout, changes in body temperature and locomotor activity were measured following re-exposure to Δ9-THC. Furthermore, the mRNA expression levels of CB1 and CB2 receptors in the brain were evaluated using real-time PCR. On day 1, significant hypothermia and reduced spontaneous locomotor activity were observed in the Δ9-THC-treated mice compared with the vehicle-treated mice. Tolerance to the hypothermic and locomotor-suppressing effects of Δ9-THC developed on days 2 and 3, respectively, and dissipated after 3 and 11 days of washout, respectively. These differences in the rates of tolerance development and recovery may reflect distinct underlying mechanisms. No significant changes in receptor mRNA expression were observed. These findings highlight the complexity of Δ9-THC tolerance and its potential implications for long-term cannabis use. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Kinesiophobia Is Associated with Disability, Poor Quality of Life, Psychological Morbidity, and Surgery Dissatisfaction in Patients with Lumbar Microdiscetomy: A Cross-Sectional Controlled Study 39 46 EN Nihal Tezel Department of Physical and Rehabilitation Medicine, Health Sciences University Aslı Gençay Can Department of Physical and Rehabilitation Medicine, Faculty of Medicine, Ankara Yıldırım Beyazıt University Original Article 10.18926/AMO/70071 The study aimed to determine the prevalence of kinesiophobia in patients who had undergone lumbar microdiscectomy and to examine its associations with pain intensity, disability, quality of life, depression, anxiety, and satisfaction with surgery. Forty-eight patients with microdiscectomy and 48 healthy controls were enrolled. The Tampa Scale for Kinesiophobia (TSK), Roland-Morris Disability Index (RMDI), Hospital Anxiety and Depression Scale (HADS-A and HADS-D, respectively), and Short Form-36 Health Survey (SF-36) were administered to both groups. The scores of TSK, RMDI, HADS-A, and HADS-D were significantly higher and SF-36 scores were significantly lower in the microdiscectomy than the control group (p<0.001 for all). In the microdiscectomy group, median (min-max) RMDI, HADS-A, and HADS-D scores were 19 (4-34), 10 (0-18), and 9 (0-18), respectively, in kinesiophobic patients, and were significantly higher than 6 (2-20), 3 (0-11), 2.5 (0-11) in non-kinesiophobic patients (all p<0.001). The median (min-max) SF-36 PCS, SF-36 MCS, and VAS scores for surgery satisfaction were 36.5 (8.7-75), 52.1 (11-95), 5, 5 (0-10), respectively, in kinesiophobic patients and were significantly lower than 71 (28-95), 85.5 (9-93), 8.5 (3-10) in non-kinesiophobic patients (all p<0.05). TSK scores were significantly correlated with RMDI, HADS-A, HADS-D, SF-36, and surgery satisfaction scores (all p<0.05). Kinesiophobic patients with lumbar microdiscectomy therefore showed greater disability and psychological morbidity, poorer quality of life, and lower satisfaction with surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 The Preoperative Anterior Pelvic Plane Angle Predicts Cup Anteversion Changes at 1 Year after Total Hip Arthroplasty 31 37 EN Kyota Ishibashi Department of Orthopedic Surgery, Hachinohe City Hospital Hirotaka Oishi Department of Orthopedic Surgery, Hachinohe City Hospital Ryo Araki Department of Orthopedic Surgery, Hachinohe City Hospital Kosuke Kawamura Department of Orthopedic Surgery, Hachinohe City Hospital Isamu Sasaki Department of Orthopedic Surgery, Hachinohe City Hospital Eiji Sasaki Department of Orthopedic Surgery, Hirosaki University Graduate School of Medicine Hikaru Kamada Department of Orthopedic Surgery, Hachinohe City Hospital Masakazu Kogawa Department of Orthopedic Surgery, Hachinohe City Hospital Sunao Tanaka Department of Orthopedic Surgery, Hachinohe City Hospital Takuya Numasawa Department of Orthopedic Surgery, Hachinohe City Hospital Yasuyuki Ishibashi Department of Orthopedic Surgery, Hirosaki University Graduate School of Medicine Original Article 10.18926/AMO/70070 We investigated global alignment changes following total hip arthroplasty (THA) and predictive alignment parameters for increased cup anteversion (CA) by retrospectively analyzing the primary THA data of 75 patients treated at our hospital (49 women, 26 men; age 65.1±5.7 years, BMI 28.3±3.4 kg/m2). Global alignment parameters, i.e., the anterior pelvic plane angle (APPa) and proximal femoral shaft angle (PFSa) and other alignment parameters were measured. CA was evaluated based on the patients’ standing coronal radiographs. ΔCA was defined as the difference in CA from 2 weeks before to 1 year after each THA. We classified the cases as stable (S) (CA < 10°; n=63) and pelvic retroversion (R) (CA ≥ 10°; n=12) groups. Associations between ΔCA and alignment parameters were evaluated by linear regression and a receiver operating characteristic (ROC) analysis. A significant decrease in the PFSa occurred between the 2-week and 1-year post-THA timepoints (7.8±4.3° vs. 4.2±3.6°, p<0.001), with no notable change in other alignment parameters. At 1-year post-THA, the CA of 12 (16%) patients had increased to 4.5±4.4°. Only the preoperative APPa was positively associated with ΔCA (β=0.165, p=0.020). The ROC analysis revealed that the optimal cut-off value for increased CA in the APPa is 2.1° (area under the curve, 0.700; p=0.020; odds ratio, 4.80). The APPa change predicted increased CA, which emphasizes the importance of the use of preoperative standing radiography for identifying the optimal cup positioning for post-THA changes in CA. 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.

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

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

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.<br> 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.<br> 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.

MDPI AG Acta Medica Okayama 2077-0383 15 4 2026 Perioperative Ozoralizumab Management for Patients with Rheumatoid Arthritis Who Underwent Orthopaedic Surgery: A Retrospective Case Series 1422 EN Keiichiro Nishida Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Yoshihisa Nasu Department of Orthopaedic Surgery, Okayama City Hospital Ryozo Harada Department of Orthopaedic Surgery, Kurashiki Sweet Hospital Ryuichi Nakahara Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Masahiro Horita Locomotive Pain Center, Faculty of Medical Development Field, Okayama University Masamitsu Natsumeda Rheumatic Disease Center, Mabi Memorial Hospital Shuichi Naniwa Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Launched in Japan in 2022, ozoralizumab (OZR) is a novel, anti-tumour necrosis factor (TNF)-α inhibitor for treating rheumatoid arthritis (RA) that is refractory to conventional therapies. However, there is a lack of evidence regarding its perioperative management. Methods: This retrospective case series included nine patients with RA who underwent a total of 12 either RA-related (n = 9) or unrelated (n = 3) orthopaedic procedures. We reviewed patient demographics, surgical procedures, perioperative OZR discontinuation periods, and postoperative complications. Results: The mean preoperative OZR discontinuation period was 15.8 days (range, 2–25 days). Sutures were removed at a mean of 12.8 days postoperatively (range, 11–14 days) after adequate wound healing had been confirmed. The mean total discontinuation period was 34.9 days (range, 27–43 days). No cases of surgical site infection (SSI) or delayed wound healing (DWH) were observed during a minimum follow-up period of three months. One patient experienced a disease flare before OZR was restarted. Conclusions: Preoperative OZR discontinuation for up to four weeks appeared to be safe in this cohort. These findings may assist orthopaedic surgeons in determining an appropriate perioperative discontinuation strategy for OZR that minimises SSI and DWH risk while reducing the likelihood of RA flare. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 0031-9317 178 1 2026 Reactive Carbonyl Species Mediate Isothiocyanate Signaling Pathway in Arabidopsis thaliana Guard Cells e70775 EN Sumaiya Farzana Graduate School of Environmental and Life Science, Okayama University Md. Moshiul Islam Graduate School of Environmental and Life Science, Okayama University Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Jun'ichi Mano Science Research Center, Yamaguchi University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Our previous results demonstrated that depletion of glutathione (GSH) rather than elevation of levels of reactive oxygen species (ROS) is highly correlated with the decrease in stomatal aperture induced by isothiocyanates (ITCs), although ROS is considered a key second messenger in stomatal closure, suggesting that another signal component regulates stomatal apertures along with GSH depletion. This study, using Arabidopsis, clarified that reactive carbonyl species (RCS), especially acrolein and 4-hydroxy-(E)-2-nonenal, are determinants of stomatal aperture responses to ITCs. All tested ITCs, allyl isothiocyanate (AITC), sulforaphane (SFN), benzyl isothiocyanate (BITC), and phenethyl isothiocyanate (PEITC), significantly induced stomatal closure, which was inhibited by the RCS scavengers, carnosine and pyridoxamine. The RCS scavengers suppressed ITC-induced depletion of GSH but not elevation of ROS levels. All tested ITCs (AITC, SFN, BITC, and PEITC) increased levels of RCS and non-RCS aldehydes in the epidermal tissues. However, acrolein, 4-hydroxy-(E)-2-nonenal, crotonaldehyde, and (E)-2-pentenal induced stomatal closure at 10 and 100 μM, whereas propionaldehyde, butyraldehyde, and n-pentanal did not at concentrations up to 100 μM. Acrolein and 4-hydroxy-(E)-2-nonenal more effectively induced stomatal closure and GSH depletion than crotonaldehyde and (E)-2-pentenal did. The contents of RCS were more strongly correlated with GSH levels and stomatal closure than with ROS levels. These results suggest that RCS, especially acrolein and 4-hydroxy-(E)-2-nonenal, acts as key regulators of stomatal closure in guard cells in response to ITCs. 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.

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.<br> Objectives: To evaluate the clinical efficacy and safety of endoscopic ultrasound-guided ethanol injection (EUS-EI) and radiofrequency ablation (EUS-RFA) for pNETs.<br> Design: A systematic review and meta-analysis.<br> 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.<br> 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.<br> 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.<br> Trial registration: Not registered. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1349-4147 54 1 2026 Mycobacterium mageritense-associated refractory cutaneous infection and lymphadenitis in an immunocompetent adult: insights from genomic sequencing 19 EN Shinnosuke Fukushima Department of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Jumpei Uchiyama Department of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yoshio Kawakami Department of Dermatology, Okayama University Hospital Yoshiko Matsuura Konohana Dermatology Clinic Satoru Sugihara Department of Dermatology, Okayama University Hospital Shin Morizane Department of Dermatology, Okayama University Hospital Poowadon Muenraya Department of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background Nontuberculous mycobacteria are increasingly recognized as causes of chronic and refractory skin and soft tissue infections, even in individuals without immunodeficiency. Among them, Mycobacterium mageritense is a rare, rapidly growing species that can lead to persistent lesions requiring prolonged antimicrobial therapy. Reports of M. mageritense infections involving both the skin and regional lymph nodes are limited, and this case adds new clinical and genomic insights.<br> Case presentation A 48-year-old previously healthy man presented with a slowly enlarging cutaneous lesion on his lower leg and ipsilateral inguinal lymphadenitis. Empirical antibacterial therapy with β-lactams and macrolides was ineffective. Wound cultures subsequently grew M. mageritense, confirmed by whole-genome sequencing. Several antimicrobial regimens were attempted, and the final successful therapy consisted of oral levofloxacin and minocycline for 4 months, leading to complete clinical resolution. Genomic analysis identified resistance-related genes, including erm(40), aac(2′)-Ib, tet(V), and RbpA, although in vitro minimum inhibitory concentrations showed variable susceptibility. Phylogenetic comparison revealed that the isolate was closely related to previously reported M. mageritense strains from Japan.<br> Conclusions This case demonstrates that M. mageritense can cause cutaneous infection with secondary lymphadenitis in an immunocompetent host. Accurate species identification using molecular or genomic methods and selection of appropriate combination antibiotic therapy based on susceptibility testing are crucial for successful management of such infections. No potential conflict of interest relevant to this article was reported.

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

China Anti-cancer Association Acta Medica Okayama 2095-3941 2026 SPRED2 suppresses the stemness of hepatocellular carcinoma through the p53/miR-506-3p/KLF4 pathway EN Tong Gao Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sachio Ito Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aye Moh-Moh-Aung Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tianyi Wang Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objective: We previously reported that endogenous Sprouty-related, EVH1 domain-containing protein 2 (SPRED2), an inhibitor of the Ras/Raf/ERK-MAPK pathway, controls hepatocellular carcinoma (HCC) cell stemness by downregulating the expression of pluripotency factors, such as Nanog, c-Myc, and KLF4, in an ERK-dependent fashion. However, the exact mechanisms by which SPRED2 regulates HCC cell stemness have not been established.<br> Methods: Three human HCC cell lines [HepG2 (parental and SPRED2-deficient), HLE, and Hep3B] were used. Cells were transfected to downregulate or overexpress proteins. Western blot and RT-qPCR were used to evaluate the level of protein and mRNA expression. Co-immunoprecipitation and ChIP-qPCR were used to examine protein-protein interactions and the activation of gene transcription. Clinical HCC tissues were also used to validate in vitro data.<br> Results: KLF4 was identified as the major pluripotency factor responsible for SPRED2-mediated downregulation of HCC cell stemness and KLF4 expression was regulated by miR-506-3p. SPRED2 formed a protein complex with the tumor suppressor (p53) and upregulated miR-506 gene transcription by binding to the promoter region, resulting in subsequent downregulation of KLF4 mRNA expression. There was a negative correlation between KLF4 expression and miR-506-3p and a positive correlation between miR-506-3p expression and SPRED2 in human HCC samples, highlighting the relevance of the study findings.<br> Conclusions: The current study revealed a novel SPRED2/p53/miR-506-3p/KLF4 axis through which SPRED2 contributes to the suppression of HCC cell stemness and provides a potential new target to prevent HCC progression. 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.<br> Design An open-label, cluster non-randomised controlled trial.<br> 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.<br> 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.<br> 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.<br> 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)).<br> 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.<br> Trial registration number NCT06134518. 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<br> Oral and pharyngolaryngeal papillomas are occasionally detected during esophagogastroduodenoscopy. However, their endoscopic features have not been sufficiently investigated.<br> AIM<br> To distinguish oral and pharyngolaryngeal papillomas from elevated squamous carcinomas, this study examined their endoscopic features.<br> METHODS<br> 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.<br> RESULTS<br> 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%.<br> CONCLUSION<br> 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.

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 49 1 2026 Exploratory Analysis for Development Predictive Models of Immune Checkpoint Inhibitor-Induced Myocarditis Using a Nationwide Claims Database 66 73 EN Reina Yamamoto Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Koki Nakagomi Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Miyu Uchiyama Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Ayana Michihara Department of Pharmacy, Okayama University Hospital Aya F. Ozaki Department of Clinical Pharmacy Practice, School of Pharmacy &amp; Pharmaceutical Sciences, University of California Pranav M. Patel Division of Cardiology, School of Medicine, University of California Maki Tanioka Medical AI Project, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Yoshito Zamami Department of Pharmacy, Okayama University Hospital Takashi Uehara Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Immune checkpoint inhibitors (ICIs), essential in cancer therapy, can cause severe immune-related adverse events (irAEs), including myocarditis with a high fatality rate. Currently, the pathogenesis, biomarkers, and risk factors of ICI-induced myocarditis (ICIM) are not fully understood. This exploratory study aimed to develop machine learning-based models to predict the onset of ICIM within 3 months of starting ICI therapy, using a large health insurance database. The models were constructed using the Light Gradient Boosting Machine (LightGBM) and Random Forest algorithms, incorporating clinical variables such as comorbidities and prior medication classifications. In this study, a strategy combining undersampling and bagging was used to minimize the impact of highly imbalanced datasets. The Random Forest model demonstrated superior performance compared with the LightGBM model, and the SHapley Additive exPlanations (SHAP) analysis for the Random Forest model revealed that the concurrent use of ICIs was the most important variable for predictions. Although predictive performance remains limited (AUROC ≈ 0.63), this exploratory framework demonstrates the feasibility of developing data-driven risk prediction models for ICIM. Future studies with expanded datasets and integration of laboratory parameters are warranted to improve predictive accuracy and potential clinical applicability. No potential conflict of interest relevant to this article was reported.

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

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

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.

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.

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.

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.

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.

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.

岡山医学会 Acta Medica Okayama 0030-1558 137 3 2025 令和６年度岡山医学会賞　胸部・循環研究奨励賞（砂田賞） 95 97 EN Shinichi Kawana Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 137 3 2025 令和６年度岡山医学会賞　がん研究奨励賞（林原賞・山田賞） 89 91 EN Shota Takihira Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0007-8506 74 1 2025 Improvement of anodic oxide film characteristics of Al-Cu alloy by refinement of IMCs with large-area electron beam irradiation 263 267 EN T. Shinonaga Faculty of Environmental, Life, Natural Science & Technology, Okayama University A. Sebe Graduate School of Environmental, Life, Natural Science & Technology, Okayama University M. Taniguchi Shimano Research Laboratories, R&D Strategy Dept., SHIMANO INC. T. Fujii Shimano Research Laboratories, R&D Strategy Dept., SHIMANO INC. A. Okada Faculty of Environmental, Life, Natural Science & Technology, Okayama University Al-Cu alloy has been widely applied to automobile products due to its light weight and high strength, but pitting corrosion easily occurs due to intermetallic compounds (IMCs) in Al-Cu alloy. Anodizing process has been conventionally performed to improve the corrosion resistance of Al-Cu alloy surface. However, IMCs in Al-Cu alloy lead to defects in anodic oxide film. In this study, refinement of IMCs in Al-Cu alloy surface by large-area EB irradiation was proposed. Experimental results show that reflectance and corrosion resistance of anodic oxide film formed on Al-Cu alloy surface are improved by refinement of IMCs with the EB irradiation. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2059-7029 10 11 2025 Association between adjuvant chemotherapy and outcomes in resected locoregional recurrence of hormone receptor-positive HER2-negative breast cancer: a multi-institutional retrospective study 105889 EN Y. Ozaki Department of Breast Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research E. Tokuda Department of Medical Oncology, Fukushima Medical University Y. Sagara Department of Breast Surgery, Social Medical Corporation Hakuaikai Sagara Hospital F. Hara Department of Breast Oncology, Aichi Cancer Center Hospital S. Sasada Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University M. Sawaki Department of Breast Oncology, Aichi Cancer Center Hospital C. Kanbayashi Department of Breast Oncology, Niigata Cancer Center Hospital T. Yamanaka Department of Breast Surgery and Oncology, Kanagawa Cancer Center T. Onishi Department of Breast Oncology, National Cancer Center Hospital East Y. Fujiki Department of Breast Surgery, Social Medical Corporation Hakuaikai Sagara Hospital A. Suto Department of Breast Oncology, National Cancer Center Hospital Y. Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital E. Tokunaga Department of Breast Oncology, National Hospital Organization Kyushu Cancer Center T. Aruga Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital R. Nakamura Division of Breast Surgery, Chiba Cancer Center T. Fujisawa Department of Breast Oncology, Gunma Prefectural Cancer Center S. Saji Department of Medical Oncology, Fukushima Medical University H. Iwata Department of Advanced Clinical Research and Development, Nagoya City University T. Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Background: To evaluate the association of adjuvant chemotherapy and prognosis for locoregional recurrence (LRR) in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative subtype breast cancer.<br> Patients and methods: We carried out a multi-institutional retrospective cohort study in patients with breast cancer who developed HR-positive HER2-negative LRR. Patients who underwent curative surgery for LRR between 2014 and 2018 were categorized based on whether they received adjuvant chemotherapy for LRR (CTx versus no-CTx). Invasive disease-free survival (iDFS) was evaluated between the groups by Cox proportional hazards analysis. The primary analysis used a double-robust Cox model incorporating inverse probability of treatment weighting, and a sensitivity analysis using propensity score matching was also carried out.<br> Results: A total of 958 patients were included. The median time from the primary surgery to LRR diagnosis was 9.5 years (interquartile range 3.1-10.1 years). There were 235 patients (25%) in the CTx group and 722 (75%) in the no-CTx group. Among all patients, the 5-year iDFS rate was 75.4% [95% confidence interval (CI) 72.4% to 78.2%]. Multivariate analysis showed better iDFS in the CTx group (hazard ratio 0.70, 95% CI 0.49-0.99, P = 0.045). Sensitivity analysis supported these findings. Subgroup analyses showed that the CTx group had better iDFS in cases with non-ipsilateral breast tumor recurrence (IBTR), recurrences during adjuvant endocrine therapy for primary breast cancer, and without perioperative chemotherapy for primary breast cancer. Secondary analysis showed no significant difference with a worse trend toward overall survival in the CTx group with multivariate Cox proportional hazards analysis.<br> Conclusion: Adjuvant chemotherapy for HR-positive HER2-negative LRR was associated with better iDFS, particularly in cases of non-IBTR, recurrences during adjuvant endocrine therapy, and no prior perioperative chemotherapy for their primary tumor. However, the retrospective design and inability to distinguish true recurrences from new primary tumors in IBTR warrant cautious interpretation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0718-9508 2025 Suppression of Na+ Uptake Via Apoplastic Flow by Chitosan in Rice EN Maoxiang Zhao Graduate School of Environmental and Life Science, Okayama University Md. Asadulla Al Galib Graduate School of Environmental and Life Science, Okayama University Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Yoshihiko Hirai Graduate School of Environmental and Life Science, Okayama University Yoshitaka Nakashima Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Izumi C. Mori Institute of Plant Science and Resources, Okayama University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Purpose: Chitosan enhances tolerance to salinity in rice. Apoplastic flow plays a crucial role in the accumulation of sodium (Na+) in rice under salinity. This study investigated the effects of exogenous chitosan on apoplastic flow and Na+ uptake in NaCl-treated rice seedlings. Methods: We employed an apoplastic tracer, trisodium salt of 8-hydroxy-1,3,6-pyrenetrisulphonic acid (PTS), in order to evaluate apoplastic flow in rice (Oryza sativa L., cv. Nipponbare) seedlings that were hydroponically grown in the solution containing NaCl (0 and 25 mM), and chitosan (0 mg L− 1, 10 mg L− 1, and 50 mg L− 1). Results: Application of 25 mM NaCl significantly increased PTS uptake and Na+ content in shoots but did not affect K+ content, resulting in a lower K+/Na+ ratio although 25 mM NaCl did not affect the seedling growth. The application of chitosan suppressed Na+-enhanced PTS uptake and Na+ accumulation in shoots without affecting the K+ content, which led to a higher K+/Na+ ratio. Moreover, chitosan did not affect the reducing sugar content or electrical conductivity in the solution containing NaCl. Conclusions: These results suggest that application of chitosan suppressed Na+-enhanced apoplastic flow to reduce Na+ uptake in rice seedlings. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 1347-9032 2025 Genomic Profiling of Pediatric Solid Tumors With a Dual DNA/RNA Panel: JCCG-TOP2 Study EN Kayoko Tao Department of Pediatrics, National Cancer Center Hospital Takako Yoshioka Department of Pathology, National Center for Child Health and Development Miho Kato Department of Childhood Cancer Data Management, National Center for Child Health and Development Kazuyuki Komatsu Department of Pediatrics, Hamamatsu University School of Medicine Shinichi Tsujimoto Department of Pediatrics, Yokohama City University Kenichi Sakamoto Department of Pediatrics, Shinshu University School of Medicine Kazuki Tanimura Department of Pediatrics, National Cancer Center Hospital Minako Sugiyama Department of Pediatrics, National Cancer Center Hospital Masahiro Sekiguchi Department of Pediatrics, The University of Tokyo Yoshiko Nakano Department of Pediatrics, The University of Tokyo Yoshihiro Otani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasushi Yatabe Department of Diagnostic Pathology, National Cancer Center Hospital Akihiko Yoshida Department of Diagnostic Pathology, National Cancer Center Hospital Hajime Okita Department of Pathology, Keio University School of Medicine Junko Hirato Department of Pathology, Public Tomioka General Hospital Kenichi Kohashi Department of Pathology, Graduate School of Medicine, Osaka Metropolitan University Yukichi Tanaka Department of Pathology, Kanagawa Children's Medical Center Shinji Kohsaka Division of Cellular Signaling, National Cancer Center Research Institute Takashi Kubo Department of Clinical Genomics, National Cancer Center Research Institute Kuniko Sunami Department of Laboratory Medicine, National Cancer Center Hospital Makoto Hirata Department of Genetic Medicine and Services, National Cancer Center Hospital Shuichi Tsutsumi Genome Science & Medicine Division, Research Center of Advanced Science and Technology, The University of Tokyo Hiroyuki Aburatani Genome Science & Medicine Division, Research Center of Advanced Science and Technology, The University of Tokyo Katsuyoshi Koh Department of Hematology and Oncology, Saitama Children's Medical Center Masahiro Hirayama Department of Pediatrics, Mie University Graduate School of Medicine Shuhei Karakawa Department of Pediatrics, Hiroshima University Hospital Yukayo Terashita Department of Pediatrics, Hokkaido University Hospital Hiroyuki Fujisaki Department of Pediatric Hematology and Oncology, Osaka City General Hospital Takeshi Yagi Okinawa Prefectural Nanbu Medical Center & Children's Medical Center Akihiro Yoneda Department of Pediatric Surgery, National Center for Child Health and Development Shinji Mochizuki Department of Pediatrics, National Center for Global Health and Medicine, Japan Institute for Health Security Hiroyuki Shichino Department of Pediatrics, National Center for Global Health and Medicine, Japan Institute for Health Security Tatsuya Suzuki Department of Hematology, National Cancer Center Hospital Tetsuya Takimoto Department of Childhood Cancer Data Management, National Center for Child Health and Development Koichi Ichimura Department of Pathology, Kyorin University Faculty of Medicine Chitose Ogawa Department of Pediatrics, National Cancer Center Hospital Kimikazu Matsumoto Children's Cancer Center National Center for Child Health and Development Hitoshi Ichikawa Department of Clinical Genomics, National Cancer Center Research Institute Motohiro Kato Department of Pediatrics, The University of Tokyo To develop an optimized genomic medicine platform for pediatric cancers, a nationwide cancer genome profiling project was conducted from January 2022 to February 2023 in collaboration with the Japan Children's Cancer Group. This prospective observational study analyzed matched blood and FFPE tumor samples from patients aged 0–29 years with solid tumors. Genomic analysis used the TOP2 hybrid capture–enrichment system, targeting 737 and 455 genes in the DNA and RNA panels, along with allele-specific genome copy number alterations. A total of 210 patients from 50 institutions were enrolled across Japan (median age, 8 years; range, 0–25). Of these, 154 (77%) were enrolled at diagnosis or during/after initial treatment and 56 (27%) at disease progression or relapse. The TOP2 findings had great benefits in clarifying the diagnosis of pediatric solid tumors. Among the 204 patients with genomic results, 147 (72%) had potentially actionable findings, including diagnostic, prognostic, and therapeutic findings in 111 (54%), 61 (30%), and 64 (31%), respectively. Oncogenic fusions were noted in 45 (23%) patients. A copy number alteration was identified in at least one genomic region in 170 (83%) patients. Two patients exhibited a high tumor mutation burden. Seventeen (8%) patients harbored a germline pathogenic/likely pathogenic variant in cancer-predisposing genes. This study highlighted the feasibility of implementing a nationwide precision medicine platform and the clinical utility of the TOP2 system for pediatric cancers. The results support the integration of genomic data into the standard clinical care of pediatric patients with cancer, both at diagnosis and at relapse. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 0006-2928 2025 German Chamomile (Matricaria chamomilla) Induces Cytochrome P450 Expression Through Increased BMAL1 Protein Expression in Liver Nuclei EN Moka Ikeda Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University Yuya Tsurudome Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University Mai Enrin Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University Yukiyo Wada Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University Michiko Horiguchi Department of Regenerative and Therapeutic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kentaro Ushijima Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University German chamomile (Matricaria chamomilla) is a medicinal herb that promotes improved digestion and reduces insomnia. Although it is widely used worldwide, the mechanism of induction of drug-metabolizing enzymes is unknown. We found that German chamomile extracts induced cytochrome P450 expression at the transcriptional stage. Cyp3a11 expression is decreased at night in wild-type mice, but German chamomile extract induced nocturnal Cyp3a11 and Cyp1a2 expression. German chamomile extract increased the nuclear protein expression of the clock gene BMAL1, which drives and abolishes the rhythm of Cyp3a11 expression. By contrast, German chamomile extract did not significantly alter clock gene expression in the suprachiasmatic nucleus (SCN). Similarly, it did not affect the mRNA expression of the clock genes in the kidneys. Because it did not induce the mRNA expression of ATP-binding cassette (ABC) transporters (Abcb1a, Abcc2, Abcc4, and Abcg2) in the kidney, German chamomile extract had no effect on the transcription of pharmacokinetics-related molecules other than CYPs. German chamomile extract promoted liver-selective nuclear transfer rhythm changes in clock genes and induced the expression of CYPs. This study may help to explain the mechanism of drug interactions associated with chronic German chamomile extract consumption. No potential conflict of interest relevant to this article was reported.

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

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

Wiley Acta Medica Okayama 2328-9503 2025 Dorsolateral Cervical Cord T2 Hyperintensity in KIF1C-Related Disease (Spastic Paraplegia 58): Two Long-Duration Cases EN Akihiko Mitsutake Department of Neurology, Graduate School of Medicine, The University of Tokyo Masao Osaki Department of Neurology, Graduate School of Medicine, The University of Tokyo Takashi Matsukawa Department of Neurology, Graduate School of Medicine, The University of Tokyo Miho Osako Department of Neurology, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled Chisen Takeuchi Department of Neurology, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Jun Mitsui Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Ryo Kurokawa Department of Radiology, Graduate School of Medicine, The University of Tokyo Harushi Mori Department of Radiology, School of Medicine, Jichi Medical University Yuji Takahashi Department of Neurology, Graduate School of Medicine, The University of Tokyo Jun Goto Department of Neurology, Graduate School of Medicine, The University of Tokyo Shoji Tsuji Institute of Medical Genomics, International University of Health and Welfare Tatsushi Toda Department of Neurology, Graduate School of Medicine, The University of Tokyo Pathogenic variants in KIF1C cause Spastic Paraplegia 58 (SPG58), typically presenting with cerebellar ataxia and spastic paraparesis. We report two unrelated patients with spastic paraparesis, cerebellar ataxia, and tremor. Whole-exome sequence analysis identified novel homozygous variants in the motor domain of KIF1C (NM_006612.6): c.921G>A (p.Trp307Ter) and c.607C>T (p.Arg203Trp). In addition to the canonical brain MRI showing leukoencephalopathy with posterior dominance and hyperintensity along the corticospinal tracts, both patients showed symmetric T2 hyperintensity confined to the lateral and dorsal columns of the cervical cord. Given the long disease durations (22 and 51 years), these findings may represent late-emerging or previously overlooked spinal cord involvement and broaden the neuroradiological spectrum of SPG58. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0169-555X 493 2026 Coast uplifted by nearby shore-parallel active submarine faults during the 2024 Mw 7.5 Noto Peninsula earthquake 110069 EN Hideaki Goto Hiroshima University Tomoru Yamanaka Natural History Museum and Institute Chiba Tomohiro Makita Hiroshima University Yoshiya Iwasa University of Teacher Education Fukuoka Takuro Ogura Hyogo University of Teacher Education Kyoko Kagohara Yamaguchi University Yasuhiro Kumahara Hiroshima University Yasuhiro Suzuki Nagoya University Nobuhisa Matta Okayama University Tatsuto Aoki Kanazawa University Wataru Mori Hiroshima University Kenta Haranishi Hiroshima University Takashi Nakata Hiroshima University An Mw 7.5 earthquake occurred at 16:10 JST on January 1, 2024 at a depth of 16 km on the Noto Peninsula, central Japan. This earthquake was the second-largest intraplate earthquake recorded in Japan during 120 years of seismic observation, and it caused approximately 100 km of coastal seafloor emergence along the peninsula's northern coast. Herein, we mapped the emergence of this coastal seafloor and measured the uplift along the coast. The movement of the coastline led to the emergence of approximately 4.4 km2 of seafloor, which is continuous and probably the longest in the world. We determined the uplift distribution along the coast using the white remains of a reddish seaweed called Corallina pilulifera. Its upper limit exhibited a distinct horizontal line, effectively representing the uplift amount throughout the peninsula. Two large, uplifted regions were identified, around Cape Saruyama (5.21 m) in the west and Cape Kurasaki (2.70 m) in the north. Although active offshore submarine faults have been extensively researched, the fault traces remain poorly defined because they are primarily interpreted from seismic reflection profiles. We identified the distribution of active submarine faults using anaglyph-type stereoscopic images, confirming the subsurface deformation structure seen through the seismic reflection profiles. The main fault trace is primarily straight and contiguous with the nearby north coast. The uplift amount is greater near the active fault traces on the north side and diminishes sharply with increasing distance from these faults, indicating a southward tilt of surface uplift related to the active submarine faults. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Ileus Tube-Related Intussusception: A Case Report and Review of 80 Previously Reported Cases 469 474 EN Teruyuki Tsujii Department of Surgery, Matsuda Hospital Tatsuo Matsuda Department of Surgery, Matsuda Hospital Yuji Kimura Department of Surgery, Matsuda Hospital Ryoichi Katsube Department of Surgery, Matsuda Hospital Hironori Iwadou Department of Surgery, Matsuda Hospital Sadami Funabiki Department of Surgery, Matsuda Hospital Yasuaki Kamikawa Department of Surgery, Matsuda Hospital Tadakazu Matsuda Department of Surgery, Matsuda Hospital Case Report 10.18926/AMO/69851 We report a rare case of ileus tube-related intussusception in an adult. A 56-year-old man with adhesive bowel obstruction was treated with a nasointestinal ileus tube. Although his condition initially improved, persistent abdominal pain led to the diagnosis of intussusception via CT imaging. Manual repositioning of the tube resolved the intussusception without the need for bowel resection. A review of 80 previously reported cases of ileus tube-associated intussusception (total 81 cases, 95 lesions) highlighted the timing of onset, treatment strategies, and precautions. Early detection and diagnosis are crucial to prevent severe complications and preserve bowel function. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Exacerbation of Proteinuria in a Patient with Behçet’s Disease and IgA Nephropathy Following Colchicine Discontinuation 457 461 EN Tomohiko Asakawa Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yu Katayama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yoshimasa Sakurabu Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Katsuyoshi Katayama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Onishi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Natsumi Matsuoka-Uchiyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hidemi Takeuchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Keiko Tanaka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Ryoko Umebayashi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Rika Takemoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/69849 This case involves a 23-year-old male who was diagnosed with Behçet’s disease 5 years ago and managed with colchicine. Two months ago, he underwent renal biopsy due to abnormal urinalysis and kidney dysfunction, leading to a diagnosis of IgA nephropathy. He subsequently underwent tonsillectomy followed by glucocorticoid pulse therapy. However, after the tonsillectomy, discontinuing colchicine led to increased proteinuria, despite the glucocorticoid pulse therapy. Upon reintroducing colchicine, urinary protein excretion decreased, achieving incomplete remission. These findings suggest that colchicine may be effective in decreasing proteinuria in patients with Behçet’s disease complicated by IgA nephropathy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Recurrence of FVIII Inhibitor during Surgery in a Patient with Severe Hemophilia A Receiving Emicizumab Prophylaxis 451 455 EN Moe Hagihara Department of Hematology and Oncology, Okayama University Hospital Keisuke Seike Department of Hematology and Oncology, Okayama University Hospital Kenta Hayashino Department of Hematology and Oncology, Okayama University Hospital Takao Yasuhara Department of Neurological Surgery, Okayama University Hospital Kyohei Kin Department of Neurological Surgery, Okayama University Hospital Yuichi Hirata Department of Neurological Surgery, Okayama University Hospital Hiroki Kobayashi Department of Hematology and Oncology, Okayama University Hospital Wataru Kitamura Department of Hematology and Oncology, Okayama University Hospital Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Division of Transfusion and Cell Therapy, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Case Report 10.18926/AMO/69848 Emicizumab, a bispecific monoclonal antibody, benefits patients with severe hemophilia A. It alters laboratory assessments of coagulation activity, requiring anti-idiotype monoclonal antibodies for accurate monitoring. A 64-year-old man, receiving emicizumab regularly, was admitted for laminoplasty. We planned to use FVIII replacement during the perioperative period after confirming the disappearance of inhibitors, monitoring coagulation activity with anti-idiotype monoclonal antibodies. Activated partial thromboplastin time was prolonged on postoperative day 2, prompting an immediate switch to eptacog alfa. The patient recovered without bleeding. This case underscores the necessity of anti-idiotype monoclonal antibodies for accurate monitoring. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Perioperative Team Management Was Beneficially Associated with Prolonged Postoperative Hospital Stays after Long Lower-Abdominal Surgeries 445 449 EN Junya Matsumi Department of Anesthesiology and Intensive Care Medicine, National Cancer Center Hospital Original Article 10.18926/AMO/69847 Our hospital began a PERIO program (perioperative patient management by a multi-disciplinary team from multiple departments) in 2016 to improve patient outcomes. We retrospectively analyzed the clinical effects of the PERIO program regarding the postoperative hospital stay (PHS) in the patients aged ≥ 18 years who underwent long lower-abdominal surgery at our hospital during the period April 2019 to March 2023. We excluded the cases of patients whose general anesthesia use was < 8 h, those for whom another surgery was performed simultaneously at another site, and emergency surgeries. The outcome was prolonged PHS, defined as exceeding the scheduled number of days specified in the patient’s clinical pathway. Among the 480 patients, prolonged PHS was observed for 270 patients (56.3%). In a multivariate logistic regression using advanced age, sex, high-risk general state, surgery requiring colon resection, serious adverse events (SAEs), and PERIO use, the following were associated with prolonged PHS: advance age (odds ratio [OR] 4.91, 95% confidence interval [CI]: 2.68-8.99, p=0.01), surgery requiring colon resection (OR 4.91, 95%CI: 2.68-8.99, p<0.001), SAE (OR 18.7, 95%CI: 7.22-48.2, p<0.001), and PERIO (OR 0.25, 95%CI: 0.13-0.47, p<0.001). The use of the PERIO program was thus beneficially associated with PHS after long lower-abdominal surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Frailty at 1 Month before ICU Admission Poses a Hospital Mortality Risk in Cancer Survivors whose Condition Has Deteriorated due to Medical Factors 437 444 EN Junya Matsumi Department of Anesthesiology and Intensive Care Medicine, National Cancer Center Hospital Tetsufumi Sato Department of Anesthesiology and Intensive Care Medicine, National Cancer Center Hospital Original Article 10.18926/AMO/69846 The optimal indications for intensive care unit (ICU) treatment for critically ill cancer survivors whose condition has deteriorated due to medical factors are unclear. To test our hypothesis that frailty before deterioration was associated with hospital mortality in this patient population, we retrospective analyzed the cases of the patients admitted to the ICU at the National Cancer Center Hospital, Japan (April 2014-March 2022). We excluded patients who underwent surgery within 28 days or were denied critical care within 24 h or admitted after cardiopulmonary arrest. Their Clinical Frailty Scale (CFS) scores at 1 month before ICU admission (Pre-ICU) were obtained. Frailty was defined as CFS scores ≥4 points. We analyzed 298 admissions and observed that the mortality rate at hospital discharge was significantly higher in the frailty group (n=119). A multivariate analysis demonstrated that the following factors were significantly associated with hospital mortality: Pre-ICU frailty (OR 2.00, 95%CI: 1.19-3.36, p=0.009), cancer type (hematological: OR 2.93, 95%CI: 1.42-6.05, p=0.004), and Sequential Organ Failure Assessment score at ICU admission (OR 0.88, 95%CI: 0.82-0.95, p=0.0008). Frailty retrospectively assessed using the CFS at 1 month pre-ICU admission is a risk factor for hospital mortality in these cancer survivors. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Association of Weekend Admission and In-Hospital Mortality in Adult Patients with Acute Myeloid Leukemia in Japan 431 436 EN Takahiro Inoue Healthcare Management Research Center, Chiba University Hospital Hiroyo Kuwabara Healthcare Management Research Center, Chiba University Hospital Koh Yamamoto Department of Hematology, Yokohama City Minato Red Cross Hospital Original Article 10.18926/AMO/69845 The effect of weekend admission on patient mortality has been investigated in several therapeutic areas, including acute myeloid leukemia (AML), but the investigations’ results are controversial. We evaluated the relationship between in-hospital mortality and weekend admission in adult patients with AML in Japan by conducting a retrospective observational study using administrative data from 144 acute care hospitals from which patients were discharged between April 2014 and March 2019. The primary endpoint was in-hospital mortality, compared between weekend and weekday admissions. Among the 1,340 eligible patients, 11% (150) were admitted during a weekend. The in-hospital mortality rates of the patients admitted during weekends and those admitted on a weekday were 28% (42/150) and 17% (204/1190), respectively. After an adjustment for covariates, weekend admission was associated with a significantly higher risk of in-hospital mortality than weekday admission (HR 1.70, 95%CI: 1.20-2.40; p=0.003). However, such an association was not observed in patients treated in a bio-clean room (HR 1.26, 95%CI: 0.65-2.42). Our results demonstrate that for patients with AML, weekend admission was independently associated with a higher risk of death during hospitalization. An appropriate system is necessary for these patients. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 COVID-19 and the Risks of Migraine and Headache: A Mendelian Randomization Study 413 419 EN Zhiyun Jiang Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University Ying Xi Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University Original Article 10.18926/AMO/69843 Several observational studies suggested that migraine headache attacks were associated with coronavirus disease 2019 (COVID-19). We investigated genetic causal links between COVID-19 phenotypes and the development of headache and migraine, including migraine with aura (MA) and migraine without aura (MO). We conducted a two-sample Mendelian randomization (MR) analysis to estimate the genetic association in European populations. The inverse-variance weighted (IVW) method was used as the main approach in the MR analyses, together with weighted median and MR-Egger methods. We also performed a series of sensitivity tests to assess the robustness of the MR results. The MR results demonstrated that COVID-19 severity, hospitalization, and susceptibility had no causal effect on the risks of headache, migraine, MA, or MO. No horizontal pleiotropy was detected, and the results were robust as supported by the sensitivity analysis findings. Our analyses identified no casual effect of COVID-19 severity, hospitalization, or susceptibility on the risks of headache or migraine in European populations. No potential conflict of interest relevant to this article was reported.

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

Frontiers Media SA Acta Medica Okayama 1662-453X 19 2025 Effects of visual spatial frequency on audiovisual interaction: an event-related potential study 1599114 EN Fengxia Wu School of Artificial Intelligence, Changchun University of Science and Technology Yanna Ren Department of Psychology, College of Humanities and Management, Guizhou University of Traditional Chinese Medicine Tengfei Hao School of Artificial Intelligence, Changchun University of Science and Technology Jingjing Yang School of Artificial Intelligence, Changchun University of Science and Technology Qiong Wu Department of Psychology, Suzhou University of Science and Technology Jiajia Yang Cognitive Neuroscience Laboratory, Graduate School of Natural Science and Technology, Okayama University Meng Wang School of Artificial Intelligence, Changchun University of Science and Technology Spatial frequency is a fundamental characteristic of visual signals that modulates the audiovisual integration behavior, but the neural mechanisms underlying spatial frequency are not well established. In the present study, the high temporal resolution of event-related potentials was used to investigate how visual spatial frequency modulates audiovisual integration. A visual orientation discrimination task was used, and the spatial frequency of visual stimuli was manipulated under three conditions. Results showed that the influence of visual spatial frequency on audiovisual integration is a dynamic process. The earliest audiovisual integration occurred over the left temporal-occipital regions in the early sensory stage (60–90 ms) for high spatial frequency conditions but was absent for low and middle spatial frequency conditions. In addition, audiovisual integration over fronto-central regions was delayed as spatial frequency increased (from 230–260 ms to 260–320 ms). The integration effect was also observed over parietal and occipital regions at 350–380 ms, and its strength gradually decreased at higher spatial frequencies. These discrepancies in the temporal and spatial distributions of audiovisual integration imply that the role of spatial frequency varies between early sensory and late cognitive stages. The findings of this study offer the first neural demonstration that spatial frequency modulates audiovisual integration, thus providing a basis for studying complex multisensory integration, especially in semantic and emotional domains. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2189-7948 26 4 2025 Video review by utilizing asynchronous video communication platform 375 378 EN Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eiko Mitsuda Kato & Namiki-dori Hospital Yukichika Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Kato Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mano Soshi BonBon, Inc Masaya Higuchi Harvard Medical School Mikako Obika 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 Tadayuki Hashimoto Department of Emergency Medicine, Brigham and Women's Hospital Background: Video review is widely recognized as an effective method for teaching communication; however, it can increase educators' workload and learners' stress.<br> Methods: We utilized Tsucom, an online platform developed by BonBon, Inc., which enables asynchronous video communication instead of traditional styles. An 11-min and 42-s consultation video from a fifth-year resident was uploaded, and 10 physicians provided 30 text-based feedback.<br> Results: In this pilot survey, the utility and ease of use were rated 4.4 and 4.1 out of 5, respectively.<br> Conclusions: While asynchronous online video reviews provided flexibility and greater participation, challenges remain, and further trials and evaluations were deemed necessary. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0031-9317 177 4 2025 Comparative Transcriptome Reveals ART1-Dependent Regulatory Pathways for Fe Toxicity Response in Rice Roots e70398 EN Yoshiaki Ueda Crop, Livestock and Environment Division, Japan International Research Center for Agricultural Sciences Naoki Yamaji Institute of Plant Science and Resources, Okayama University Matthias Wissuwa Crop, Livestock and Environment Division, Japan International Research Center for Agricultural Sciences Iron (Fe) is an essential element for plants, but an excess supply can have detrimental effects. Fe toxicity induces complex physiological and genetic responses, and due to this complexity, the knowledge of transcriptional regulatory mechanisms under Fe toxicity is very limited. Previous studies suggested that plant responses to excess Fe involve oxidative stress caused by reactive oxygen species (ROS), which itself causes transcriptional changes. We hypothesized that dissecting these complex responses could lead to the identification of a novel factor and conducted a comparative transcriptome analysis using roots of rice plants exposed to nutrient solutions containing 1 or 5 mM of hydrogen peroxide (a major form of ROS) or 300 mg L−1 of Fe (as FeSO4). Genes induced by hydrogen peroxide overlapped with 62%, 49%, and 30% of Fe toxicity-upregulated genes at 3 h, 1 day, and 3 days following treatment initiation. Subsequent gene co-expression analyses classified genes into 21 groups with varying responsiveness to ROS and Fe toxicity. Genes in group 15 were specifically upregulated by Fe toxicity and overlapped significantly with aluminum (Al)-inducible genes and target genes of the Zn-finger transcription factor, ART1, which regulates Al response in rice roots. Additional experiments using the art1 knock-out mutant demonstrated that ART1 is crucial for upregulating genes such as STAR2 and FRDL4 in response to Fe toxicity. This study reveals the contribution of ART1-dependent regulatory pathways in rice roots under Fe toxicity. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0361-5995 89 3 2025 Autoclaved lightweight aerated concrete suppressed N2O and CO2 emissions from paddy soil e70091 EN Nagoda R. R. W. S. Rathnayake Department of Soil Science, Faculty of Agriculture, University of Ruhuna Morihiro Maeda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Dewpura A. L. Leelamanie Department of Soil Science, Faculty of Agriculture, University of Ruhuna Atsushi Yatagai Clion Co. Ltd Autoclaved lightweight aerated concrete (AAC), a construction waste that is utilized as a soil amendment, can influence terrestrial carbon dioxide (CO2) emissions. Still, no evidence exists regarding its impact on the emission of nitrous oxide (N2O), which has a higher global warming potential. This study examined effects of AAC on CO2 and N2O emissions from paddy soil under compacted and non-compacted conditions, under 60% and 100% water-holding capacity (WHC). Samples were incubated in glass vials (25°C) for 21 days. Emissions of CO2 and N2O were measured on days 0, 1, 3, 7, 14, and 21 using gas chromatography. The results revealed that AAC significantly (p < 0.05) lowered N2O emission rate during the whole period of incubation, while it suppressed CO2 emission rate only at the early stages (∼7 days) of incubation. In compacted soil, the emissions of CO2 were significantly lower, while N2O was significantly higher than that in non-compacted soil, showing the influence of soil physical conditions. The emissions of CO2 and N2O were significantly lower at 100% WHC than those at 60% WHC. AAC suppressed both CO2 and N2O emissions under both compaction and WHC levels. The results confirm that AAC supports suppressing terrestrial emission of both CO2 and N2O, indicating that AAC has a potential as a sustainable soil amendment that enhances the climate change resilience. No potential conflict of interest relevant to this article was reported.

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

American Chemical Society (ACS) Acta Medica Okayama 2574-0962 2025 Enhanced Charge-Transfer Kinetics Enabled by ZrO2–Based Dielectric Layers in Lithium-Ion Batteries EN Takashi Teranishi Graduate School of Natural Science and Technology, Okayama University Yusuke Higaki Graduate School of Natural Science and Technology, Okayama University Tomonori Imamura Graduate School of Natural Science and Technology, Okayama University Motoki Horibe Department of Advanced Ceramics, Nagoya Institute of Technology Shinya Kondo Department of Energy Engineering, Nagoya University Chinatsu Sasaoka R&D Laboratory, Nippon Denko Co., Ltd. Hikaru Hirabaru R&D Laboratory, Nippon Denko Co., Ltd. Shingo Katayama R&D Laboratory, Nippon Denko Co., Ltd. Masanobu Nakayama Department of Advanced Ceramics, Nagoya Institute of Technology Akira Kishimoto Graduate School of Natural Science and Technology, Okayama University The development of high-rate capability lithium-ion batteries (LIBs) requires suppression of charge-transfer resistance (RCT) at electrode–electrolyte interfaces. Here, zirconia-based dielectric oxides (MZ; M = Y, Gd, Sm, Er, etc.) were introduced onto LiCoO2 (LCO) surfaces as electronically and ionically insulating modifiers to accelerate interfacial ion transport. Electrochemical impedance spectroscopy showed that Y2O3 modified ZrO2 (YZ) decoration reduced RCT from 75.8 Ω in reference LCO to 38.3 Ω, accompanied by a 2.3-fold improvement in capacity retention at 20C. Density functional theory molecular dynamics (DFT–MD) simulations showed that solvated Li ions coordinate with surface oxygen atoms in discharging, and that adsorption energies are governed by local charge distributions determined by stabilizing cations. Optimal adsorption activity, and thus the lowest RCT, occurred when the surface charge corrugation was balanced. These findings provide design principles for dielectric interface engineering to enhance rate capability of LIBs. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2504-3129 6 4 2025 Drip Fertigation in Greenhouse Eggplant Cultivation: Reducing N2O Emissions and Nitrate Leaching 116 EN Wataru Shiraishi Kochi Prefectural Agricultural Research Center Shion Nishimura Department of Bioresource Production Science, United Graduate School of Agriculture, Ehime University Morihiro Maeda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hideto Ueno Department of Bioresource Production Science, United Graduate School of Agriculture, Ehime University Drip fertigation (DF) is a sustainable agricultural management technique that optimizes water and nutrient usage, enhances crop productivity, and reduces environmental impact. Herein, we compared the effects of DF and conventional fertilization (CF) with a basal fertilizer on yield, soil inorganic nitrogen dynamics, N2O emissions, and nitrogen leaching during facility-grown eggplant cultivation. The experiment was conducted in a greenhouse from September 2023 to May 2024, with treatments arranged in three rows and three replicates. Soil, gas, and water samples were collected and analyzed throughout the growing season. The results revealed that the DF treatment produced yields comparable to those obtained with the CF treatment while significantly reducing nitrogen and phosphorus inputs. DF effectively prevented excessive nitrogen accumulation in the soil and reduced nitrogen loss through leaching and gas emissions. N2O emissions were significantly lower by more than 60% under DF than under CF. Precise nutrient management in DF suppressed nitrification and denitrification processes, mitigating N2O emissions. DF also significantly reduced nitrogen leaching by more than 70% compared with that in CF. These findings demonstrate that DF effectively enhances agricultural sustainability by improving nutrient use efficiency, reducing greenhouse gas emissions, and minimizing nitrogen leaching during the cultivation of facility-grown eggplant. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2041-1723 16 1 2025 Efficient and stable n-type sulfide overall water splitting with separated hydrogen production 8786 EN Haolin Luo Research Center for Combustion and Environment Technology, Shanghai Jiao Tong University Zhixi Liu Research Center for Combustion and Environment Technology, Shanghai Jiao Tong University Haifeng Lv State Key Laboratory of Precision and Intelligent Chemistry, School of Chemistry and Material Sciences, and Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), University of Science and Technology of China Junie Jhon M. Vequizo Institute of Aqua Regeneration, Shinshu University Mengting Zheng College of Chemical and Biological Engineering, Zhejiang University Feng Han Research Center for Combustion and Environment Technology, Shanghai Jiao Tong University Zhen Ye Research Center for Combustion and Environment Technology, Shanghai Jiao Tong University Akira Yamakata Faculty of Natural Science and Technology, Okayama University Wenfeng Shangguan Research Center for Combustion and Environment Technology, Shanghai Jiao Tong University Adam F. Lee Centre for Catalysis and Clean Energy, School of Environment and Science, Griffith University Xiaojun Wu State Key Laboratory of Precision and Intelligent Chemistry, School of Chemistry and Material Sciences, and Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), University of Science and Technology of China Domen Kazunari Institute of Aqua Regeneration, Shinshu University Jun Lu College of Chemical and Biological Engineering, Zhejiang University Zhi Jiang Research Center for Combustion and Environment Technology, Shanghai Jiao Tong University N-type sulfide semiconductors are promising photocatalysts due to their broad visible-light absorption, facile synthesis and chemical diversity. However, photocorrosion and limited electron transport in one-step excitation and solid-state Z-scheme systems hinder efficient overall water splitting. Liquid-phase Z-schemes offer a viable alternative, but sluggish mediator kinetics and interfacial side reactions impede their construction. Here we report a stable Z-scheme system integrating n-type CdS and BiVO₄ with a [Fe(CN)₆]³⁻/[Fe(CN)₆]⁴⁻ mediator, achieving 10.2% apparent quantum yield at 450 nm with stoichiometric H₂/O₂ evolution. High activity reflects synergies between Pt@CrOx and Co3O4 cocatalysts on CdS, and cobalt-directed facet asymmetry in BiVO₄, resulting in matched kinetics for hydrogen and oxygen evolution in a reversible mediator solution. Stability is dramatically improved through coating CdS and BiVO4 with different oxides to inhibit Fe4[Fe(CN)6]3 precipitation and deactivation by a hitherto unrecognized mechanism. Separate hydrogen and oxygen production is also demonstrated in a two-compartment reactor under visible light and ambient conditions. This work unlocks the long-sought potential of n-type sulfides for efficient, durable and safe solar-driven hydrogen production. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2211-5463 15 10 2025 Osmotic pressure‐induced calcium response states 1714 1722 EN Zidan Gao Department of Cardiovascular Physiology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiji Naruse Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Okayama Japan Masatoshi Morimatsu Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Okayama Japan Osmotic pressure is essential for maintaining cellular homeostasis; however, the mechanisms by which cells sense and respond to acute osmotic stress remain incompletely understood. Here, we applied rapid osmotic pressure stimulation to cultured HEK293T cells and observed dynamic intracellular calcium responses. Acute hypotonic stimulation evoked calcium response patterns, whereas hypertonic and isotonic stress did not elicit similar effects. Mechanistically, these calcium signals originated from the endoplasmic reticulum via ryanodine receptor 2 and propagated to neighboring cells through Connexin 43-mediated gap junctions. These findings reveal a previously unrecognized role for calcium signaling in the acute cellular response to osmotic stress, providing new insights into the mechanisms of intercellular communication during osmotic adaptation. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2304-6767 13 12 2025 Effects of miR-128-3p on Renal Inflammation in a Rat Periodontitis Model 577 EN Mohammad Nurhamim Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yixuan Zhang Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Momoko Nakahara Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daiki Fukuhara Department of Preventive Dentistry, Okayama University Hospital Yosei Nagashima Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayuki Maruyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Manabu Morita Department of Oral Health, Takarazuka University of Medical and Health Care Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: The study aim was to investigate the effects of extracellular vesicles (EVs) derived miR-128-3p on renal inflammation using a rat periodontitis model. Methods: Ten-week-old male Wistar rats were divided into two groups: a control (n = 8) and a lipopolysaccharides (LPS) group (n = 8). The LPS group received LPS (Porphyromonas gingivalis) injection in the gingiva for 7 days. At the end of the experiment, plasma, gingival tissue, and kidney samples were collected. Hematoxylin and eosin staining was performed to evaluate the glomerular tissue injury score. Bioinformatic analysis was conducted to identify potential target genes of miR-128-3p. The reverse transcription-quantitative polymerase chain reaction was performed to evaluate miR-128-3p, inflammatory, pro-inflammatory cytokine, chemokine and predicting gene’s expression. The control and LPS groups were compared using Welch’s t-test. p-values < 0.05 were considered to indicate statistical significance. Results: The kidney glomerular tissue injury score was significantly higher in the LPS than in the control group. miR-128-3p expression in the LPS group was significantly higher in the gingival tissue and plasma. mRNAs (interleukin [IL]-1β, tumor necrosis factor [TNF]-α, C-X3-C motif chemokine ligand 1 [CX3CL1], and C-X-C motif chemokine ligand 7 [CXCL7]) expression was higher in the kidney of the LPS group. The potential target genes of activin A receptor type I (Acvr1), ribosomal protein S6 kinase B1 (Rps6kb1), and transforming growth factor beta receptor type 1 (Tgfbr1) were significantly lower in the kidneys of the LPS group. Conclusions: EVs-derived miR-128-3p in LPS induced periodontitis may cause kidney inflammation which may be mediated by, Rps6kb1, Tgfbr1, and Acvr1. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2692-4609 6 1 2025 Japanese Multi‐Institution Study of Success Rates of Wire‐Guided Biliary Cannulation During Endoscopic Retrograde Cholangiopancreatography in Relation to Guidewire tip Length (JMIT Study) (With Video) e70144 EN Takeshi Ogura Endoscopy Center, Osaka Medical and Pharmaceutical University Yuki Tanisaka Gastroenterology, Saitama Medical University International Medical Center Masanari Sekine Department of Gastroenterology Jichi Medical University, Saitama Medical Center Katsumasa Kobayashi Department of Gastroenterology, Tokyo Metropolitan Bokutoh Hospital Hirotsugu Maruyama Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University Shinji Hirai Department of Medicine, Division of Gastroenterology, Kurume University School of Medicine Hideyuki Shiomi Department of Gastroenterology, Division of Hepatobiliary and Pancreatic Diseases, Hyogo Medical University Minoru Shigekawa Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine Masaki Kuwatani Department of Gastroenterology and Hepatology, Hokkaido University Hospital Kenji Ikezawa Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute Masahiro Itonaga Second Department of Internal Medicine, Wakayama Medical University Mamoru Takenaka Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University Susumu Hijioka Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital Tsukasa Ikeura Third Department of Internal Medicine, Kansai Medical University Shinpei Doi Department of Gastroenterology, Teikyo University Mizonokuchi Hospital Nao Fujimori Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University Kazuya Koizumi Department of Gastroenterology, Medicine Center, Shonan Kamakura General Hospital Yousuke Nakai Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo Tadahisa Inoue Department of Gastroenterology, Aichi Medical University Shuntaro Mukai Department of Gastroenterology and Hepatology, Tokyo Medical University Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Ryuki Minami Department of Gastroenterology, Tenri Hospital Koichiro Mandai Department of Gastroenterology, Kyoto Second Red Cross Hospital Atsuhiro Matsuda Department of Internal Medicine, Toyama Prefectural Central Hospital Takuji Iwashita First Department of Internal Medicine, Gifu University Hospital Hiroki Kawashima Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine Takao Itoi Department of Gastroenterology and Hepatology, Tokyo Medical University Objective: Wire-guided cannulation (WGC) reportedly increases the successful biliary cannulation rate and reduces the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis. Currently, various types of guidewires are available. However, the effect of the length of flexible-tip guidewires on the success rate of biliary cannulation under WGC and the rate of adverse events, especially post-endoscopic retrograde cholangiopancreatography pancreatitis, is unclear. The aim of this study was to compare the influence of long-tapered and short-tapered tips of a 0.025-inch guidewire on outcomes in primary selective biliary cannulation.<br> Methods: Consecutive patients who underwent biliary access under endoscopic retrograde cholangiopancreatography guidance using WGC at 27 high-volume centers in Japan were enrolled in this prospective registration study. The primary outcome was the technical success rate of biliary cannulation. The secondary outcomes were the rates of adverse events, biliary cannulation time, and number of guidewire insertions into the pancreatic duct.<br> Results: A total of 530 patients underwent biliary cannulation for biliary disease with native papilla between April 2021 and December 2023. The technical success rate of biliary cannulation was 86.1% (161/187) in the long-tip group and 84.3% (289/343) in the short-tip group, indicating no significant differences between the two groups. Although the frequency of post-endoscopic retrograde cholangiopancreatography was not significantly different, the successful biliary cannulation rate without guidewire mis-insertion into the main pancreatic duct was significantly higher in the long tip group (64.7%, 121/187) compared with the short tip group (54.2%, 186/343p = 0.02).<br> Conclusions: In conclusion, WGC using long-tip guidewires might reduce the risk of guidewire insertion into the main pancreatic duct. No potential conflict of interest relevant to this article was reported.

American Society of Clinical Oncology (ASCO) Acta Medica Okayama 0732-183X 2025 Amivantamab Plus Lazertinib in Atypical EGFR-Mutated Advanced Non–Small Cell Lung Cancer: Results From CHRYSALIS-2 JCO-24-02835 EN Pascale Tomasini Aix Marseille University - CNRS, INSERM, CRCM; CEPCM - AP-HM Hôpital de La Timone Yongsheng Wang Division of Thoracic Tumor Multimodality Treatment, Cancer Center and Clinical Trial Center, West China Hospital, Sichuan University Yongsheng Li Chongqing University Cancer Hospital Enriqueta Felip Medical Oncology Service, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona Lin Wu Department of Thoracic Medical Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University Jiuwei Cui The First Hospital of Jilin University Benjamin Besse Paris-Saclay University, Institut Gustave Roussy Alexander I. Spira Virginia Cancer Specialists Joel W. Neal Stanford Cancer Institute, Stanford University Koichi Goto National Cancer Center Hospital East Christina S. Baik University of Washington Fred Hutchinson Cancer Research Center Melina E. Marmarelis Perelman School of Medicine, University of Pennsylvania Eiki Ichihara Center for Clinical Oncology, Okayama University Hospital Yiping Zhang Zhejiang Cancer Hospital Jong-Seok Lee Seoul National University College of Medicine and Seoul National University Hospital Se-Hoon Lee Samsung Medical Center, Sungkyunkwan University School of Medicine James Chih-Hsin Yang National Taiwan University Cancer Center Sebastian Michels Department I for Internal Medicine, Faculty of Medicine and University Hospital Cologne, Lung Cancer Group Cologne, Center for Integrated Oncology Aachen Köln Bonn Düsseldorf, University of Cologne Zacharias Anastasiou Johnson & Johnson Joshua C. Curtin Johnson & Johnson Xuesong Lyu Johnson & Johnson Janine Mahoney Johnson & Johnson Levon Demirdjian Johnson & Johnson Craig S. Meyer Johnson & Johnson Youyi Zhang Johnson & Johnson Isabelle Leconte Johnson & Johnson Patricia Lorenzini Johnson & Johnson Roland E. Knoblauch Johnson & Johnson Leonardo Trani Johnson & Johnson Mahadi Baig Johnson & Johnson Joshua M. Bauml Johnson & Johnson Byoung Chul Cho Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine Purpose For patients with advanced non–small cell lung cancer (NSCLC) harboring atypical epidermal growth factor receptor (EGFR) mutations (eg, S768I, L861Q, G719X), efficacy of current treatment options is limited.<br> Patients and Methods CHRYSALIS-2 Cohort C enrolled participants with NSCLC harboring atypical EGFR mutations (G719X, S768I, L861Q, etc) and ≤2 previous lines of therapy. Participants were treatment-naïve or previously received first- or second-generation EGFR tyrosine kinase inhibitors. Coexisting exon 20 insertions, exon 19 deletions, or exon 21 L858R mutations were exclusionary. Participants received 1,050 mg (1,400 mg if ≥80 kg) intravenous amivantamab once weekly for the first 4 weeks and then once every 2 weeks plus 240 mg oral lazertinib once daily. The primary end point was investigator-assessed objective response rate (ORR).<br> Results As of January 12, 2024, 105 participants received amivantamab-lazertinib. Most common atypical mutations were G719X (56%), L861X (26%), and S768I (23%), including single and compound mutations. In the overall population (median follow-up: 16.1 months), the ORR was 52% (95% CI, 42 to 62). The median duration of response (mDoR) was 14.1 months (95% CI, 9.5 to 26.2). The median progression-free survival (mPFS) was 11.1 months (95% CI, 7.8 to 17.8); median overall survival (mOS) was not estimable (NE; 95% CI, 22.8 to NE). Adverse events were consistent with previous studies and primarily grade 1 and 2. Among treatment-naïve participants, the ORR was 57% (95% CI, 42 to 71). The mPFS was 19.5 months (95% CI, 11.2 to NE), the mDoR was 20.7 months (95% CI, 9.9 to NE), and mOS was NE (95% CI, 26.3 to NE). Solitary or compound EGFR mutations had no major impact on ORR. The ORR in participants with P-loop and αC-helix compressing, classical-like, and T790M-like mutations was 45% (n = 38), 64% (n = 14), and 67% (n = 3), respectively.<br> Conclusion In participants with atypical EGFR-mutated advanced NSCLC, amivantamab-lazertinib demonstrated clinically meaningful antitumor activity with no new safety signals. No potential conflict of interest relevant to this article was reported.

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

Elsevier BV Acta Medica Okayama 1078-8174 32 2 2026 Optimization of the reconstruction kernel for temporal bone imaging using photon-counting detector CT: A combined physical and visual evaluation 103274 EN S. Nishii Graduate School of Health Sciences, Okayama University T. Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Y. Morimitsu Division of Radiological Technology, Medical Support Department, Okayama University Hospital S. Kajisaki Division of Radiological Technology, Medical Support Department, Okayama University Hospital N. Akagi Division of Radiological Technology, Medical Support Department, Okayama University Hospital M. Honda Division of Radiological Technology, Medical Support Department, Okayama University Hospital H. Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University A. Sugaya Department of Otolaryngology, Head & Neck Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University K. Munetomo Department of Radiology, Medical Development Field, Okayama University F. Higaki Department of Radiology, Medical Development Field, Okayama University T. Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University T. Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Introduction: Photon-counting detector CT (PCD-CT) offers superior spatial resolution and noise characteristics compared to conventional CT. However, optimal reconstruction parameters for temporal bone imaging, especially kernel selection, remain unclear. This study aimed to identify the optimal reconstruction kernel using both objective physical image quality metrics and subjective expert assessments.<br> Methods: In phantom experiments, the system performance function (SPF) based on the task-based transfer function (TTF) and noise power spectrum (NPS) was calculated across 11 reconstruction kernels (Hr60–Hr98). Based on the results of the physical evaluation and clinical considerations from clinical practice, a subset of kernels was selected for visual assessment. For clinical images, two diagnostic radiologists evaluated three fine anatomical structures (i.e., stapes footplate, incudomalleolar joint, and cochlea) and overall image quality using both a ranking method and a 5-point Likert scale.<br> Results: TTF analysis indicated that Hr96 had the highest spatial resolution, while Hr60 showed the lowest noise in the NPS. SPF analysis identified Hr72 as providing the optimal balance between resolution and noise. Visual assessment using four reconstruction kernels (Hr60, Hr72, Hr76, and Hr84) showed that Hr76 consistently received the highest preference for overall image quality and visualization of fine structures. Statistically significant differences were observed among the kernels, with Hr60 consistently rated the lowest (p < 0.05).<br> Conclusion: The kernel Hr76 was found suitable for middle and inner ear diagnoses using PCD-CT, providing a good balance between spatial resolution and image noise. This finding provides a foundation for standardized reconstruction protocols in high-resolution temporal bone imaging.<br> Implications for practice: These findings support the use of Hr76 as a standard kernel for high-resolution temporal bone imaging and may contribute to protocol optimization in clinical PCD-CT practice. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2078-2489 16 10 2025 A Comparative Study of Authoring Performances Between In-Situ Mobile and Desktop Tools for Outdoor Location-Based Augmented Reality 908 EN Komang Candra Brata 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 Prismahardi Aji Riyantoko Department of Information and Communication Systems, Okayama University Noprianto Department of Information and Communication Systems, Okayama University Mustika Mentari Department of Information and Communication Systems, Okayama University In recent years, Location-Based Augmented Reality (LAR) systems have been increasingly implemented in various applications for tourism, navigation, education, and entertainment. Unfortunately, the LAR content creation using conventional desktop-based authoring tools has become a bottleneck, as it requires time-consuming and skilled work. Previously, we proposed an in-situ mobile authoring tool as an efficient solution to this problem by offering direct authoring interactions in real-world environments using a smartphone. Currently, the evaluation through the comparison between the proposal and conventional ones is not sufficient to show superiority, particularly in terms of interaction, authoring performance, and cognitive workload, where our tool uses 6DoF device movement for spatial input, while desktop ones rely on mouse-pointing. In this paper, we present a comparative study of authoring performances between the tools across three authoring phases: (1) Point of Interest (POI) location acquisition, (2) AR object creation, and (3) AR object registration. For the conventional tool, we adopt Unity and ARCore SDK. As a real-world application, we target the LAR content creation for pedestrian landmark annotation across campus environments at Okayama University, Japan, and Brawijaya University, Indonesia, and identify task-level bottlenecks in both tools. In our experiments, we asked 20 participants aged 22 to 35 with different LAR development experiences to complete equivalent authoring tasks in an outdoor campus environment, creating various LAR contents. We measured task completion time, phase-wise contribution, and cognitive workload using NASA-TLX. The results show that our tool made faster creations with 60% lower cognitive loads, where the desktop tool required higher mental efforts with manual data input and object verifications. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 2766-0400 5 1 2025 Linking structure and process in dendritic growth using persistent homology with energy analysis 2475735 EN Misato Tone Department of Material Science and Technology, Tokyo University of Science Shunsuke Sato Department of Material Science and Technology, Tokyo University of Science Sotaro Kunii Department of Material Science and Technology, Tokyo University of Science Ippei Obayashi Center for Artificial Intelligence and Mathematical Data Science, Okayama University Yasuaki Hiraoka Kyoto University Institute for Advanced Study, Kyoto University Yui Ogawa NTT Basic Research Laboratories, NTT Corporation Hirokazu Fukidome Research Institute of Electrical Communication, Tohoku University Alexandre Lira Foggiatto Department of Material Science and Technology, Tokyo University of Science Chiharu Mitsumata Department of Material Science and Technology, Tokyo University of Science Ryunosuke Nagaoka Department of Material Science and Technology, Tokyo University of Science Arpita Varadwaj Department of Material Science and Technology, Tokyo University of Science Iwao Matsuda Institute for Solid State Physics, The University of Tokyo Masato Kotsugi Department of Material Science and Technology, Tokyo University of Science We present a material analysis method that links structure and process in dendritic growth using explainable machine learning approaches. We employed persistent homology (PH) to quantitatively characterize the morphology of dendritic microstructures. By using interpretable machine learning with energy analysis, we established a robust relationship between structural features and Gibbs free energy. Through a detailed analysis of how Gibbs free energy evolves with morphological changes in dendrites, we uncovered specific conditions that influence the branching of dendritic structures. Moreover, energy gradient analysis based on morphological feature provides a deeper understanding of the branching mechanisms and offers a pathway to optimize thin-film growth processes. Integrating topology and free energy enables the optimization of a range of materials from fundamental research to practical applications. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 20 8 2025 Risk stratification for the prediction of skeletal-related events in patients with castration-resistant prostate cancer with bone metastases e0328792 EN Masanori Hamada Eiji Nakata Ryuichi Nakahara Shinsuke Sugihara Haruyoshi Katayama Takuto Itano Tomohiro Inoue Shota Takihira Yoshiteru Akezaki Toshifumi Ozaki Skeletal-related events (SREs) are common in patients with bone metastases from castration-resistant prostate cancer (CRPC). Despite advances in prostate cancer treatment, clinically validated predictive models for SREs in CRPC patients with bone metastases remain elusive. This gap in prognostic tools hinders optimal patient management and treatment planning for this high-risk population. This study aimed to develop a prediction model for SRE by investigating potential risk factors and classifying them into different groups. This model can be used to identify patients at high risk of SREs who need close follow-up. Between 2004 and 2013, 68 male patients with bone metastases from CRPC who were treated at our institute were evaluated for survival without SREs and survival without SREs of the spinal cord. The study analyzed clinical data at enrollment to identify risk factors for initial and spinal SREs. Multivariate analysis revealed that a high count of metastatic vertebrae, along with visceral or lymph node metastases, were significant risk factors. Patients were categorized into four subgroups based on the number of vertebral metastases and presence of visceral or lymph node metastases: 1) extensive vertebral and both types of metastases, 2) extensive vertebral without additional metastases, 3) some vertebral with other metastases, 4) some vertebral without additional metastases. The first SRE and spinal SRE occurred significantly sooner in the first subgroup compared to others. Incidence rates at 12 months for the first SRE were 56%, 40%, 27%, and 5%, and for the first spinal SRE were 47%, 40%, 27%, and 0% respectively. Patients with extensive vertebral and additional metastases require vigilant monitoring to mitigate SREs. No potential conflict of interest relevant to this article was reported.

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

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

Springer Science and Business Media LLC Acta Medica Okayama 0944-1174 60 5 2025 Diagnostic accuracy and cut-off values of serum leucine-rich alpha-2 glycoprotein for Crohn’s disease activity in the small bowel 573 582 EN Muneyori Okita Department of Biostatistics, Nagoya University Graduate School of Medicine Kento Takenaka Department of Gastroenterology and Hepatology, Institute of Science Tokyo Fumihito Hirai Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine Shinya Ashizuka Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine Hideki Iijima Osaka International Medical & Science Center, Osaka Keisatsu Hospital Shigeki Bamba Department of Fundamental Nursing, Shiga University of Medical Science Toshimitsu Fujii Department of Gastroenterology and Hepatology, Institute of Science Tokyo Kenji Watanabe Department of Internal Medicine for Inflammatory Bowel Disease, Toyama University Yosuke Shimodaira Department of Gastroenterology and Neurology, Akita University Graduate School of Medicine Hisashi Shiga Division of Gastroenterology, Tohoku University Graduate School of Medicine Sakiko Hiraoka Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toshihiro Inokuchi Research Center for Intestinal Health Science, Okayama University Takeshi Yamamura Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine Ryo Emoto Department of Biostatistics, Nagoya University Graduate School of Medicine Shigeyuki Matsui Department of Biostatistics, Nagoya University Graduate School of Medicine Background Small bowel (SB) lesions in Crohn’s disease (CD) are often asymptomatic despite being highly active. Fecal calprotectin (FC) is the most widely used biomarker of CD activity, but its drawbacks include a large intra-individual sample variability and the burden of collecting stool samples. Meanwhile, serum leucine-rich alpha-2 glycoprotein (LRG) has recently attracted attention as a biomarker that can address the limitations of FC. This study determined the diagnostic accuracy of LRG and its cut-off values for diagnosing CD activity in SB.<br> Methods This was a retrospective, multi-center study of CD patients undergoing retrograde balloon-assisted endoscopy. For ileal- and ileocolonic-type patients with a colon SES-CD score of 0, we estimated the receiver operating characteristic curve of LRG and determined the cut-off value to achieve a target sensitivity level of 80%.<br> Results Among 285 patients with SB lesions, LRG had an area under the curve (AUC) of 0.72 (95% CI 0.67–0.78) with a sensitivity of 80.2% and specificity of 47.2% for a cut-off value of 10.5 when diagnosing endoscopic remission (modified SES-CD ≤ 3), while it had an AUC of 0.72 (95% CI 0.65–0.78) with a sensitivity of 81.2% and specificity of 46.2% for a cut-off value of 10.1 when diagnosing complete ulcer healing (modified SES-CD ≤ 1).<br> Conclusion LRG was effective for diagnosing CD activity in SB, specifically with cut-off values of 10.5 and 10.1 for endoscopic remission and complete ulcer healing, respectively. A future prospective validation study will assess its clinical utility. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0041-1132 65 9 2025 Novel method for autologous peripheral blood stem cell harvest using highly concentrated sodium citrate solution replacing acid citrate dextrose solution A 1662 1672 EN Wataru Kitamura Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Department of Hematology and Oncology, Okayama University Hospital Masaya Abe Department of Hematology and Oncology, Okayama University Hospital Kazuhiro Ikeuchi Department of Hematology and Oncology, Okayama University Hospital Joji Shimono Department of Hematology and Oncology, Okayama University Hospital Kana Washio Department of Pediatrics, Okayama University Hospital Fumio Otsuka Division of Clinical Laboratory, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Background: As the processed blood volume increases, a larger amount of anticoagulant (AC) is required, which leads to a serious issue of fluid dilution in large-volume leukocytapheresis (defined as ≥3-fold total blood volume). We previously reported a novel method for allogeneic peripheral blood stem cell harvest (PBSCH) using highly concentrated sodium citrate (HSC; 5.32%), which shortened the procedure time and reduced the need for an AC solution without heparin. In this study, we extended this novel method to autologous PBSCH (auto-PBSCH) and compared it with patients who received auto-PBSCH using normal concentrated sodium citrate (NSC; 2.2%).<br> Study Design and Methods: We retrospectively analyzed consecutive auto-PBSCH data obtained using the Spectra Optia continuous mononuclear cell collection mode between May 2017 and May 2025 at our institution.<br> Results: Leukocytapheresis was performed using NSC in 36 patients and HSC in 22. In the HSC group, patients tended to be younger, had significantly lower body weight, and had significantly fewer hematopoietic tumors as primary diseases compared to the NSC group. After propensity score-matched cohort adjusted for patient background, the total amount of AC solution was significantly lower (694 [range, 77–1648] vs. 298 mL [range, 64–797], p = .02), and procedure time was significantly shorter (224 [range, 117–395] vs. 181 min [range, 103–309], p = .048) in the HSC group. Furthermore, the loss rates of magnesium and potassium were lower in the HSC group.<br> Conclusion: This novel leukocytapheresis method demonstrated the efficacy and safety in auto-PBSCH, while minimizing the patient burden. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 10 2025 Risk Stratification for the Prediction of Skeletal-Related Events in Patients With Bone Metastases From Non-small Cell Lung Cancer e95808 EN Yoshihiro Sakamoto Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eiji Nakata Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Hamada Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshimi Katayama Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Sugihara Department of Orthopedic Surgery, Shikoku Cancer Center Toshifumi Ozaki Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Skeletal-related events (SREs) frequently occur in patients with bone metastases from non-small cell lung cancer (NSCLC). This study aimed to identify risk factors for SREs in patients with NSCLC. Based on these factors, we also aimed to stratify patients into subgroups to facilitate the assessment of SRE risk. This retrospective analysis used medical records of 139 patients with NSCLC bone metastases who received treatment at our institution between 2011 and 2014. The incidence of SREs was assessed, and SRE-free survival was analyzed using the Kaplan-Meier method. Clinical information collected at registration was assessed to identify factors associated with the onset of SREs within six months. Univariate analysis was performed using Fisher’s exact test, and multivariate analysis was performed using Cox regression. Of the 139 patients, 36 (26%) developed SREs after registration. The SRE-free survival rates were 80% and 64% at 6 and 12 months, respectively. The univariate and multivariate analyses revealed that the absence of epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangement (hazard ratio (HR): 4.51, 95% confidence interval (CI): 1.32-15.7, p = 0.017) and a lactate dehydrogenase (LDH) level ≥400 U/L (HR: 8.08, 95% CI: 1.78-36.6, p = 0.0067) were risk factors for SRE presentation within six months. Patients were classified into the following three subgroups: with EGFR mutation or ALK rearrangement and LDH level <400 U/L; without EGFR mutation or ALK rearrangement and LDH level <400 U/L; with/without EGFR mutation or ALK rearrangement and LDH level ≥400 U/L. The corresponding six-month SRE-free survival rates were 92%, 69%, and 34%, respectively, showing significant differences (p < 0.001). Close monitoring is recommended for patients with LDH levels ≥400 U/L in daily clinical practice, particularly with the help of the proficiency of orthopedic and radiological experts, to prevent complications such as pathological fractures and paraplegia. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 8 2025 Conversion to Hip Arthroplasty After Internal Fixation Failure in an Intertrochanteric Femoral Fracture: A Case Report e90112 EN Shiro Fukuoka Department of Orthopedics, Kagawa Prefectural Central Hospital Tomoo Inoue Department of Orthopedics, Kagawa Prefectural Central Hospital Motoki Takahashi Department of Orthopedics, Kagawa Prefectural Central Hospital Keisuke Kawasaki Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital Toshifumi Ozaki Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Intertrochanteric femoral fractures are mainly managed by internal fixation. However, failures such as over-telescoping, cut-out, nonunion, or implant failure can occur, especially in osteoporotic elderly patients. We report the case of a patient in whom we performed artificial hip replacement surgery after fixation failure following internal fixation of an intertrochanteric femoral fracture. We report the case of an 85-year-old woman who sustained a left intertrochanteric femoral fracture treated with a dynamic hip screw (DHS). One week postoperatively, radiographs revealed over-telescoping of the lag screw. The patient did not complain of pain, but she underwent conversion to cemented bipolar hemiarthroplasty under general anesthesia. One possible cause of over-telescoping of the lag screw after surgery was that the longitudinal fracture line in the calcar of the proximal bone fragment, as seen in the initial CT image, may have extended horizontally at the neck level. During surgery, a fracture at the same site caused the anterior medial fragment to fail, resulting in a coronal shear fracture and fixation failure. When a longitudinal fracture line is observed in the calcar of the proximal fragment, it is necessary to keep in mind that it may extend horizontally at the neck level. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Vesicular Glutamate Transporter 3 Is Involved in Glutamatergic Signalling in Podocytes EN Naoko NISHII Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Accuracy of deep learning-based attenuation correction in 99mTc-GSA SPECT/CT hepatic imaging EN Masahiro MIYAI Graduate School of Health Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Factors influencing pain management practices among nurses in university hospitals in Western Japan: A cross-sectional study using hierarchical multiple regression analysis EN Mengyao XI Graduate School of Health Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

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

Acta Medica Okayama 2025 The X-ray induced quenching of the thorium-229 isomer states in a CaF2 crystal host EN Ming Guan Graduate School of Natural Science and Technology, Okayama university No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Investigating the effect of N-89 as a transdermal antimalarial drug on gametocytes of Plasmodium berghei-infected mice EN DINH THI QUYEN Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Co-precipitating calcium phosphate as oral detoxification of cadmium EN AHMAD BIKHARUDIN Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Clinical Prediction Models for Upper Airway Volume Based on Soft Palate and Airway Lumen Dimensions in Adults With Varying Vertical Skeletal Patterns EN HABUMUGISHA JANVIER Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Improving Diagnostic Performance for Head and Neck Tumors with Simple Diffusion Kurtosis Imaging and Machine Learning Bi-Parameter Analysis EN Suzuka YOSHIDA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Effects of Aged Garlic Extract on Experimental Periodontitis in Mice. EN CANYAN KUANG Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Manifestation of Headache Affecting Quality of Life in Long COVID Patients EN Kana SASAI (FUJITA) Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Impact of Lifestyle Changes on Body Weight Gain During Nationwide Lockdown Due to COVID-19 Pandemic EN Chisa NISHIDA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Genomic landscape and clinical impact of homologous recombination repair gene mutation in small bowel adenocarcinoma EN Toshiki OZATO Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Tumor microvessels with specific morphology as a prognostic factor in esophageal squamous cell carcinoma EN HNIN THIDA TUN Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Alteration of perineuronal nets and parvalbumin interneurons in prefrontal cortex and hippocampus, and correlation with blood corticosterone in activity-based anorexia model mice EN NGUYEN DUY HOANG Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Outcomes of ultra-high-pressure balloon angioplasty for congenital heart disease in single-center experience EN Maiko KONDO Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Efficacy of amivantamab, a bi-specific antibody targeting EGFR and MET, in ALK-rearranged non-small-cell lung cancer cell lines EN Tatsuya NISHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Application of intratympanic steroid injection as salvage therapy for idiopathic sudden sensorineural hearing loss EN Yasutoshi KOMATSUBARA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

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

Acta Medica Okayama 2025 Induction Therapy With Oral Tacrolimus Provides Long-Term Benefit in Thiopurine-Naïve Refractory Ulcerative Colitis Patients Despite Low Serum Albumin Levels EN Shoko IGAWA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Changes in body mass index during early childhood on school-age asthma prevalence classified by phenotypes and sex EN Toshihiko YABUUCHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Exploring factors influencing the hearing test and hearing aid adoption among Japanese older adults: Implications of recognizing the hearing loss–dementia relationship EN Ichiro FUKUMASU Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Maternal smoking during infancy increases the risk of allergic disease in children: a nationwide longitudinal survey in Japan EN Kenji SHIGEHARA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

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

Acta Medica Okayama 2025 Changes of leucine-rich alpha 2 glycoprotein could be a marker of changes of endoscopic and histologic activity of ulcerative colitis EN Yuki AOYAMA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Avoidant/restrictive food intake disorder prognosis and its relation with autism spectrum disorder in Japanese children EN Chie TANAKA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Tech Science Press Acta Medica Okayama 1851-5657 94 11 2025 Survey of Barley Sodium Transporter HvHKT1;1 Variants and Their Functional Analysis 3653 3665 EN Shahin Imran Institute of Plant Science and Resources, Okayama University Maki Katsuhara Department of Agronomy, Khulna Agricultural University Barley (Hordeum vulgare L.) employs the Na+ transporter HvHKT1;1, which is an N+-selective transporter. This study characterized the full-length HvHKT1;1 (HvHKT1;1-FL) and three mRNA variants (HvHKT1;1-V1, -V2, and -V3), which encode polypeptides of 64.7, 54.0, 40.5, and 32.9 kDa, respectively. Tissue-specific expression profiling revealed that HvHKT1;1-FL is the most abundant transcript across leaf, sheath, and root tissues under normal conditions, with the highest expression in leaves. Under 150 mM NaCl stress, HvHKT1;1-FL and its variants showed a dynamic, time-dependent expression pattern, with peak leaf expression at 2 h, sheath expression at 12 h, and root expression at 2 h, suggesting their roles in early stress response. Functional analysis using two-electrode voltage-clamp measurements demonstrated that HvHKT1;1-FL is highly selective for Na+, with minimal conductance for K+, Li+, Rb+, or Cs+. It demonstrated high Na+ transport efficiency, characterized by higher Vmax and lower Km values, while the variants showed reduced Na+ currents, lower Vmax, and higher Km values, indicating decreased Na+ transport capacity. Reversal potential analyses further confirmed Na+ selectivity, with HvHKT1;1-FL displaying the strongest preference for Na+. Notably, while all variants retained Na+ selectivity, they showed reduced efficiency, as indicated by a more negative reversal potential in low Na+ conditions. These findings highlight the functional diversity among HvHKT1;1 variants, with HvHKT1;1-FL playing a dominant role in Na+ transport. The tissue-specific regulation of these variants under salinity stress underscores their importance in barley’s adaptive responses. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1467-7881 26 11 2025 Missing the Target: A Scoping Review of the Use of Percent Weight Loss for Obesity Management e13960 EN Diana Sherifali McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University Megan Racey McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University Donna Fitzpatrick‐Lewis McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University Michelle Greenway McMaster Evidence Review and Synthesis Team; School of Nursing, McMaster University Sanjeev Sockalingam Obesity Canada Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Soo Huat Teoh Department of Clinical Medicine, Advanced Medical and Dental Institute, Universiti Sains Malaysia Ian Patton Obesity Canada David Macklin Temerty Faculty of Medicine, University of Toronto Elizabeth F. C. van Rossum Department of Internal Medicine, Division of Endocrinology, and Obesity Center CGG, Erasmus MC, University Medical Center Rotterdam Luca Busetto Department of Medicine, University of Padova Deborah Bade Horn Center of Obesity Medicine and Metabolic Performance, Department of Surgery, University of Texas McGovern Medical School J. D. Patricia Nece Obesity Action Coalition Morgan Emile Gabriel Salmon Leguede ABHispalis Spain, Alianza Hispana de Personas con Obesidad Latin America Nicole Pearce Obesity Canada Carel Le Roux School of Medicine, University College Dublin Jamy Ard School of Medicine, Wake Forest University Angela S. Alberga Department of Health, Kinesiology, and Applied Physiology, Concordia University Lee Kaplan Obesity, Metabolism and Nutrition Institute Massachusetts General Hospital and Harvard Medical School Arya M. Sharma Department of Medicine, University of Alberta Sean Wharton Temerty Faculty of Medicine, University of Toronto Introduction: To co-create comprehensive targets for obesity management, we need to understand the genesis and current use of percent weight loss targets in research. The goals of our scoping review are to (1) synthesize the literature on percent weight loss targets for adults with obesity and (2) discuss the percent weight loss targets in context with their health benefits.<br> Methods: We searched Cochrane, MEDLINE, and EMBASE for English language, pharmaceutical, and/or behavioral intervention studies in adults with obesity where the explicit aim of the study was weight reduction defined as a percent of body weight. Reviewers screened citations and extracted data including study characteristics.<br> Results: From 16,164 abstracts, we included 30 citations which were mostly randomized controlled trials (RCTs) (n = 17) or quasi-experimental studies (n = 12) published between 1992 and 2024. Most of the studies had target weight loss goals between 3% and 10% of body weight (n = 28), while n = 2 had body weight loss goals of 15% or 30%. The proportion of participants who met the percent weight loss target ranged from 5.9% (nutrition only study) to 85% (pharmaceutical study). The studies reported different reasons for targeting a percentage of weight loss such as disease-specific outcomes, reduced risk of disease, or patient-reported outcomes.<br> Conclusion: Percent weight loss targets were based on similar research and were often not feasible nor sustainable for most participants. The design of these interventions and evaluation of obesity management would benefit from more patient-focused parameters which could help to co-design comprehensive targets for research and practice. No potential conflict of interest relevant to this article was reported.

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

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

Frontiers Media SA Acta Medica Okayama 1664-3224 16 2025 A pilot transcriptomic study of a novel multitargeted BRT regimen for anti–MDA5 antibody-positive dermatomyositis: improving survival over conventional therapy 1568338 EN Moe Tokunaga Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yu Nakai Division of Rheumatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama Hospital Yoshiharu Sato DNA Chip Research Inc., Medical Laboratory Mitori Hiratsuka DNA Chip Research Inc., Medical Laboratory Yoshinori Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeshi Nakatsue Division of Rheumatology and Nephrology, Department of Internal Medicine, Nagaoka Red Cross Hospital Takako Saeki Division of Rheumatology and Nephrology, Department of Internal Medicine, Nagaoka Red Cross Hospital Takatsune Umayahara Division of Dermatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama Hospital Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinobu Koyama Division of Rheumatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama Hospital Background: Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (MDA5-DM) is associated with severe outcomes, primarily due to rapidly progressive interstitial lung disease (RP-ILD), which is often refractory to standard therapies such as calcineurin inhibitors (e.g., tacrolimus) combined with cyclophosphamide (TC-Tx). This study evaluated the efficacy of a novel multitargeted regimen combining baricitinib, rituximab, and tacrolimus (BRT-Tx) in improving survival outcomes for MDA5-DM patients with poor prognostic factors.<br> Methods: Fourteen MDA5-DM patients with multiple adverse prognostic factors were studied. Seven received the BRT-Tx regimen, and the remaining seven, previously treated with TC-Tx, served as historical controls. Twelve-month survival was assessed. Transcriptome analysis was performed for six patients (BRT=3, TC=3), beginning with cluster analysis to evaluate whether changes in peripheral blood gene expression varied according to treatment or prognosis. Gene ontology analysis characterized expression profiles in survivors and distinguished treatment effects. Alterations in the type I, II, and III interferon signatures were also assessed.<br> Results: In the TC-Tx group, four of seven patients succumbed to RP-ILD, whereas all seven BRT-Tx patients survived the 12-month observation period. Only one BRT-Tx patient required combined rescue therapies, including plasma exchange, and one case of unexplained limbic encephalitis (LE) occurred. Cytomegalovirus reactivation was observed in both groups (BRT: 5/7; TC: 6/7). Transcriptomic analysis revealed no treatment-specific clustering of differentially expressed genes (DEGs) before and after therapy. However, survivors and nonsurvivors formed distinct clusters, with survivors showing significant posttreatment suppression of B-cell-related gene expression. Moreover, interferon signature scores were significantly lower after treatment in survivors than in nonsurvivors. BRT-Tx effectively suppressed B-cell-mediated immune responses and maintained a low interferon signature, while TC-Tx resulted in nonspecific gene suppression, and in nonsurvivors, an elevated interferon signature was observed.<br> Conclusion: BRT-Tx has the potential to improve survival in MDA5-DM patients by effectively targeting hyperactive immune pathways. The combination of rituximab and tacrolimus is expected to disrupt B-cell–T-cell interactions and reduce autoantibody production, whereas baricitinib may suppress both IFN and GM-CSF signaling, regulating excessive autoimmunity mediated by cells such as macrophages. Unlike TC-Tx, BRT-Tx avoids cyclophosphamide-associated risks such as infertility and secondary malignancies. Future randomized controlled trials are warranted to validate its efficacy and safety. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 17 17 2025 Refining the Role of Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma 2770 EN Kiyofumi Takabatake Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Piao Tianyan Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuma Arashima Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Anqi Chang Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Htoo Shwe Eain Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yamin Soe Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Zin Zin Min Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masae Fujii Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University In the tumor microenvironment, various immune and stromal cells, such as fibroblasts and vascular endothelial cells, contribute to tumor growth and progression by interacting with cancer cells. Tumor-associated macrophages (TAMs) have attracted attention as major players in the tumor microenvironment. The origin of TAMs is believed to be the infiltration of monocytes derived from bone marrow progenitor cells into tumor tissues and their differentiation into macrophages, whereas tissue-resident macrophages derived from yolk sacs have recently been reported. TAMs infiltrating tumor tissues act in a tumor-promoting manner through immunosuppression, angiogenesis, and the promotion of cancer cell invasion. Reflecting the nature of TAMs, increased TAM invasion and TAM-specific gene expression in tumor tissues may be the new biomarkers for cancer. Moreover, new therapeutic strategies targeting TAMs, such as transformation into immunostimulatory macrophages, suppression of TAM infiltration, and promotion of phagocytosis, are being investigated, and many clinical trials are underway. As the origin and function of TAMs are further elucidated, TAM-targeted therapy is expected to become a new option for the immunotherapy of various cancers, including oral cancers. No potential conflict of interest relevant to this article was reported.

American Society of Hematology Acta Medica Okayama 2473-9529 9 18 2025 Refinement of day 28 treatment response criteria for acute GVHD: a collaboration study of the JSTCT and MAGIC 4640 4653 EN Yu Akahoshi Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Yoshihiro Inamoto Department of Blood and Marrow Transplantation and Cellular Therapy, Fujita Health University School of Medicine Nikolaos Spyrou Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Hideki Nakasone Division of Hematology, Jichi Medical University Saitama Medical Center Marcio A. Diniz Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Francis Ayuk Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf Hannah K. Choe Division of Hematology, Blood and Marrow Transplantation Program, The Ohio State University Comprehensive Cancer Center Noriko Doki Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Tetsuya Eto Department of Hematology, Hamanomachi Hospital Aaron M. Etra Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Elizabeth O. Hexner Department of Medicine and Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania Nobuhiro Hiramoto Department of Hematology, Kobe City Medical Center General Hospital William J. Hogan Division of Hematology, Mayo Clinic Ernst Holler Department of Hematology and Oncology, Internal Medicine III, University of Regensburg Keisuke Kataoka Division of Molecular Oncology, National Cancer Center Research Institute Toshiro Kawakita Department of Hematology, National Hospital Organization Kumamoto Medical Center Masatsugu Tanaka Department of Hematology, Kanagawa Cancer Center Takashi Tanaka Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital Naoyuki Uchida Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital Ingrid Vasova Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg and University Hospital Erlangen Satoshi Yoshihara Department of Hematology, Hyogo Medical University Hospital Fumihiko Ishimaru Technical Department, Japanese Red Cross Blood Service Headquarters Takahiro Fukuda Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital Yi-Bin Chen Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital Junya Kanda Department of Hematology, Graduate School of Medicine, Kyoto University Ryotaro Nakamura Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation James L. M. Ferrara Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Yoshinobu Kanda Division of Hematology, Jichi Medical University Saitama Medical Center John E. Levine Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Takanori Teshima Department of Hematology, Hokkaido University Faculty of Medicine and Graduate School of Medicine Overall response (OR) that combines complete (CR) and partial responses (PR) is the conventional end point for acute graft-versus-host disease (GVHD) trials. Because PR includes heterogeneous clinical presentations, reclassifying PR could produce a better end point. Patients in the primary treatment cohort from the Japanese Society for Transplantation and Cellular Therapy (JSTCT) were randomly divided into training and validation sets. In the training set, a classification and regression tree algorithm generated day 28 refined response (RR) criteria based on symptoms at treatment and day 28. We then evaluated RR for primary and second-line treatments, using the area under the receiver operating characteristic curve (AUC) and negative predictive value (NPV) for 6-month nonrelapse mortality as performance measures. RR considered patients with grade 0/1 at day 28 without additional treatment as responders. RR for primary treatment produced higher AUCs than OR with small improvement of NPVs in both validation sets: JSTCT (AUC, 0.73 vs 0.69 [P < .001]; NPV, 92.0% vs 89.6% [P < .001]) and the Mount Sinai Acute GVHD International Consortium (MAGIC; AUC, 0.71 vs 0.68 [P = .032]; NPV, 90.9% vs 89.8% [P = .009]). RR for second-line treatment produced similar AUCs but much higher NPVs than OR in both validation sets of JSTCT (AUC, 0.64 vs 0.63 [P = .775]; NPV, 74.5% vs 66.0% [P < .001]) and MAGIC (AUC, 0.67 vs 0.64 [P = .105]; NPV, 86.8% vs 76.1% [P = .004]). Classifying persistent but mild skin symptoms as responses and residual lower gastrointestinal GVHD as nonresponses were major drivers in improving the prognostic performance of RR. Our externally validated day 28 RR would serve as a better end point than conventional criteria in future first- and second-line treatment trials. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0007-1048 2025 Efficacy of ciclosporin monotherapy in non-severe aplastic anaemia not requiring transfusions: Results from a multicentre phase II study EN Ken Ishiyama Department of Hematology, Kanazawa University Hospital Masahide Yamazaki Department of Internal Medicine, Keiju Medical Center Hiroyuki Maruyama Department of Hematology, Kanazawa University Hospital Naoko Hosono Department of Hematology and Oncology, University of Fukui Hospital Hiroki Yamaguchi Department of Hematology, Nippon Medical School Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Kazuki Tanimoto Department of Hematology and Oncology, Japanese Red Cross Fukuoka Hospital Hiroyuki Sugiura Department of Hematology, Chugoku Central Hospital of Japan Mutual Aid Association of Public School Teachers Kensuke Usuki Department of Hematology, NTT Medical Center Tokyo Kenichi Yoshimura Department of Biostatistics and Health Data Science, Graduate School of Medical Science, Nagoya City University Seishi Ogawa Department of Pathology and Tumor Biology, Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University Yuzuru Kanakura Sumitomo Hospital Itaru Matsumura Department of Hematology and Rheumatology, Kindai University Faculty of Medicine Koichi Akashi Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences Shinji Nakao Department of Hematology, Kanazawa University Hospital The efficacy of ciclosporin (CsA) to treat transfusion-independent non-severe aplastic anaemia (TI-NSAA) has not yet been systematically evaluated. We conducted a prospective trial in patients with TI-NSAA treated with CsA monotherapy. CsA (3.5 mg/kg/day) was administered to patients with TI-NSAA aged ≥16. The CsA dose was adjusted to maintain a blood CsA level of ≥600 ng/mL at 2 h post-administration. Blood cell counts were assessed after 8, 16 and 52 weeks of therapy. Thirty-two evaluable patients from 21 institutions were enrolled. The median age was 63.5 (range: 16–83) years. At 8 weeks, haematological improvement, with increases in haemoglobin (Hb) ≥1.5 g/dL (haematological improvement in erythrocytes [HI-E]) and platelet count ≥30 × 109/L (haematological improvement in platelets [HI-P]), was observed in 0/25 (0%) and 6/32 (19%) evaluable cases respectively. HI-E and HI-P occurred in 1/25 (4%) and 10/32 (31%) patients at 16 weeks, respectively, and at 52 weeks in 5/25 (20%) and 16/32 (50%) patients respectively. Nine grade 3 adverse events (AEs) occurred in six patients, but there were no grade ≥4 AEs. Ten of the 32 patients experienced grade 2 renal toxicity. Low-dose CsA is effective in TI-NSAA patients and demonstrates minimal renal toxicity. However, at least 16 weeks are necessary to adequately evaluate its efficacy. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 1464-6722 26 11 2025 Comparative Genomic Analysis Identifies FleQ and GcbB as Virulence-Associated Factors in Pseudomonas syringae pv. tabaci Strains e70168 EN Muhammad Taufiq Hidayat Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kei Yoshioka Faculty of Agriculture, Okayama University Takafumi Nishimura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Shuta Asai Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sachiko Masuda Center for Sustainable Resource Science, RIKEN-TRIP Ken Shirasu Center for Sustainable Resource Science, RIKEN-TRIP Nanami Sakata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mikihiro Yamamoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiteru Noutoshi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuhiro Toyoda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuki Ichinose Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hidenori Matsui Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Pseudomonas syringae pv. tabaci (Pta) is an important plant pathogen, which causes wildfire disease in Nicotiana species. However, the genetic basis underlying strain-level differences in virulence remains largely unresolved. To address this, we performed a comparative genomic analysis between a highly virulent strain Pta6605 and a less virulent strain Pta7375. Despite high overall genome similarity, we identified key single-nucleotide polymorphisms, including premature stop-codon mutations in seven open reading frames in Pta7375. Notably, point mutations in two regulatory genes, such as fleQ, which encodes a transcription factor essential for flagellar biogenesis and biofilm formation, and gcbB, which encodes a GGDEF domain-containing diguanylate cyclase responsible for cyclic dimeric guanosine monophosphate (c-di-GMP) synthesis, were implicated in virulence disparity. Functional analyses using deletion and locus replacement mutants in the Pta6605 background revealed that the disruption of fleQ markedly reduced motility, flagellin production, c-di-GMP accumulation, biofilm formation and virulence level mirroring the Pta7375 phenotype. The gcbB replacement mutant showed reduced disease symptom development, although c-di-GMP levels remained comparable to the Pta6605 wild type. Locus replacement between strains confirmed that a point mutation in fleQ was the primary driver of reduced motility and flagellin expression in Pta7375. These findings indicate that the reduced virulence of Pta7375 is associated with impaired regulation of flagella-related genes and disruption of the FleQ-mediated c-di-GMP signalling, underscoring the value of comparative genomics in disentangling the complex regulatory networks that govern virulence in plant pathogens. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2211-1662 2025 Performance Assessment of ChatGPT for the Board Qualification Examination of the Japanese Society for Oral and Maxillofacial Radiology EN Yohei Takeshita Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyuki Kawazu Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miki Hisatomi Department of Oral and Maxillofacial Radiology, Okayama University Hospital Shunsuke Okada Department of Oral and Maxillofacial Radiology, Okayama University Hospital Mamiko Fujikura Department of Oral and Maxillofacial Radiology, Okayama University Hospital Yuri Namba Department of Oral and Maxillofacial Radiology, Okayama University Hospital Suzuka Yoshida Department of Oral and Maxillofacial Radiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Saori Yoshida Preliminary Examination Room, Okayama University Hospital Yoshinobu Yanagi Preliminary Examination Room, Okayama University Hospital Junichi Asaumi Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The aim of this study is to assess the performance and utility of ChatGPT for the board qualification examination of the Japanese Society for Oral and Maxillofacial Radiology (JSOMR). We assessed ChatGPT responses to 149 multiple-choice questions written in Japanese for the board qualification examination of the JSOMR for the 3 years from 2020 to 2022. The questions were directly entered into ChatGPT-3.5 and ChatGPT-4 models manually one by one as a prompt. The accuracy rate was calculated and classified by year, type of multiple-choice question, and level of intellectual ability, and significant differences were noted. The accuracy rate of GPT-3.5 for the 3 years was 45.0% (51.0% for 2020, 34.0% for 2021, and 50.0% for 2022), while the accuracy rate of GPT-4 was 68.5% (73.5% for 2020, 62.0% for 2021, and 70.0% for 2022) for the board qualification examination of the JSOMR. GPT-4 had a significantly higher accuracy rate than GPT-3.5 in each year. On performance classified by the type of multiple-choice questions, GPT-4 performed significantly better than GPT-3.5. However, neither model performed well with questions that required interpretation or knowledge of Japanese law. The performance of GPT-4 was significantly superior to GPT-3.5 in the board qualification examination of the JSOMR, suggesting that the use of Chat GPT, especially ChatGPT-4, would be effective as a tool for learning and preparing for the examination. No potential conflict of interest relevant to this article was reported.

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

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

Microbiology Society Acta Medica Okayama 0022-1317 106 7 2025 Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses (ICTV) from the Fungal and Protist Viruses Subcommittee, 2025 002115 EN Sead Sabanadzovic Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University Chantal Abergel Information Génomique & Structurale, UMR7256, CNRS & Aix-Marseille Université, Marseille, IMM, IM2B, IOM Marı́a A. Ayllón Departamento de Biotecnología-Biología Vegetal, Escuela Técnica Superior de Ingeniería Agronómica, Alimentaria y de Biosistemas, Universidad Politécnica de Madrid (UPM) Leticia Botella Forest Protection and Wildlife Management Mendel University in Brno Marta Canuti Department of Veterinary and Animal Sciences, University of Copenhagen Yuto Chiba School of Agriculture, Meiji University Jean-Michel Claverie Information Génomique & Structurale, UMR7256, CNRS & Aix-Marseille Université, Marseille, IMM, IM2B, IOM Robert H.A. Coutts School of Health, Medicine and Life Sciences, University of Hertfordshire Stefania Daghino Institute for Sustainable Plant Protection, National Research Council of Italy Livia Donaire Centro de Edafología y Biología Aplicada del Segura-CSIC Marco Forgia Institute for Sustainable Plant Protection, CNR Ondřej Hejna Department of Genetics and Biotechnologies, University of South Bohemia Jichun Jia College of Plant Protection, Shanxi Agricultural University Daohong Jiang College of Plant Science and Technology, Huazhong Agricultural University Ioly Kotta-Loizou School of Health, Medicine and Life Sciences, University of Hertfordshire Mart Krupovic Institut Pasteur, Université Paris Cité, CNRS UMR6047, Archaeal Virology Unit Andrew S. Lang Department of Biology, Memorial University of Newfoundland Matthieu Legendre Information Génomique & Structurale, UMR7256, CNRS & Aix-Marseille Université, Marseille, IMM, IM2B, IOM Shin-Yi Lee Marzano United States Department of Agriculture, Agricultural Research Service, Application Technology Research Unit Luca Nerva Council for Agricultural Research and Economics - Research Centre for Viticulture and Enology Judit Pénzes Department of Entomology, Texas A&M University Anna Poimala Natural Resources Institute Finland (Luke) Sofia Rigou Information Génomique & Structurale, UMR7256, CNRS & Aix-Marseille Université, Marseille, IMM, IM2B, IOM Yukiyo Sato Department of Biology, Institute for Plant Sciences, University of Cologne Wajeeha Shamsi Department of Molecular Biology and Genetics, Aarhus University Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University Massimo Turina Department of Plant Protection, School of Agriculture, The University of Jordan Syun-ichi Urayama Department of Life and Environmental Sciences, University of Tsukuba Eeva J. Vainio Natural Resources Institute Finland (Luke) Jiatao Xie College of Plant Science and Technology, Huazhong Agricultural University The Fungal and Protist Viruses Subcommittee (SC) of the International Committee on Taxonomy of Viruses (ICTV) has received a total of eight taxonomic proposals for the 2024 annual cycle. The extent of proposed changes varied, including nomenclatural updates, creation of new taxa and reorganization of established taxa. Following the ICTV procedures, all proposals were reviewed and voted upon by the members of the Executive Committee with ratification in March 2025. As a result, a total of 52 species in the families Botourmiaviridae and Marnaviridae were renamed to comply with the mandated binomial format. A new genus has been added to the dsRNA virus family Amalgaviridae, while two new families, Splipalmiviridae (Wolframvirales) and Mycoalphaviridae (Hepelivirales), were created to classify new groups of positive-sense (+) RNA mycoviruses. The class Arfiviricetes (Cressdnaviricota) was expanded by a new order Lineavirales and a new family Oomyviridae of ssDNA viruses. Additionally, a new class Orpoviricetes was created in the kingdom Orthornavirae to classify a group of bisegmented (+)RNA viruses reported from fungi and oomycetes. Finally, the order Pimascovirales was reorganized to better depict evolutionary relationships of pithoviruses and related viruses with large dsDNA genomes. The summary of updates in the taxonomy of fungal and protist viruses presented here is limited to taxa within the remit of this Subcommittee. For information on taxonomy changes on other fungal viruses closely related to animal and/or plant viruses, please see reports from sister ICTV Subcommittees (i.e. Plant Virus SC and Animal dsRNA and ssRNA(−) Viruses SC). No potential conflict of interest relevant to this article was reported.

Microbiology Society Acta Medica Okayama 0022-1317 106 7 2025 Virus taxonomy proposal summaries: a searchable and citable resource to disseminate virus taxonomy advances 002079 EN Richard Mayne Nuffield Department of Medicine, University of Oxford Peter Simmonds Nuffield Department of Medicine, University of Oxford Donald B. Smith Nuffield Department of Medicine, University of Oxford Evelien M. Adriaenssens Quadram Institute Bioscience Elliot J. Lefkowitz Department of Microbiology, University of Alabama at Birmingham Hanna M. Oksanen Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki Francisco Murilo Zerbini Departamento de Fitopatologia/BIOAGRO, Universidade Federal de Viçosa Poliane Alfenas-Zerbini Departamento de Microbiologia, Universidade Federal de Viçosa Frank O Aylward Department of Biological Sciences, Virginia Tech Juliana Freitas-Astúa Embrapa Cassava and Fruits, Cruz das Almas R. Curtis Hendrickson Department of Microbiology, University of Alabama at Birmingham Holly R. Hughes Centers for Disease Control and Prevention Mart Krupovic Institut Pasteur, Université Paris Cité, CNRS UMR6047, Archaeal Virology Unit Jens H. Kuhn Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health Małgorzata Łobocka Institute of Biochemistry and Biophysics of the Polish Academy of Sciences Arcady R. Mushegian Division of Molecular and Cellular Biosciences, National Science Foundation Judit Penzes Institute for Quantitative Biomedicine, Rutgers University Alejandro Reyes Muñoz Departamento de Ciencias Biológicas, Universidad de los Andes David L. Robertson MRC-University of Glasgow Centre for Virus Research Simon Roux Department of Energy, Joint Genome Institute, Lawrence Berkeley National Laboratory Luisa Rubino Consiglio Nazionale delle Ricerche, Istituto per la Protezione Sostenibile delle Piante, Sede Secondaria di Bari Sead Sabanadzovic Department of Agricultural Science and Plant Protection, Mississippi State University Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University Dann Turner Molecular Biology, University of the West of England Koenraad Van Doorslaer Department of Immunobiology, School of Animal and Comparative Biomedical Sciences, BIO5 Institute, University of Arizona Cancer Center Arvind Varsani The Biodesign Center for Fundamental and Applied Microbiomics, School of Life Sciences, Center for Evolution and Medicine, Arizona State University Taxonomic classification of cellular organisms requires the publication of descriptions and proposed names of species and the deposition of specimens. Virus taxonomy is developed through a different system of annual submission of formal taxonomy proposals (TPs) that can be submitted by anyone but are typically prepared by a study group appointed by the International Committee on Taxonomy of Viruses (ICTV) and consisting of experts on a particular group of viruses. These are initially evaluated by an expert subcommittee and by the executive committee (EC) of the ICTV. EC-approved TPs are then submitted for evaluation and a ratification vote by the wider ICTV membership. Following ratification, the new taxonomy is annually updated in the Master Species List, associated databases and bioinformatic resources. The process is consistent, creates traceability in assignments and supports a fully evaluated, hierarchical classification and nomenclature of all taxonomic ranks from species to realms. The structure also facilitates large-scale and coordinated changes to virus taxonomy, such as the recent introduction of a binomial species nomenclature.<br> TPs are available on the ICTV website after ratification, but they are not indexed in bibliographic databases and are not easily cited. Authors of TPs do not receive citation credit for adopted proposals, and their voluntary contributions are largely invisible in the published literature. For greater visibility of TPs and their authors, the ICTV will commence the annual publication of summaries of all TPs from each ICTV subcommittee. These summaries will provide a searchable compendium of all annual taxonomy changes and additions as well as direct links to the Master Species List and other ICTV bioinformatic resources. Their publication will provide due credit and citations for their authors, form the basis for disseminating taxonomy decisions and promote greater visibility and accessibility to taxonomy changes for the virology community. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2044-6055 15 8 2025 Neurological outcomes with hypothermia versus normothermia in patients with moderate initial illness severity following resuscitation from out-of-hospital cardiac arrest: protocol for a multicentre randomised controlled trial (R-CAST OHCA) e101809 EN Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Mitsuaki Nishikimi Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Yohei Okada Department of Preventive Services, School of Public Health, Graduate School of Medicine, Kyoto University Hiroki Maeyama Department of Emergency and Critical Care Medicine, Tsuyama Chuo Hospital Takeyuki Kiguchi Division of Trauma and Surgical Critical Care, Osaka General Medical Center Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Kazuki Nishida Department of Biostatistics, School of Public Health, Graduate School of Medicine, Kyoto University Shigeyuki Matsui Department of Biostatistics, School of Public Health, Graduate School of Medicine, Kyoto University Yasuhiro Kuroda Emergency and Critical Care Center, TMG Asaka Medical Center Kei Nishiyama Division of Emergency and Critical Care Medicine, Niigata University Graduate School of Medical and Dental Science Taku Iwami Department of Preventive Services, School of Public Health, Graduate School of Medicine, Kyoto University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences JAAM R-CAST OHCA Trial Group Introduction Temperature control is a fundamental intervention for neuroprotection following resuscitation from cardiac arrest. However, evidence regarding the efficacy of hypothermia in post-cardiac arrest syndrome (PCAS) remains unclear. Retrospective studies suggest that the clinical effectiveness of hypothermia may depend on the severity of PCAS. The R-CAST OHCA trial aims to compare the efficacy of hypothermia versus normothermia in improving 30-day neurological outcomes in patients with moderately severe PCAS following out-of-hospital cardiac arrest.<br> Methods and analysis The multicentre, single-blind, parallel-group, superiority, randomised controlled trial (RCT) is conducted with the participation of 35 emergency and critical care centres and/or intensive care units at academic and non-academic hospitals. The study enrols moderately severe PCAS patients, defined as those with a revised post-Cardiac Arrest Syndrome for induced Therapeutic Hypothermia score of 5.5–15.5. A target number of 380 participants will be enrolled. Participants are randomised to undergo either hypothermia or normothermia within 3 hours after return of spontaneous circulation. Patients in the hypothermia group are cooled and maintained at 34°C until 28 hours post-randomisation, followed by rewarming to 37°C at a rate of 0.25°C/hour. Patients in the normothermia group are maintained at normothermia (36.5°C–37.7°C). Total periods of intervention, including the cooling, maintenance and rewarming phases, will occur 40 hours after randomisation. Other treatments for PCAS can be determined by the treating physicians. The primary outcome is a favourable neurological outcome, defined as Cerebral Performance Category 1 or 2 at 30 days after randomisation and compared using an intention-to-treat analysis.<br> Ethics and dissemination This study has been approved by the Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital, Ethics Committee (approval number: R2201-001). Written informed consent is obtained from all participants or their authorised surrogates. Results will be disseminated via publications and presentations.<br> Trial registration number jRCT1062220035. No potential conflict of interest relevant to this article was reported.

Journal of Neurosurgery Publishing Group (JNSPG) Acta Medica Okayama 2694-1902 10 13 2025 Endovascular treatment for a symptomatic dissecting ophthalmic artery aneurysm occurring in the orbit: illustrative case CASE25483 EN Kohei Izumihara 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 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 Yuichi Hirata 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 Masafumi Hiramatsu 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 BACKGROUND: Peripheral ophthalmic artery aneurysms (POAAs) arising from the main trunk or branches of the ophthalmic artery (OphA) are extremely rare. However, their epidemiology and optimal management remain poorly understood. The authors report a rare case of a symptomatic POAA caused by arterial dissection that was successfully treated using endovascular therapy, leading to favorable visual recovery.<br> OBSERVATIONS: A 77-year-old woman presented with sudden-onset visual impairment in the right eye. Ophthalmological examination revealed a defect in the right visual field. CT angiography revealed a fusiform aneurysm in the right intraorbital OphA. Digital subtraction angiography revealed a pearl and string sign, consistent with a dissecting aneurysm. A balloon test occlusion (BTO) of the OphA origin confirmed collateral circulation from the external carotid artery. Internal trapping of the OphA was performed under general anesthesia. Postoperatively, the patient’s visual function gradually improved, and complete recovery was achieved within 3 months.<br> LESSONS: Although POAAs are exceptionally rare, they may lead to significant visual dysfunction owing to optic nerve compression. When visual symptoms are present, prompt intervention may reverse the symptoms. Preoperative assessment of collateral circulation using BTO is essential for treatment planning. Internal trapping may be an effective strategy when sufficient collateral flow is confirmed. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2077-0383 14 17 2025 Potential of Kidney Exchange Programs (KEPs) in Japan for Donor-Specific Antibody-Positive Kidney Transplants: A Questionnaire Survey on KEPs and a Multi-Institutional Study Conducting Virtual Cross-Matching Simulations 6122 EN Taihei Ito Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University Miki Ito Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University Naohiro Aida Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University Kei Kurihara Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University Akihiro Terao Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University Yoshihiko Watarai Department of Transplant Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital Mitsuru Saito Division of Blood Purification, Akita University Hospital Keizo Kaku Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University Daisuke Ishii Department of Urology, Kitasato University of Medicine Satoshi Sekiguchi Transplantation Surgery, Japan Community Healthcare Organization Sendai Hospital Tatsuo Yoneda Unit of Dialysis, Department of Urology, Nara Medical University Kohei Unagami Organ Transplant Medicine, Tokyo Women’s Medical University Masayuki Tasaki Division of Urology, Department of Regenerative & Transplant Medicine, Graduate School of Medical and Dental Sciences, Niigata University Hitoshi Iwamoto Department of Kidney Transplantation Surgery, Tokyo Medical University Hachioji Medical Center Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Takahashi Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of Tsukuba Kazuaki Yamanaka Department of Urology, Osaka University Graduate School of Medicine Mikio Sugimoto Department of Urology, Faculty of Medicine, Adrenal Surgery and Renal Transplantation, Kagawa University Kouhei Nishikawa Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine Chikashi Seto Department of Urology, Toyama Prefectural Central Hospital Masaki Muramatsu Department of Nephrology, Toho University Faculty of Medicine Toshihiro Asai Department of Kidney Transplant and Dialysis, Osaka City General Hospital Daiki Iwami Division of Renal Surgery and Transplantation, Department of Urology, Jichi Medical University Yasutoshi Yamada Department of Blood Purification, Kagoshima University Hospital Shigeyoshi Yamanaga Department of Transplant Surgery, Japanese Red Cross Kumamoto Hospital Tomonori Komatsu Department of Urology, Chukyo Hospital, Japan Community Healthcare Organization Masayoshi Miura Department of Renal Transplantation Surgery and Urology, Sapporo Hokuyu Hospital Takahiro Nohara Department of Urology, Kanazawa University Hospital Michihiro Maruyama Department of Frontier Surgery, Chiba University School of Medicine Yuki Miyauchi Department of Urology, Ehime University Toshiaki Tanaka Department of Urology, Sapporo Medical University Michio Nakamura Department of Transplant Surgery, Tokai University School of Medicine Kiyohiko Hotta Department of Renal and Genitourinary Surgery, Faculty of Medicine, Hokkaido University Takashi Kenmochi Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University Objectives: To clarify the need for a kidney exchange program (KEP) in Japan by conducting a questionnaire survey on KEPs and simulated KEPs by virtual cross-matching based on past cases of transplantation avoidance. Methods: In addition to the content regarding KEPs, an electronic survey was conducted to investigate the number of cases of kidney transplant abandonment due to “immunological” reasons over the past 10 years (2012–2021). Virtual cross-matching was conducted to simulate the feasibility of avoiding immunological risks and enabling kidney transplantation in patients who were previously unable to undergo the procedure. Results: The survey received responses from 107 facilities (response rate: 81.7%). In response to the question about the necessity of a KEP in Japan, 71 facilities (66.4%) indicated that KEPs are necessary. In addition, 251 living-donor kidney transplants were abandoned for “immunological” reasons over the past decade (2012–2021). Among the 80 pairs for which detailed information was available, virtual cross-matching simulations showed that 37/80 pairs (46.3%) were donor-specific antibody (DSA)-negative for blood type-matched combinations, and 41/80 pairs (51.3%) were DSA-negative for blood type-incompatible transplants. Conclusions: The need for a KEP in Japan and its potential usefulness were demonstrated. No potential conflict of interest relevant to this article was reported.

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

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

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

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

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

Wiley Acta Medica Okayama 1532-0626 37 27-28 2025 Algebraic Connectivity Maximizing Regular Graphs: Special Case Analysis and Depth‐First Search e70357 EN Masashi Kurahashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Najd Salaani Polytech Sorbonne, Sorbonne University Tsuyoshi Migita Faculty of Environmental, Life, Natural Science and Technology, Okayama University Norikazu Takahashi Faculty of Environmental, Life, Natural Science and Technology, Okayama University The algebraic connectivity is an indicator of how well connected a graph is. It also characterizes the convergence speed of some dynamic processes over networks. In this paper, taking into account that homogeneous networks are modeled as regular graphs, we tackle the following problem: given a pair (𝑛, 𝑘) of positive integers such that 𝑘 is less than 𝑛 and kn is an even number, find a 𝑘-regular graph with 𝑛 vertices that have the maximum algebraic connectivity. We first consider some special cases and derive solutions through theoretical analysis. We next present depth-first search algorithms for solving the problem, which reduce the search space by making use of some known properties of the regular graph and the algebraic connectivity.We also show the results of execution of the proposed algorithms for the values of 𝑛 up to 12. No potential conflict of interest relevant to this article was reported.

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

Wiley Acta Medica Okayama 0385-2407 52 10 2025 Biologics and Small‐Molecule Therapies in Netherton Syndrome: A Comprehensive Review 1483 1493 EN Shin Morizane Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Mukai Department of Immunology and Molecular Genetics, Kawasaki Medical School Ko Sunagawa Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken‐ichi Hasui Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Anri Morita Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hayato Nomura Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mamoru Ouchida Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Netherton syndrome (NS) is a rare congenital ichthyosis caused by loss-of-function mutations in the SPINK5 gene, leading to defective expression of the serine protease inhibitor LEKTI. Dysregulated epidermal protease activity results in impaired skin barrier function and chronic inflammation, accompanied by complex immune profiles. NS patients commonly show activation of the inflammatory axis, centered on IL-17 and IL-36, in the skin and blood, and show a psoriasis-like shift to Th17. Conversely, the immune profile differs depending on the clinical type, with ichthyosis linearis circumflexa type characterized by complement activation and Th2-type allergic responses, and scaly erythroderma type characterized by a type I IFN signature and Th9-type allergic responses. While symptomatic treatments such as emollients and topical corticosteroids have been the mainstay of care, recent advances have opened new therapeutic avenues involving biologic agents and oral small-molecule immunomodulators. This review provides a comprehensive overview of the current clinical landscape and future directions of biologics (e.g., dupilumab, secukinumab, ustekinumab) and small-molecule therapies (e.g., JAK inhibitors such as tofacitinib, baricitinib, and upadacitinib) in the treatment of NS. Though evidence remains limited to case reports and small series, preliminary data suggest that cytokine-targeted interventions—particularly those inhibiting IL-4, IL-13, IL-17, IL-36, and JAK pathways—may offer tangible clinical benefits. Well-designed clinical trials and mechanistic investigations are crucial to establishing their place in NS management. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 9 2025 Incidence and Factors Influencing Locomotive Syndrome in Cancer Patients Living in the Community e91856 EN Yoshiteru Akezaki Division of Physical Therapy, Kochi Professional University of Rehabilitation Eiji Nakata Department of Orthopaedic Surgery, Okayama University Hospital Masato Kikuuchi Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center Yoshimi Katayama Department of Rehabilitation Medicine, Okayama University Hospital Shinsuke Sugihara Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center Background Investigating locomotive syndrome (LS) of cancer survivors in the community will help clarify the importance of rehabilitation for cancer survivors in the community and provide a basis for exploring effective interventions. The primary purpose of this study was to conduct a comparison of LS, fatigue, psychological problems, and physical activity in cancer survivors and those without cancer in the community. The secondary purpose was to analyze factors influencing LS in cancer patients.<br> Methods The study involved 59 cancer patients undergoing chemotherapy at home and 59 people without cancer. The cancer patients were those undergoing chemotherapy as outpatients and constituted the cancer group. The non-cancer people were living in the community and constituted the non-cancer group.<br> Cancer and non-cancer groups were surveyed and measured for LS, fatigue, psychological problems, and physical activity. The cancer group was also surveyed for the duration of chemotherapy treatment and the presence or absence of bone metastases.<br> Results The cancer group was significantly more likely than the non-cancer group to have LS stage 2, to have fatigue, and to have psychological problems. Fatigue and psychological problems were significantly associated with LS stage 2.<br> Conclusions Cancer patients in the community need to be assessed regularly by healthcare providers and interventions should be made according to their condition. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 1439-0108 2025 Coupling effects of biochar and sediment microbial fuel cells on CH4 and CO2 emissions from straw-amended paddy soil EN Adhena Tesfau Bekele Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Morihiro Maeda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nozomi Nakahara Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ayumi Hashiguchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroaki Somura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Satoshi Akao Faculty of Science and Engineering, Doshisha University Chiyu Nakano Department of Comprehensive Technical Solutions, Okayama University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Purpose The independent incorporation of biochar and sediment microbial fuel cells (SMFCs) into paddy soil has been shown to reduce methane (CH4) emissions. However, the application of rice straw into paddy soil enhances the availability of labile carbon that stimulates methanogen growth, counteracting the mitigation effects of both methods. This study, therefore, aimed to investigate the effect of coupling biochar and SMFC on CH4 and CO2 emissions from straw-amended paddy soil.<br> Materials and methods Single chamber SMFC setups constructed using acrylic columns (height, 25 cm; inner diameter, 9 cm) with six treatments were established using soil amended with 0% (0BC), 1% (1BC), and 2% (2BC) biochar: with and without SMFC conditions. Stainless steel mesh (15 × 3 cm) and graphite felt (6 × 5 cm) were used as anode and cathode materials, respectively.<br> Results Cumulative emission of CH4 in the 0BC treatment with SMFC was 39% less than in that without SMFC. Biochar addition and SMFC operation together further reduced CH4 emission by 57% and 60% in 1BC and 2BC treatments, respectively, compared to that in the 0BC treatment without SMFC operation. The relative abundance of microbial communities indicated methane-oxidizing bacteria were enriched in the presence of biochar and hydrogenotrophic Methanoregula were suppressed by SMFC operation. This suggested that SMFC mainly inhibited CH4 production by outcompeting hydrogenotrophic archaea.<br> Conclusion The use of biochar made from leftover rice straw has an interactive effect on SMFC operation and both methods can be used to reduce CH4 emission from straw-amended paddy soil. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 2169-9313 130 10 2025 Electrical Conductivity of Carbonated Hydrous Basaltic Melt: Implications for the Conductivity Anomaly Beneath the Ocean Floors e2025JB032215 EN Bin Zhao Institute for Planetary Materials, Okayama University Jintao Zhu Institute for Planetary Materials, Okayama University Jinze He Institute for Planetary Materials, Okayama University Takashi Yoshino Institute for Planetary Materials, Okayama University We measured the electrical conductivity of CO2 and H2O-bearing basaltic melts up to 1750 K at 2 GPa, corresponding to pressure around the lithosphere-asthenosphere boundary. The electrical conductivity of the dry and hydrous samples is comparable to those reported by previous studies on the Fe-free basaltic melt. The substantial CO2 can limit the water solubility in basaltic melt at 2 GPa. Both CO2 and H2O, which cannot completely dissolve in the melt, coexist as fluid phases, resulting in reduced electrical conductivity of the basaltic melt, which has a lower water content relative to the amount of volatile components in the bulk starting system. The activation enthalpy of basaltic melt is markedly higher than those of more evolved silicate melts, especially on the H2O-poor condition, due to the more enriched alkaline earth elements. The present results suggest that an overall melt fraction of 0.1–5.3 vol% is needed to account for the high electrical conductivity anomalies (10−1.3 to 10−0.3 S/m) beneath the oceanic plate near the East Pacific Rise and Cocos plate. However, for those regions where the electrical conductivity is extremely high (≥10−0.3 S/m), more than 6 wt% H2O is expected to incorporate to maintain a melt fraction that will not trigger mechanical instability. In turn, it requires a low CO2 budget or degree of carbonation within these regions. No potential conflict of interest relevant to this article was reported.

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

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 8 2025 Subacute Progression of Gait Disturbance and Consciousness Impairment Due to Communicating Hydrocephalus Associated With Vestibular Schwannoma e89880 EN Satoka Yano Department of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Akatsuki Kubota Department of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Mizuho Kawai Department of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Daiki Yashita Department of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Wataru Satake Department of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Kaoru Yamada Department of Neuropathology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Yuki Shinya Department of Neurosurgery, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Satoru Miyawaki Department of Neurosurgery, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Takeshi Iwatsubo Department of Neuropathology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Tatsushi Toda Department of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine Patients with vestibular schwannomas (VSs) present with vestibulocochlear nerve dysfunction such as vertigo and tinnitus. VSs occasionally develop communicating hydrocephalus as a complication, which is typically characterized by an insidious progression of symptoms. We report a case of an 84-year-old female patient with a VS who developed gait disturbance and consciousness impairment over a three-week period, ultimately resulting in an inability to walk and communicate. A thorough evaluation ruled out encephalitis and other differential diagnoses. Imaging studies demonstrated findings consistent with communicating hydrocephalus, and a tap test temporarily improved her consciousness disturbances. The patient underwent ventriculoperitoneal shunting and stereotactic radiosurgery (SRS), after which both consciousness and gait disturbances dramatically improved 10 days postoperatively. The subacute development of symptoms due to normal pressure hydrocephalus associated with VSs is rare. Furthermore, to the best of our knowledge, this is the first reported case of severe gait impairment and disturbance of consciousness progressing within a short period. This case highlights the importance of considering communicating hydrocephalus associated with VSs as a differential diagnosis, even in cases of subacute consciousness disturbance. We also discuss the pathophysiology of hydrocephalus in relation to cerebrospinal fluid (CSF) clearance into the extracranial space. No potential conflict of interest relevant to this article was reported.

Springer Nature Singapore Acta Medica Okayama 1865-0929 2025 Evaluation of a Startup Program Identification for Efficient and Accurate IoT Security Investigations 417 431 EN Yuta Shimamoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Jiratchaya Phinyodom School of Engineering, Okayama University Ryota Yoshimoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyuki Uekawa NTT Social Informatics Laboratories Mitsuaki Akiyama NTT Social Informatics Laboratories Toshihiro Yamauchi Faculty of Environmental, Life, Natural Science and Technology, Okayama University Not all file in firmware are executed while using Internet of Things (IoT) devices and hundreds to approximately a thousand executable and linkable format files exist in one firmware. Therefore, security investigations without prioritization may lead to investigate programs that are not executed while using IoT devices first. This has resulted in inefficient security investigations. To perform efficient security investigations, we proposed a method that can identify programs executed during the startup process. However, only two firmware were used for the evaluation which can only evaluate one of the two startup sequences in the OpenWrt-based firmware. In addition, security investigations to validate whether the proposed method addresses the problem of inefficient security investigations were limited to OpenWrt-based firmware. In this study, we use more firmware data for evaluation and validation. We use nine firmware not used in previous studies including startup methods that have not previously been used for evaluation. In addition, we increase the number of firmware used for validation to 225. The evaluation results demonstrate that the proposed method can identify with only few false positives. The validation demonstrates that efficiency can be improved and prioritizing investigations by considering the proposed method result is worthwhile. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 10 2025 Primary Lacrimal Sac Diffuse Large B-cell Lymphoma Treated With Local Radiotherapy Alone: A Case With No Relapse After 21 Years of Follow-Up e95411 EN Toshihiko Matsuo Healthcare Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takehiro Tanaka Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Mitsuhiro Takemoto Radiotherapy, Himeji Red Cross Hospital Primary lacrimal sac lymphoma is rare and diagnosed as diffuse large B-cell lymphoma in a predominant histopathological type. Systemic chemotherapy would be the standard of care, but local radiotherapy may be a treatment option toward a localized lesion. The present patient is a 54-year-old otherwise healthy woman with a right lacrimal sac mass, which was proven by excisional biopsy to be diffuse large B-cell lymphoma. Since she did not have any other systemic lesions on gallium scintigraphy and neck-to-abdominal computed tomography scans, which were the standard procedure at that time, she underwent local radiotherapy at 40 Gy. Two years later, at the age of 56 years, she developed radiation retinopathy with macular edema in the right eye and had spotty laser photocoagulation in the nasal half of the fundus. At the age of 57 years, she developed radiation cataract and underwent cataract surgery with intraocular lens implantation in the right eye. At the age of 58 years, the macular edema in the right eye became worse and remained active, resulting in poor visual acuity of 0.1. She thus underwent 25-gauge vitrectomy in the right eye to peel off the adhering posterior vitreous surface, together with the internal limiting membrane, as the standard procedure at that time. The visual acuity in the right eye was elevated to 0.6. She maintained the visual acuity afterward and had no relapse of lymphoma in 21 years from the diagnosis of primary right lacrimal sac diffuse large B-cell lymphoma. Local radiotherapy would still be a treatment option for localized lymphoma lesions such as primary lacrimal sac lymphoma. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 26 20 2025 Neurofibromin Encoded by the Neurofibromatosis Type 1 (NF1) Gene Promotes the Membrane Translocation of SPRED2, Thereby Inhibiting the ERK Pathway in Breast Cancer Cells 10072 EN Nang Thee Su Pwint Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chunning Li Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tong Gao Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuze Wang Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masakiyo Sakaguchi Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Neurofibromin (NF) inhibits the RAS/RAF/ERK pathway through its interaction with SPRED1 (Sprouty-related EVH1 domain-containing protein 1). Here, we investigated the functional relationship between NF and SPRED2 in breast cancer (BC). Human BC cell lines were transfected to downregulate or overexpress NF and SPRED2 and subsequently subjected to functional assays. Protein and mRNA levels were analyzed by Western blotting and RT-qPCR, respectively. Protein–protein interactions were examined by immunoprecipitation. Database analyses and immunohistochemistry (IHC) of BC tissues were performed to validate the in vitro findings. Downregulating NF or SPRED2 expression in BC cells enhanced cell proliferation, migration and invasion accompanied by RAF/ERK activation, whereas overexpression produced opposite effects. NF formed a protein complex with SPRED2 and facilitated its translocation to the plasma membrane. By IHC, SPRED2 membrane localization was absent in NF-negative luminal A and triple-negative BC (TNBC) but present in a subset of luminal A BC. By database analyses, both NF1 and SPRED2 mRNA levels were reduced in BC tissues, and luminal A BC patients with high expression of both NF1 and SPRED2 mRNA exhibited improved relapse-free survival. These results suggest a critical role for the NF–SPRED2 axis in BC progression and highlight it as a potential therapeutic target. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 17 20 2025 Impact of Neoadjuvant Chemotherapy with Gemcitabine Plus S-1 in Patients with Resectable Pancreatic Ductal Adenocarcinoma 3287 EN Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomokazu Fuji 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 Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Yuki Fujii 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 Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Objectives: Although neoadjuvant chemotherapy (NAC) is not universally recommended for resectable pancreatic ductal adenocarcinoma (PDAC), NAC with gemcitabine plus S-1 (NAC-GS) has become a commonly used regimen for resectable PDAC in Japan. Furthermore, the impact of achieving textbook outcomes (TO) in patients receiving NAC-GS remains unclear. Methods: This retrospective study included 265 patients who were diagnosed with resectable PDAC at our institution between January 2009 and December 2023. Patients were categorized into two groups: the NAC-GS group (n = 81; 2019–2023) and the upfront surgery (UFS) group (n = 164; 2009–2018). After comparing the clinical outcomes between groups, multivariate analyses for survival were performed. Additionally, outcomes stratified by the achievement of the modified TO were analyzed in the NAC-GS group. Results: The completion rate of NAC-GS was 90.1%. Patients in the NAC-GS group exhibited significantly longer survival than those in the UFS group (2-year recurrence-free survival: 61.4% vs. 37.9%, p < 0.01; 2-year overall survival: 83.2% vs. 61.2%, p < 0.01). Multivariate analyses identified lymph node metastasis, NAC-GS induction, and completion of adjuvant chemotherapy as factors significantly associated with improved survival. Moreover, among patients who received NAC-GS, those who achieved modified TO demonstrated significantly longer survival than those who did not. Conclusions: This study demonstrated the clinical efficacy of NAC-GS in patients with resectable PDAC. Induction of NAC-GS was significantly associated with improved long-term outcomes. In multidisciplinary treatment strategies for PDAC, achieving a modified TO may lead to improved survival of patients undergoing NAC-GS. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0921-8831 36 10 2025 Evaluating the effects of electrolytes on the interaction forces between alumina surfaces in polyacrylic acid solutions using atomic force microscopy 105028 EN Naoto Kishimoto Graduate School of Natural Science and Technology, Okayama University Ryota Kaji Faculty of Science and Engineering, Doshisha University Katsumi Tsuchiya Faculty of Science and Engineering, Doshisha University Koreyoshi Imamura Graduate School of Natural Science and Technology, Okayama University Naoyuki Ishida Faculty of Science and Engineering, Doshisha University Evaluation and control of ceramic slurry at the microscopic level are critical to ensure consistent quality in manufactured ceramics. Notably, metal ions such as Mg2+ and Al3+ are common in ceramic slurries and significantly influence the stability of particle. This study applied atomic force microscopy to investigate the interaction forces between alumina particle surfaces in the presence of different concentrations of three metal ions and polyacrylic acid (PAA), a widely used dispersant.<br> The attractive forces observed at low PAA concentrations were attributed to polymer bridging between alumina surfaces, whereas the repulsive forces observed at high PAA concentrations were attributed to the domination of steric repulsion between adsorbed PAA molecules. The presence of multivalent metal ions, such as Mg2+ and Al3+, modulated these interactions; an increasing ion valence induced a transition from repulsive to attractive force, primarily owing to electrostatic screening, which caused conformational collapse of the PAA chains and diminished the range of steric repulsion. Similarly, increasing the concentration of these metal ions decreased the range of repulsive forces, eventually resulting in a net attraction driven by the same electrostatic and polymer conformation mechanisms. Notably, the addition of 0.1 M AlCl3 produced an anomalous long-range attraction between surfaces that could not be explained by conventional mechanisms, such as polymer bridging or electrostatic interactions between charge domains. No potential conflict of interest relevant to this article was reported.

The Royal Society Acta Medica Okayama 2054-5703 12 9 2025 On weapons allometry and the form of sexual selection 251152 EN Hironori Shinohara Center for Ecology and Conservation, University of Exeter, Cornwall Campus Manmohan D. Sharma Center for Ecology and Conservation, University of Exeter, Cornwall Campus Tanya M. Pennell Center for Ecology and Conservation, University of Exeter, Cornwall Campus Kensuke Okada Faculty of Environmental, Life, Natural Science and Technology, Okayama University David J. Hosken Center for Ecology and Conservation, University of Exeter, Cornwall Campus The study of trait scaling with body size (allometry) has a long history, and it has been argued that positive static allometry is an indicator of directional sexual selection. However, a range of allometries exists for sexually selected traits, and modelling shows this variation can be generated by altering the form of selection (fitness functions) on the trait and/or body size. Interestingly, in all models, positive allometry appears to emerge only when there is directional selection on trait size. Here, we report on a sexually selected trait that shows strong positive static allometry and yet appears to be under stabilizing selection. This surprising finding suggests the evolution of trait scaling is even more nuanced than currently appreciated. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Gastroduodenal Artery-Preserving Pancreatoduodenectomy after Esophagectomy with Gastric Conduit Reconstruction 393 398 EN Akari Masunaga Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motohiko Yamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeyoshi Nishiyama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriyuki Kanehira Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yumi Sota Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/69441 Pancreatoduodenectomy (PD) after esophagectomy with gastric conduit reconstruction is technically challenging. Preserving the blood supply of the gastric conduit is crucial in performing PD after esophagectomy. We report the case of a 66-year-old man who underwent gastroduodenal artery-preserving PD after esophagectomy with gastric conduit reconstruction for intraductal papillary mucinous neoplasm. The patient developed pseudoaneurysm rupture postoperatively, but was successfully treated with interventional radiology. Precise assessment is important in developing a surgical strategy depending on the patient’s specific anatomy and tumor characteristics. Moreover, special attention should be paid to avoid accidental injuries of the gastric conduit and gastric vessels during surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 The Utility of a Preoperative 3D Imaging Analysis System for Trigonal Meningioma 387 392 EN Yusuke Mori Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiro Otani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Omae Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuichiro Hirano Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Joji Ishida Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Fujii Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Haruma 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 Toshi Matsushita Division of Radiological Technology, Okayama University Hospital Fumiyo Higaki Department of Radiology, Medical Development Field, Okayama University 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 Case Report 10.18926/AMO/69440 Trigonal meningiomas are rare and pose surgical challenges due to their deep location and proximity to critical neuroanatomical structures. We present the case of a 67-year-old woman with a growing trigonal meningioma successfully resected with guidance by a preoperative 3D imaging analysis system. Integration of CT and MRI including diffusion tensor imaging (DTI) enabled precise mapping of the optic radiation, guiding a middle temporal gyrus approach. Preoperative embolization reduced tumor vascularity, facilitating gross total resection with minimal blood loss. This case highlights the effectiveness of preoperative 3D imaging systems in optimizing surgical planning and improving outcomes in complex neurosurgical cases. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Immunoglobulin G4-related Disease Mimicking Portal Vein Tumor Thrombus 381 385 EN Atsunobu Sakurai Department of Radiology, NHO Iwakuni Clinical Center Takayuki Yabuki Department of Radiology, NHO Iwakuni Clinical Center Hideki Aoki Department of Gastroenterological Surgery, NHO Iwakuni Clinical Center Akiko Iseki Department of Pathology, NHO Iwakuni Clinical Center Case Report 10.18926/AMO/69439 We report the case of a 72-year-old Japanese man with an incidental portal vein mass that was surgically resected and diagnosed as immunoglobulin G4 (IgG4)-related disease. The mass was discovered during an atrial fibrillation examination. The patient had a history of gastric cancer and was also diagnosed with rectal cancer, raising concerns about metastasis. Due to technical challenges, a biopsy was not feasible. Imaging findings suggested portal vein tumor thrombosis, complicating the diagnosis. This case highlights a rare presentation of IgG4-related disease mimicking portal vein tumor thrombus. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Blood Pressure and Heart Rate Patterns Identified by Unsupervised Machine Learning and Their Associations with Subclinical Cerebral and Renal Damage in a Japanese Community: The Masuda Study 369 379 EN Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Minako Kinuta Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sosuke Munetomo Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mari Fukuda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuhide Kojima Department of Radiology, Okayama University Hospital Kaori Taniguchi Department of Environmental Medicine and Public Health, Izumo, Shimane University Faculty of Medicine Noriko Nakahata Department of Health and Nutrition, The University of Shimane Faculty of Nursing and Nutrition Hideyuki Kanda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/69438 We applied unsupervised machine learning to analyze blood pressure (BP) and resting heart rate (HR) patterns measured during a 1-year period to assess their cross-sectional relationships with subclinical cerebral and renal target damage. Dimension reduction via uniform manifold approximation and projection, followed by K-means++ clustering, was used to categorize 362 community-dwelling participants (mean age, 56.2 years; 54.9% women) into three groups: Low BP and Low HR (Lo-BP/Lo-HR), High BP and High HR (Hi-BP/Hi-HR), and Low BP and High HR (Lo-BP/Hi-HR). Cerebral vessel lesions were defined as the presence of at least one of the following magnetic resonance imaging findings: lacunar infarcts, white matter hyperintensities, cerebral microbleeds, or intracranial artery stenosis. A high urinary albumin-to-creatinine ratio (UACR) was defined as the top 10% (≥ 12 mg/g) of the mean value from ≥2 measurements. Poisson regression with robust error variance, adjusted for demographics, lifestyle, and medical history, showed that the Hi-BP/Hi-HR group had relative risks of 3.62 (95% confidence interval, 1.75-7.46) for cerebral vessel lesions and 3.58 (1.33-9.67) for high UACR, and the Lo-BP/Hi-HR group had a relative risk of 3.09 (1.12-8.57) for high UACR, compared with the Lo-BP/Lo-HR group. These findings demonstrate the utility of an unsupervised, data-driven approach for identifying physiological patterns associated with subclinical target organ damage. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Comparison of Extraocular Muscles in Patients with Exotropia and Healthy Participants Using Anterior Segment Optical Coherence Tomography 353 358 EN Yuki Chihara Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ichiro Hamasaki Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kiyo Shibata Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Morisawa Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Reika Kono Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keisuke Kanenaga Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/69436 To analyze and characterize the medial and lateral rectus muscles in patients with exotropia using anterior segment optical coherence tomography (AS-OCT). This study included 24 patients with exotropia (48 eyes) and 25 healthy individuals (50 eyes). Anterior segment optical coherence tomography was used to construct the en face images. The anterior chamber angle to the extraocular muscle insertion distance, muscle width, and muscle fiber angle from the muscle insertion sites were compared between the exotropia and the control groups. The correlation between these parameters and age or angle of deviation was evaluated. The mean ages were 13.2±4.1 years for the exotropia group and 17.6±7.2 years for the control group. The lateral rectus angle was significantly more inwardly rotated in the exotropia group than in the control group (1.6±6.3°, −1.4±4.0°, p=0.014). With increasing angle of deviation, the width of the lateral rectus increased (p=0.002). Our results indicate that the lateral rectus angle is significantly more inwardly rotated in patients with exotropia. These findings should contribute to a deeper understanding of the extraocular muscles in patients with this condition. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Evaluation of Scleral Adjustment Method: A Novel Adjustable Suture Technique in Strabismus Surgery 339 343 EN Ichiro Hamasaki Lino Eye Clinic Kiyo Shibata Lino Eye Clinic Original Article 10.18926/AMO/69434 To determine whether passing a pole suture through the sclera at two points provides fixation comparable to that of a sliding noose, we measured the tensile strength of the suture‒sclera interface during simulated traction. In this in vitro study, three suture patterns were evaluated in porcine eyeballs, using 6-0 polyglycolic acid sutures. Patterns A (control), B (second suture pass perpendicular), and C (second suture pass in the same direction) were compared. The tensile strength of each pattern was measured 20 times using a KANON TK300CN, and the results were analyzed using the Kruskal‒Wallis test. Pattern A showed a tensile strength of 2±4 gram-force (gf) (range: 0-12). Pattern B showed 112±38 gf (range: 61-184). Pattern C showed 139±31 gf (range: 97-204). Patterns B and C had significantly higher tensile strengths than Pattern A (p<0.001). Although Pattern C was not significantly different from Pattern B (p=0.363), it exhibited the highest tensile strength. Lifting the suture between the first and second suture passes allows for an adjustable suture length, suggesting that adjustability can be achieved using only the sclera. This scleral adjustment method with a second suture pass offers a durable means of securing extraocular muscles and may represent a valuable addition to adjustable suturing techniques. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Current Status of Extracorporeal Membrane Oxygenation as a Treatment Strategy for Primary Graft Dysfunction after Lung Transplantation 329 337 EN Kei Matsubara Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Kentaroh Miyoshi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/69433 Primary graft dysfunction (PGD) is one of the major risk factors affecting patients’ short- and long-term survival after lung transplantation. No particular management strategy has been established for PGD; supportive care is the mainstay of PGD treatment. When a supportive strategy fails, the patient may require the introduction of extracorporeal membrane oxygenation (ECMO) as the last-resort measure for severe PGD. A variety of study of ECMO as a PGD treatment was reported and the management of PGD patients developed so far. Early recognition of a patient’s need for ECMO and its prompt initiation are critical to improved outcomes. The use of venovenous-ECMO became the preferred procedure for PGD rather than venoarterial-ECMO. However, the current ECMO strategy has limitations, and using ECMO to manage patients with PGD is not sufficiently effective. Further studies are required to develop this promising technology. No potential conflict of interest relevant to this article was reported.